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Yacoub H, Zenzri Y, Cherif D, Ben Mansour H, Attia N, Mokrani C, Ben Zid K, Letaief F, Maamouri N, Mezlini A. Predictors of pathological complete response after total neoadjuvant treatment using short course radiotherapy for locally advanced rectal cancer. BMC Gastroenterol 2025; 25:208. [PMID: 40165151 PMCID: PMC11956259 DOI: 10.1186/s12876-025-03709-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 02/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Total neoadjuvant treatment (TNT) has become a standard treatment approach for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following TNT have better outcomes (overall survival, relapse free survival). However, not all patients treated for LARC with neoadjuvant treatment achieve pCR. AIM The aim of our study was to assess the rate and predictors of pCR. MATERIALS AND METHODS We performed a retrospective study at medical oncology unit in a tertiary care teaching hospital. All consecutive LARC patients without any evidence of distant metastasis who underwent neoadjuvant chemoradiotherapy and surgery between June 2020 and January 2023 were included in the research. Pathological response to neoadjuvant treatment was assessed using Mandard grading system and response was categorized as pCR or not‑pCR. Two different standardized protocols for the neoadjuvant treatment were used: the first group was treated with induction chemotherapy followed by short course radiotherapy and the second group was treated with the RAPIDO protocol. Correlation between different studied parameters and pCR was determined using univariate and multivariate logistic regression analysis. RESULTS The mean age of the 91 included patients (46 men and 45 women) was 58.53 ± 10.3 years. Twenty (22%) were found to have a pCR (Mandard TRG1) in the operative specimen. In univariate analysis, patients less than 60 years, continuation of chemotherapy and patients treated with the induction chemotherapy followed by short course radiotherapy showed a better pCR as compared to patients treated with Rapido protocol (p = 0.043, p = 0.0001 and p = 0.021 respectively). Patients with mucinous component had low pCR rates (p = 0.021). On logistic regression analysis, chemotherapy continuation (OR = 10.27, 95% CI = 2,14-49.32), and absence of mucinous component (OR = 12.6, 95% CI = 3.1-40.32) were significant predictors of pCR. The median survival was 37.7 months. CONCLUSION Mucinous component and chemotherapy interruption are associated with lower pCR rates. Integrating these factors into personalized treatment algorithms may help optimize therapeutic strategies and improve outcomes for patients with LARC.
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Affiliation(s)
- Haythem Yacoub
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia.
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia.
| | - Yosr Zenzri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Dhouha Cherif
- Gastroenterolgy department, La Rabta Hospital, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Hajer Ben Mansour
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Najla Attia
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Cyrine Mokrani
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Khadija Ben Zid
- Radiotherapy department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Feryel Letaief
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Nadia Maamouri
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
| | - Amel Mezlini
- Oncology department, Salah Azaiez Institute, Tunis, Tunisia
- Faculty of Medicine of Tunis, El Manar university, Tunis, Tunisia
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Jehaes C, Panis Y, Fernandez L, Lelong B, Julião GS, Vailati B, Lefevre JH, Tuech JJ, Azevedo J, Benoist S, Parvaiz A, Diane M, Gama AH, Perez R, Denost Q. Risk of distant metastasis after local excision for near-complete response versus salvage surgery for local regrowth in rectal cancer: Results from an international registry. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109761. [PMID: 40133029 DOI: 10.1016/j.ejso.2025.109761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 02/05/2025] [Accepted: 03/09/2025] [Indexed: 03/27/2025]
Abstract
AIM Watch and Wait (WW) strategy is currently used for mid/low rectal adenocarcinoma after neoadjuvant treatment (NAT). Local regrowth (LR) is a well-known risk, but its impact on distant metastasis (DM) is increasingly debated. This study aimed to assess the rate of DM after local excision (LE) for near-complete clinical response (ncCR) at restaging versus salvage surgery for regrowth following WW. METHOD Retrospective analysis of DM rates from a prospective international registry, comparing patients with ncCR after NAT who underwent LE and patients with initial complete clinical response (cCR) and WW strategy, who underwent salvage surgery for regrowth. The primary endpoint was the 5-year distant metastasis-free survival (5y-DMFS). Univariate/Multivariate analysis were performed to identify risk factors of DM. RESULTS Among 138 patients included, 59 had LE for ncCR and 79 had salvage surgery after regrowth including TME (n = 23), APR (n = 30) and LE (n = 26). The 5y-DMFS was lower in patients with surgery at regrowth, 71 % vs. 93 % (p = 0.006). LR was the only independent risk factor associated with DM (OR:3.89; 95 % CI:1.34-11.25; p = 0.012). When only patients managed by salvage LE for LR are considered, 5y-DMFS was equivalent to LE at restaging (87 vs. 93; p = 0.442). CONCLUSION Patients with rectal cancer undergoing LE for ncCR after NAT have a significantly lower rate of DM compared to patients undergoing salvage surgery after LR within WW approach. Patients managed by LE for regrowth may represent a distinct subgroup where the risk of subsequent DM is equivalent to patients managed by LE at restage.
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Affiliation(s)
- Constance Jehaes
- Bordeaux Colorectal Institute, Clinique Tivoli-Ducos, Bordeaux, France
| | - Yves Panis
- Department of Digestive Surgery, Groupe Hospitalier Privé Ambroise Paré - Hartmann, Neuilly-Sur-Seine, France
| | - Laura Fernandez
- Colorectal Surgery, Digestive Department, Fundacao Champalimaud, Lisbon, Portugal
| | - Bernard Lelong
- Department of Digestive Surgical Oncology, Institut Paoli Calmettes, Marseille, France
| | - Guilherme Sao Julião
- Colorectal Surgery Division, Angelita and Joaquim Gama Institute, Brazil; Department of Surgical Oncology, Colorectal Surgery Division, Hospital Beneficencia Portuguesa, Sao Paulo, Brazil; Colorectal Surgery Division, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - Bruna Vailati
- Colorectal Surgery Division, Angelita and Joaquim Gama Institute, Brazil; Department of Surgical Oncology, Colorectal Surgery Division, Hospital Beneficencia Portuguesa, Sao Paulo, Brazil; Colorectal Surgery Division, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
| | - Jeremie H Lefevre
- Department of Digestive Surgery, Sorbonne University, AP-HP, Hôpital Saint Antoine, Paris, France
| | - Jean-Jacques Tuech
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - José Azevedo
- General Surgery, Hospital da Horta EPER, Horta, Portugal
| | - Stéphane Benoist
- Department of Digestive Oncological Surgery, AP-HP CHU Bicêtre, Paris, France
| | - Amjad Parvaiz
- Digestive Surgery Unit, Colorectal Division, Fundacao Champalimaud, Lisbon, Portugal
| | - Mege Diane
- Department of Surgical Oncology, AP-HM Timone Hospital, Marseille, France
| | - Angelita Habr- Gama
- Colorectal Surgery Division, Angelita and Joaquim Gama Institute, Brazil; Colorectal Surgery Division, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
| | - Rodrigo Perez
- Colorectal Surgery Division, Angelita and Joaquim Gama Institute, Brazil; Department of Surgical Oncology, Colorectal Surgery Division, Hospital Beneficencia Portuguesa, Sao Paulo, Brazil; Colorectal Surgery Division, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
| | - Quentin Denost
- Bordeaux Colorectal Institute, Clinique Tivoli-Ducos, Bordeaux, France.
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Ouyang K, Yang Z, Yang Y, Lyu Z, Wang J, Li Y. Effectiveness of Organ Preservation for Locally Advanced Rectal Cancer With Complete Clinical Response After Neoadjuvant Chemoradiotherapy: Bayesian Network Meta-analysis. Dis Colon Rectum 2025; 68:287-298. [PMID: 39638637 DOI: 10.1097/dcr.0000000000003484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy followed by radical surgery is the common treatment for patients with locally advanced rectal cancer. Presently, for patients with complete clinical response after neoadjuvant chemoradiotherapy, organ preservation ("watch-and-wait" and local excision strategies) has been increasingly favored. However, the optimal treatment for patients with complete clinical response remains unclear. OBJECTIVE This study aimed to use Bayesian meta-analysis to determine the best treatment for patients with locally advanced rectal cancer with complete clinical response among radical surgery, local excision, and watch-and-wait strategies. DATA SOURCES PubMed, Web of Science, Cochrane Library, and Embase (Ovid) databases were searched for literature published through December 31, 2023. STUDY SELECTION Studies that compared 2 or more treatments for patients with complete clinical response were included. INTERVENTION The analysis was completed via Bayesian meta-analysis using a random-effects model. MAIN OUTCOME MEASURES Surgery-related complications, local recurrence, distant metastasis, and 5-year overall and disease-free survival rates. RESULTS Eleven articles met the inclusion criteria. The watch-and-wait group and local excision group exhibited a higher rate of tumor recurrence compared to the radical surgery group (watch-and-wait vs radical surgery: OR, 9.10 [95% CI, 3.30-32.3]; local excision vs radical surgery: OR, 2.93 [95% CI, 1.05-9.95]). The distant metastasis, overall survival, and disease-free survival rates of the 3 treatments were not statistically different. The radical surgery group had the most number of stomas and had the greatest risk of morbidity than the watch-and-wait group (watch-and-wait vs radical surgery: OR, 0.00 [95% CI, 0.00-0.12]). LIMITATIONS The study included only 1 randomized controlled trial compared to 10 observational studies, which could affect overall quality. Funnel plots of disease-free survival rates and stoma suggest significant publication bias among studies that compared radical surgery with the watch-and-wait strategy. CONCLUSIONS The watch-and-wait strategy could be optimal for patients with locally advanced rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy.
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Affiliation(s)
- Kaibo Ouyang
- Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Zifeng Yang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Yuesheng Yang
- Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Zejian Lyu
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Junjiang Wang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Yong Li
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
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Williams H, Lee C, Garcia-Aguilar J. Nonoperative management of rectal cancer. Front Oncol 2024; 14:1477510. [PMID: 39711959 PMCID: PMC11659252 DOI: 10.3389/fonc.2024.1477510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/21/2024] [Indexed: 12/24/2024] Open
Abstract
The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited. Challenges remain in optimizing multimodal treatment regimens to maximize tumor regression and in improving the accuracy of patient selection for WW. This review summarizes the history of treatment for rectal cancer and the development of a WW strategy. It also provides an overview of clinical considerations for patients interested in nonoperative management, including restaging strategies, WW selection criteria, surveillance protocols and long-term oncologic outcomes.
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Affiliation(s)
| | | | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer
Center, New York, NY, United States
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5
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Yang Z, Ma J, Han J, Li A, Liu G, Sun Y, Zheng J, Zhang J, Chen G, Xu R, Sun L, Meng C, Gao J, Bai Z, Deng W, Zhang C, Su J, Yao H, Zhang Z. Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer. MED 2024; 5:1293-1306.e4. [PMID: 39047732 DOI: 10.1016/j.medj.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 02/18/2024] [Accepted: 07/01/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT). METHODS This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT. FINDINGS A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort. CONCLUSIONS Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC. FUNDING This research was funded by the China National Natural Science Foundation (82202884).
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Affiliation(s)
- Zhengyang Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jingxin Ma
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jiagang Han
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ang Li
- Department of General Surgery, Beijing Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Gang Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi Sun
- Department of Anorectal, Tianjin People's Hospital, Tianjin, China
| | - Jianyong Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Air Force Medical University, Xi'an, China
| | - Jie Zhang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guangyong Chen
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Rui Xu
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Liting Sun
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Cong Meng
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jiale Gao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Zhigang Bai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Wei Deng
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Chenlin Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jianrong Su
- Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China.
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China.
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Rizzo G, Amodio LE, D'Annibale G, Marzi F, Quero G, Menghi R, Tondolo V. Nonoperative management and local excision after neoadjuvant chemoradiation therapy for rectal cancer. Minerva Surg 2024; 79:470-480. [PMID: 38953759 DOI: 10.23736/s2724-5691.24.10445-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.
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Affiliation(s)
- Gianluca Rizzo
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy -
| | - Luca E Amodio
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giorgio D'Annibale
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Federica Marzi
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giuseppe Quero
- Unit of Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Roberta Menghi
- Unit of Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Tondolo
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
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7
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Spolverato G, Bao QR, Delrio P, Guerrieri M, Ortenzi M, Cillara N, Restivo A, Deidda S, Spinelli A, Romano C, Bianco F, Sarzo G, Morpurgo E, Belluco C, Palazzari E, Chiloiro G, Meldolesi E, Coco C, Pafundi DP, Feleppa C, Aschele C, Bonomo M, Muratore A, Mellano A, Chiaulon G, Crimì F, Maretto I, Perin A, Urso ED, Scarpa M, Bigon M, Scognamiglio F, Bergamo F, Del Bianco P, Gambacorta MA, Rega D, Pucciarelli S. Rectal Sparing Approach after preoperative Radio- and/or Chemo-therapy (ReSARCh): a prospective, multicenter, observational study. Int J Surg 2024; 110:4736-4745. [PMID: 38518084 PMCID: PMC11326028 DOI: 10.1097/js9.0000000000001322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 03/03/2024] [Indexed: 03/24/2024]
Abstract
BACKGROUND Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years. RESULTS Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9-85.8), 97.6% (95% CI 93.6-99.1), 90.0% (95% CI 84.3-93.7), 94.7% (95% CI 90.1-97.2), and 94.6% (95% CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9-81.2). CONCLUSIONS In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes.
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Affiliation(s)
- Gaya Spolverato
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Quoc Riccardo Bao
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Paolo Delrio
- Department of Colorectal Surgical Oncology, Istituto Nazionale Tumori – IRCCS Fondazione G. Pascale, Naples
| | | | | | | | - Angelo Restivo
- Department of Surgical Science, University of Cagliari, Cagliari
| | - Simona Deidda
- Department of Surgical Science, University of Cagliari, Cagliari
| | - Antonino Spinelli
- Humanitas Clinical and Research Centre, Division of Colon and Rectal Surgery, Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Carmela Romano
- Department of Colorectal Surgical Oncology, Istituto Nazionale Tumori – IRCCS Fondazione G. Pascale, Naples
| | - Francesco Bianco
- Department of Abdominal Oncology, Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale
| | | | - Emilio Morpurgo
- Department of Surgery, Hospital of Camposampiero, Camposampiero
| | - Claudio Belluco
- Department of Surgical Oncology, CRO Aviano National Cancer Institute IRCCS
| | - Elisa Palazzari
- Department of Radiation Oncology, CRO Aviano National Cancer Institute IRCCS, Aviano
| | - Giuditta Chiloiro
- Department of Radiation Oncology, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Elisa Meldolesi
- Department of Radiation Oncology, Fondazione Policlinico Universitario A. Gemelli, IRCCS
| | - Claudio Coco
- Division of General Surgery 2, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma
| | - Donato P. Pafundi
- Division of General Surgery 2, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma
| | | | - Carlo Aschele
- Medical Oncology Unit, Department of Oncology, Ospedale Sant’Andrea, La Spezia
| | | | - Andrea Muratore
- Department of General Surgery, E. Agnelli Hospital, Pinerolo
| | - Alfredo Mellano
- Surgical Oncology Unit, Candiolo Cancer Institute-IRCCS, Turin
| | - Germana Chiaulon
- Department of Radiation Oncology, Azienda Sanitaria Universitaria Integrata, Udine
| | - Filippo Crimì
- Department of Radiology, Department of Medicine (DiMED), University of Padova
| | - Isacco Maretto
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Alessandro Perin
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Emanuele D.L. Urso
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Marco Scarpa
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Mariasole Bigon
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | - Federico Scognamiglio
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
| | | | - Paola Del Bianco
- Clinical Research Unit, Istituto Oncologico Veneto IOV – IRCCS, Padova
| | | | - Daniela Rega
- Department of Colorectal Surgical Oncology, Istituto Nazionale Tumori – IRCCS Fondazione G. Pascale, Naples
| | - Salvatore Pucciarelli
- General Surgery 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova
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Emile SH, Wignakumar A. Non-operative management of rectal cancer: Highlighting the controversies. World J Gastrointest Surg 2024; 16:1501-1506. [PMID: 38983314 PMCID: PMC11230012 DOI: 10.4240/wjgs.v16.i6.1501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/18/2024] [Accepted: 04/23/2024] [Indexed: 06/27/2024] Open
Abstract
There remains much ambiguity on what non-operative management (NOM) of rectal cancer truly entails in terms of the methods to be adopted and the best algorithm to follow. This is clearly shown by the discordance between various national and international guidelines on NOM of rectal cancer. The main aim of the NOM strategy is organ preservation and avoiding unnecessary surgical intervention, which carries its own risk of morbidity. A highly specific and sensitive surveillance program must be devised to avoid patients undergoing unnecessary surgical interventions. In many studies, NOM, often interchangeably called the Watch and Wait strategy, has been shown as a promising treatment option when undertaken in the appropriate patient population, where a clinical complete response is achieved. However, there are no clear guidelines on patient selection for NOM along with the optimal method of surveillance.
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Affiliation(s)
- Sameh Hany Emile
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Anjelli Wignakumar
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
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9
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Wang C, Liu X, Wang W, Miao Z, Li X, Liu D, Hu K. Treatment Options for Distal Rectal Cancer in the Era of Organ Preservation. Curr Treat Options Oncol 2024; 25:434-452. [PMID: 38517596 PMCID: PMC10997725 DOI: 10.1007/s11864-024-01194-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 03/24/2024]
Abstract
OPINION STATEMENT The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.
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Affiliation(s)
- Chen Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Xiaoliang Liu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Weiping Wang
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Zheng Miao
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Xiaoyan Li
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Dingchao Liu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China
| | - Ke Hu
- Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, NO.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, China.
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10
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Obonyo D, Uslar V, Weyhe D, Tabriz N. Personalized medicine for locally advanced rectal cancer: five years of complete clinical response after neoadjuvant radiochemotherapy-a case report with a literature review. Front Surg 2024; 11:1385378. [PMID: 38590724 PMCID: PMC10999613 DOI: 10.3389/fsurg.2024.1385378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 03/11/2024] [Indexed: 04/10/2024] Open
Abstract
We present a case report of a 73-year-old male patient with a complete clinical response following neoadjuvant radiochemotherapy of mid-rectal adenocarcinoma. The patient was initially diagnosed with stage IIIB microsatellite stable mid-rectal adenocarcinoma in February 2017. During restaging in June 2017, which included rectoscopy, endosonography, computed tomography and magnetic resonance imaging, a complete clinical response was observed. After appropriate consultation, a watch-and-wait strategy was chosen. During stringent follow-up every 3 months for the first 3 years and thereafter every 6 months, no recurrence or regrowth was observed. After the fifth year of complete clinical response, we recommended an annual follow-up. As of November 2023, the patient has no signs of recurrence or late toxicity after radiochemotherapy. The omission of resection in patients with locally advanced rectal cancer and the establishment of a watch-and-wait strategy are currently under discussion as possible treatment courses in patients with complete clinical response. Long-term data on watch-and-wait strategies for patients with a complete clinical response in locally advanced rectal cancer are rare. A clear national and international accepted standardization of follow-up programs for patients managed by a watch-and-wait strategy in the long-term is missing. Here, we report the case of a patient who had undergone a follow-up program for more than five years and discuss the current literature. Our case report and literature review highlights that a watch-and-wait strategy does not seem to increase the risk of systemic disease or compromise survival outcomes in selected locally advanced rectal cancer patients. Thus, our case contributes to the growing body of knowledge on personalized and precision medicine for rectal cancer.
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Affiliation(s)
- Dennis Obonyo
- Carl von Ossietzky University Oldenburg, University Clinic for Visceral Surgery, Pius-Hospital Oldenburg, Oldenburg, Germany
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11
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Yang Z, Gao J, Zheng J, Han J, Li A, Liu G, Sun Y, Zhang J, Chen G, Xu R, Zhang X, Liu Y, Bai Z, Deng W, He W, Yao H, Zhang Z. Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study. Signal Transduct Target Ther 2024; 9:56. [PMID: 38462629 PMCID: PMC10925604 DOI: 10.1038/s41392-024-01762-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 01/23/2024] [Accepted: 01/29/2024] [Indexed: 03/12/2024] Open
Abstract
Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850-1000 mg/m2, bid, po, day1-14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6-12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61-53.82%], while 15 (30.0%, 95% CI: 19.1-43.75%), 9 (18.0%, 95% CI: 9.77-30.8%), 2 (4.0%, 95% CI: 1.10-13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.
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Affiliation(s)
- Zhengyang Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jiale Gao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jianyong Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Air Force Medical University, Xi'an, China
| | - Jiagang Han
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ang Li
- Department of General Surgery, Beijing Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Gang Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi Sun
- Department of Anorectal, Tianjin People's Hospital, Tianjin, China
| | - Jie Zhang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guangyong Chen
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Rui Xu
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yishan Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Zhigang Bai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Wei Deng
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Wei He
- Department of Thoracic Surgery / Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
| | - Hongwei Yao
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China.
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China.
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Williams H, Thompson HM, Lin ST, Verheij FS, Omer DM, Qin LX, Garcia-Aguilar J. Endoscopic Predictors of Residual Tumor After Total Neoadjuvant Therapy: A Post Hoc Analysis From the Organ Preservation in Rectal Adenocarcinoma Trial. Dis Colon Rectum 2024; 67:369-376. [PMID: 38039292 PMCID: PMC10922113 DOI: 10.1097/dcr.0000000000003096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2023]
Abstract
BACKGROUND Restaging endoscopy plays a critical role in selecting patients with locally advanced rectal cancer who respond to neoadjuvant therapy for nonoperative management. OBJECTIVE This study evaluated the restaging endoscopic features that best predict the presence of residual tumor in the bowel wall. DESIGN This was a post hoc analysis of a prospective randomized trial. SETTINGS The Organ Preservation in Rectal Adenocarcinoma Trial randomly assigned patients across 18 institutions with stage II/III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Surgeons completed a restaging tumor assessment form, which stratified patients across 3 tiers of clinical response. PATIENTS Patients enrolled in the Organ Preservation in Rectal Adenocarcinoma Trial with a completed tumor assessment form were included. MAIN OUTCOME MEASURES The main outcome was residual tumor, which was defined as either an incomplete clinical response or local tumor regrowth within 2 years of restaging. Independent predictors of residual tumor were identified using backward-selected multivariable logistic regression analysis. Subgroup analyses for complete and near complete clinical responders were performed. RESULTS Surgeons completed restaging forms for 263 patients at a median of 7.7 weeks after neoadjuvant therapy; 128 patients (48.7%) had a residual tumor. On multivariable regression analysis, several characteristics of a near complete response, including ulcer (OR 6.66; 95% CI, 2.54-19.9), irregular mucosa (OR 3.66; 95% CI, 1.61-8.68), and nodularity (OR 2.96; 95% CI, 1.36-6.58), remained independent predictors of residual tumor. A flat scar was associated with lower odds of harboring residual disease (OR 0.32; 95% CI, 0.11-0.93) for patients categorized as clinical complete responders. LIMITATIONS Limitations include analysis of endoscopic features at a single time point and ambiguities in tumor assessment form response criteria. CONCLUSIONS Patients with ulcer, nodularity, or irregular mucosa, on restaging endoscopy have higher odds of residual tumor. Recognizing negative prognostic implications of these features will help surgeons better select candidates for nonoperative management and suggests that patients with high-risk characteristics would benefit from close interval surveillance. See Video Abstract . PREDICTORES ENDOSCPICOS DE TUMOR RESIDUAL DESPUS DE TERAPIA NEOADYUVANTE TOTAL UN ANLISIS POST HOC DEL ENSAYO DE PRESERVACIN DE RGANOS EN ADENOCARCINOMA RECTAL ANTECEDENTES:La reestadificación por endoscopia juega un papel crítico en la selección de pacientes con cáncer de recto localmente avanzado que responden a la terapia neoadyuvante para el manejo no quirúrgico.OBJETIVO:Este estudio evaluó las características endoscópicas de reestadificación que mejor predicen la presencia de tumor residual en la pared intestinal.DISEÑO:Este fue un análisis post hoc de un ensayo prospectivo aleatorizado.ESCENARIO:El ensayo Organ Preservation in Rectal Adenocarcinoma aleatorizó a pacientes de 18 instituciones con adenocarcinoma de recto en estadio II/III para recibir terapia neoadyuvante total de inducción o consolidación. Los cirujanos completaron un formulario de reestadificación de evaluación del tumor, que estratificó a los pacientes en tres niveles de respuesta clínica.PACIENTES:Se incluyeron pacientes inscritos en el ensayo de preservación de órganos en adenocarcinoma rectal con un formulario de evaluación del tumor completado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue presencia de tumor residual, que se definió como una respuesta clínica incompleta o un nuevo crecimiento local del tumor dentro de los dos años posteriores a la reestadificación. Los predictores independientes de tumor residual se identificaron mediante un análisis de regresión logística multivariable seleccionado hacia atrás. Se realizaron análisis de subgrupos para pacientes con respuesta clínica completa y casi completa.RESULTADOS:Los cirujanos completaron formularios de reestadificación para 263 pacientes en una mediana de 7.7 semanas después de la terapia neoadyuvante; 128 (48.7%) tenían tumor residual. En el análisis de regresión multivariable, varias características de una respuesta casi completa, incluyendo úlcera (OR 6.66; IC 95% 2.54-19.9), mucosa irregular (OR 3.66; IC 95% 1.61-8.68) y nodularidad (OR 2.96; IC 95% 1.36 -6.58) siguieron siendo predictores independientes de tumor residual. Una cicatriz plana se asoció con menores probabilidades de albergar enfermedad residual (OR 0.32; IC del 95 %: 0.11-0.93) para los pacientes clasificados como respondedores clínicos completos.LIMITACIONES:Las limitaciones de este estudio incluyen el análisis de las características endoscópicas en un solo momento y las ambigüedades en los criterios de respuesta.en la forma de evaluación del tumorCONCLUSIONES:Los pacientes con úlcera, nodularidad o mucosa irregular en la endoscopia de reestadificación tienen mayores probabilidades de tumor residual. El reconocer las implicaciones pronósticas negativas de estas características ayudará a los cirujanos a seleccionar mejor a los candidatos para el tratamiento no quirúrgico y sugiere que los pacientes con características de alto riesgo se beneficiarían de una vigilancia a intervalos estrechos. (Traducción-Dr. Jorge Silva Velazco ).
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Affiliation(s)
- Hannah Williams
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Hannah M. Thompson
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sabrina T. Lin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Floris S. Verheij
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Dana M. Omer
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Li-Xuan Qin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Julio Garcia-Aguilar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
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Du R, Chang Y, Zhang J, Cheng Y, Li Y, Zhang C, Zhang J, Xu L, Liu Y. Whether the watch-and-wait strategy has application value for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy? A network meta-analysis. Asian J Surg 2024; 47:853-863. [PMID: 38042663 DOI: 10.1016/j.asjsur.2023.11.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/29/2023] [Accepted: 11/10/2023] [Indexed: 12/04/2023] Open
Abstract
The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06-0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10-2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53-3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28-6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years.
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Affiliation(s)
- Rui Du
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Yue Chang
- Cancer Comprehensive Treatment Center, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230000, China
| | - Juan Zhang
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Yuanguang Cheng
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Yonghai Li
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Chengyue Zhang
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Jinyuan Zhang
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Liejuan Xu
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China
| | - Yuancheng Liu
- Department of Anorectal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, 230000, China.
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Klimkowski R, Krzyzkowiak J, Pilonis ND, Bujko K, Kaminski MF. Endoscopic resection of residual rectal neoplasia after definitive chemoradiotherapy for rectal cancer. Best Pract Res Clin Gastroenterol 2024; 68:101896. [PMID: 38522889 DOI: 10.1016/j.bpg.2024.101896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 03/26/2024]
Abstract
The conventional approach to treating locally advanced rectal cancer, commonly defined as cT3 or cT4 primary tumors or with nodal metastases, involves chemoradiation (CRT) followed by surgical resection. There is a growing recognition of the potential for nonsurgical management following CRT or total neoadjuvant therapy (TNT), which allows for organ preservation. "Watch and wait" strategy may be considered if complete clinical response is achieved. In cases when adenoma or superficial cancer is present, a novel approach known as "salvage endoscopic resection of the residual disease" is emerging as a viable nonsurgical option for carefully selected patients. This review discusses available evidence and future potential for endoscopic management of residual neoplasia after oncological treatment of rectal cancer.
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Affiliation(s)
- Robert Klimkowski
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland.
| | - Jakub Krzyzkowiak
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Nastazja Dagny Pilonis
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway; Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland
| | - Krzysztof Bujko
- Department of Radiotherapy I, National Research Institute of Oncology, Warsaw, Poland
| | - Michal F Kaminski
- Department of Gastroenterological Oncology, M. Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Gastroenterology, Hepatology and Oncology, Medical Center for Postgraduate Education, Warsaw, Poland; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway; Department of Surgical Oncology Medical University of Gdansk, Gdansk, Poland
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15
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Marjasuo S, Koskenvuo L, Lepistö A. Findings in magnetic resonance imaging for restaging locally advanced rectal cancer. Int J Colorectal Dis 2024; 39:23. [PMID: 38289485 PMCID: PMC10827956 DOI: 10.1007/s00384-024-04595-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/23/2024] [Indexed: 02/01/2024]
Abstract
PURPOSE We aimed to assess the prognostic value of restaging magnetic resonance imaging (MRI) in rectal cancer after neoadjuvant therapy and compare long-course chemoradiotherapy (LC-CRT) to short-course radiotherapy with delayed surgery (SCRT-delay). METHODS This retrospective study included 267 patients with locally advanced rectal cancer (LARC) operated on between January 2016 and April 2019, all of whom received either LC-CRT or SCRT-delay in the neoadjuvant setting. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS) based on radiological response assessed using the magnetic resonance tumor regression grade (mrTRG). RESULTS In the LC-CRT group, cumulative 1-, 3-, and 5-year OS rates were 94.8%, 86.4%, and 79.0%, while in the SCRT-delay group, they were 83.3%, 68.9%, and 68.9% (P = 0.017). For CSS in the LC-CRT group, cumulative rates were 96.9%, 90.3%, and 85.0%, and in the SCRT-delay group, they were 88.6%, 81.4%, and 81.4% (P = 0.222). There were no significant differences in total histological response rates or local recurrence rates between the treatment groups. The good and moderate response group (mrTRG 1-3) had significantly better cumulative 1-, 3-, and 5-year OS and CSS compared to the poorer response group (mrTRG 4-5) (P = 0.023 for OS and P = 0.048 for CSS). CONCLUSION Unfavorable MRI response is a sign of poor prognosis in LARC. SCRT-delay is comparable to LC-CRT concerning the oncological outcome.
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Affiliation(s)
- Suvi Marjasuo
- Radiology, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
- Tays Central Hospital, Imaging Services, PL 2000, 33521, Tampere, Finland.
| | - Laura Koskenvuo
- Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
| | - Anna Lepistö
- Department of Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Applied Tumor Genomics, Research Programs Unit Organization, University of Helsinki, Helsinki, Finland
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16
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Thompson HM, Omer DM, Lin S, Kim JK, Yuval JB, Veheij FS, Qin LX, Gollub MJ, Wu AJC, Lee M, Patil S, Hezel AF, Marcet JE, Cataldo PA, Polite BN, Herzig DO, Liska D, Oommen S, Friel CM, Ternent CA, Coveler AL, Hunt SR, Garcia-Aguilar J. Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial. JAMA Netw Open 2024; 7:e2350903. [PMID: 38194231 PMCID: PMC10777257 DOI: 10.1001/jamanetworkopen.2023.50903] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/20/2023] [Indexed: 01/10/2024] Open
Abstract
Importance Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration ClinicalTrials.gov Identifier: NCT02008656.
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Affiliation(s)
- Hannah M. Thompson
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Dana M. Omer
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sabrina Lin
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jin K. Kim
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jonathan B. Yuval
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Floris S. Veheij
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Li-Xuan Qin
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marc J. Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Abraham Jing-Ching Wu
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Meghan Lee
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sujata Patil
- Department of Quantitative Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Aram F. Hezel
- James P. Wilmot Cancer Center, University of Rochester, Rochester, New York
| | | | | | - Blase N. Polite
- Department of Surgery, University of Chicago, Chicago, Illinois
| | - Daniel O. Herzig
- Department of Surgery, Oregon Health & Science University, Portland
| | - David Liska
- Department of Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Samuel Oommen
- Department of Surgery, John Muir Health, Walnut Creek, California
| | - Charles M. Friel
- Department of Surgery, University Hospital, University of Virginia Health System, Charlottesville
| | - Charles A. Ternent
- Department of Surgery, Creighton University Medical Center, Omaha, Nebraska
| | | | - Steven R. Hunt
- Department of Surgery, Washington University, St Louis, Missouri
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Lin W, Wee IJY, Seow-En I, Chok AY, Tan EKW. Survival outcomes of salvage surgery in the watch-and-wait approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Ann Coloproctol 2023; 39:447-456. [PMID: 38185947 PMCID: PMC10781598 DOI: 10.3393/ac.2022.01221.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/07/2023] [Accepted: 02/27/2023] [Indexed: 01/09/2024] Open
Abstract
PURPOSE This systematic review and meta-analysis compared the outcomes of the watch-and-wait (WW) approach versus radical surgery (RS) in rectal cancers with clinical complete response (cCR) after neoadjuvant chemoradiotherapy. METHODS This study followed the PRISMA guidelines. Major databases were searched to identify relevant articles. WW and RS were compared through meta-analyses of pooled proportions. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis rates. Pooled salvage surgery rates and outcomes were also collected. The Newcastle-Ottawa scale was employed to assess the risk of bias. RESULTS Eleven studies including 1,112 rectal cancer patients showing cCR after neoadjuvant chemoradiation were included. Of these patients, 378 were treated nonoperatively with WW, 663 underwent RS, and 71 underwent local excision. The 2-year OS (risk ratio [RR], 0.95; P = 0.94), 5-year OS (RR, 2.59; P = 0.25), and distant metastasis rates (RR, 1.05; P = 0.80) showed no significant differences between WW and RS. Local recurrence was more frequent in the WW group (RR, 6.93; P < 0.001), and 78.4% of patients later underwent salvage surgery (R0 resection rate, 97.5%). The 2-year DFS (RR, 1.58; P = 0.05) and 5-year DFS (RR, 2.07; P = 0.02) were higher among RS cases. However, after adjustment for R0 salvage surgery, DFS showed no significant between-group difference (RR, 0.82; P = 0.41). CONCLUSION Local recurrence rates are higher for WW than RS, but complete salvage surgery is often possible with similar long-term outcomes. WW is a viable strategy for rectal cancer with cCR after neoadjuvant chemoradiation, but further research is required to improve patient selection.
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Affiliation(s)
- Wenjie Lin
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Ian Jun Yan Wee
- Department of General Surgery, Singapore General Hospital, Singapore
| | - Isaac Seow-En
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Aik Yong Chok
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
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18
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Sun Myint A, Rao C, Barbet N, Thamphya B, Pace-Loscos T, Schiappa R, Magné N, Martel-Lafay I, Mineur L, Deberne M, Zilli T, Dhadda A, Gerard JP. The safety and efficacy of total mesorectal excision (TME) surgery following dose-escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (OPERA) trial, a European multicentre phase 3 randomised trial (NCT02505750). Colorectal Dis 2023; 25:2160-2169. [PMID: 37837240 DOI: 10.1111/codi.16773] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 08/28/2023] [Accepted: 08/29/2023] [Indexed: 10/15/2023]
Abstract
AIM Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months. METHODS OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2 ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively. RESULTS Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost. CONCLUSION Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.
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Affiliation(s)
| | - Christopher Rao
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Colorectal Surgery, The Cumberland Infirmary, Carlisle, UK
| | | | - Brice Thamphya
- Departement of Epidemiology, Biostatistic, and Health Data, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France
| | - Tanguy Pace-Loscos
- Departement of Epidemiology, Biostatistic, and Health Data, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France
| | - Renaud Schiappa
- Departement of Epidemiology, Biostatistic, and Health Data, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France
| | - Nicolas Magné
- Department of Radiation Oncology, Saint-Priest-en-Jarez, France
| | | | - Laurent Mineur
- Department of Radiation Oncology, Institute Sainte Catherine, Avignon, France
| | | | - Thomas Zilli
- Department of Oncology, University of Genève, Genève, Switzerland
| | | | - Jean Pierre Gerard
- Departement of Epidemiology, Biostatistic, and Health Data, Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France
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19
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Gao Y, Wu A. Organ Preservation in MSS Rectal Cancer. Clin Colon Rectal Surg 2023; 36:430-440. [PMID: 37795468 PMCID: PMC10547535 DOI: 10.1055/s-0043-1767710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2023]
Abstract
Rectal cancer is a heterogeneous disease with complex genetic and molecular subtypes. Emerging progress of neoadjuvant therapy has led to increased pathological and clinical complete response (cCR) rates for microsatellite stable (MSS) rectal cancer, which responds poorly to immune checkpoint inhibitor alone. As a result, organ preservation of MSS rectal cancer as an alternative to radical surgery has gradually become a feasible option. For patients with cCR or near-cCR after neoadjuvant treatment, organ preservation can be implemented safely with less morbidity. Patient selection can be done either before the neoadjuvant treatment for higher probability or after with careful assessment for a favorable outcome. Those patients who achieved a good clinical response are managed with nonoperative management, organ preservation surgery, or radiation therapy alone followed by strict surveillance. The oncological outcomes of patients with careful selection and organ preservation seem to be noninferior compared with those of radical surgery, with lower postoperative morbidity. However, more studies should be done to seek better regression of tumor and maximize the possibility of organ preservation in MSS rectal cancer.
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Affiliation(s)
- Yuye Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Aiwen Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
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20
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Xiao B, Yu J, Ding PR. Nonoperative Management of dMMR/MSI-H Colorectal Cancer following Neoadjuvant Immunotherapy: A Narrative Review. Clin Colon Rectal Surg 2023; 36:378-384. [PMID: 37795463 PMCID: PMC10547541 DOI: 10.1055/s-0043-1767703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/06/2023]
Abstract
Immunotherapy with PD-1 blockade has achieved a great success in colorectal cancers (CRCs) with high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR), and has become the first-line therapy in metastatic setting. Studies of neoadjuvant immunotherapy also report exciting results, showing high rates of clinical complete response (cCR) and pathological complete response. The high efficacy and long duration of response of immunotherapy has prompt attempts to adopt watch-and-wait strategy for patients achieving cCR following the treatment. Thankfully, the watch-and-wait approach has been proposed for nearly 20 years for patients undergoing chemoradiotherapy and has gained ground among patients as well as clinicians. In this narrative review, we combed through the available information on immunotherapy for CRC and on the watch-and-wait strategy in chemoradiotherapy, and looked forward to a future where neoadjuvant immunotherapy as a curative therapy would play a big part in the treatment of MSI-H/dMMR CRC.
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Affiliation(s)
- Binyi Xiao
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China
| | - Jiehai Yu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China
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21
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Tan S, Gao Q, Cui Y, Ou Y, Huang S, Feng W. Oncologic outcomes of watch-and-wait strategy or surgery for low to intermediate rectal cancer in clinical complete remission after adjuvant chemotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 2023; 38:246. [PMID: 37787779 DOI: 10.1007/s00384-023-04534-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/18/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial. OBJECTIVE The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies. METHODS Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission. RESULTS In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group. CONCLUSION There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.
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Affiliation(s)
- Shufa Tan
- Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Qiangqiang Gao
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Deputy No. 2, West Weiyang Road, Xianyang City, Shaanxi Province, 712000, China
| | - Yaping Cui
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Deputy No. 2, West Weiyang Road, Xianyang City, Shaanxi Province, 712000, China
| | - Yan Ou
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Deputy No. 2, West Weiyang Road, Xianyang City, Shaanxi Province, 712000, China
| | - Shuilan Huang
- Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Wenzhe Feng
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Deputy No. 2, West Weiyang Road, Xianyang City, Shaanxi Province, 712000, China.
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22
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Quezada-Diaz FF, Smith JJ. Is Nonoperative Management of Rectal Cancer Feasible? Adv Surg 2023; 57:141-154. [PMID: 37536849 PMCID: PMC10926904 DOI: 10.1016/j.yasu.2023.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
During the past decade, the treatment of locally advanced rectal cancer (LARC) has become more complex. Total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathologic complete response, resulting in improved long-term oncological outcomes. The feasibility to implement nonoperative management (NOM) depends on solving current challenges such as how to correctly identify the best candidates for a NOM without compromising oncologic safety. NOM should be part of the treatment discussion of LARC, considering increasing rates of clinical complete response, potential quality of life gains, avoidance of surgical morbidity, and patient preferences.
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Affiliation(s)
- Felipe F Quezada-Diaz
- Colorectal Unit, Department of Surgery, Complejo Asistencial Doctor Sótero del Río, Santiago, Región Metropolitana, Chile. https://twitter.com/ffquezad
| | - Jesse Joshua Smith
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue | SR-201, New York, NY 10065, USA.
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23
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Kalady MF, Steele SR. Top Colorectal Articles from 2021 to Inform Your Cancer Practice. Ann Surg Oncol 2023; 30:5489-5494. [PMID: 37285092 DOI: 10.1245/s10434-023-13651-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 05/03/2023] [Indexed: 06/08/2023]
Abstract
Multimodality treatment for locally advanced rectal cancer is the standard of care. Treatments include surgery, radiation, and chemotherapy, with medical therapies now being favored in the neoadjuvant setting. Various regimens continue to be studied and defined in prospective randomized trials. The PRODIGE 23 and RAPIDO trials showed improved disease-free survival and pathologic complete response rates for split chemotherapy/radiation treatment and short-course radiation with consolidation chemotherapy, respectively; both compared with traditional neoadjuvant long course chemoradiation, surgery, and adjuvant chemotherapy. Furthermore, new regimens are yielding a higher rate of complete clinical response, allowing for non-operative management. Circulating tumor DNA provides a potential novel option for monitoring response to treatment and rectal cancer surveillance. This manuscript summarizes some of the key clinical trials and studies that are defining clinical practice.
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Affiliation(s)
- Matthew F Kalady
- Division of Colon and Rectal Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
| | - Scott R Steele
- Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
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24
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Yuval JB, Patil S, Gangai N, Omer DM, Akselrod DG, Fung A, Harmath CB, Kampalath R, Krehbiel K, Lee S, Liu PS, Millet JD, O'Malley RB, Purysko AS, Veniero JC, Wasnik AP, Garcia-Aguilar J, Gollub MJ. MRI assessment of rectal cancer response to neoadjuvant therapy: a multireader study. Eur Radiol 2023; 33:5761-5768. [PMID: 36814032 PMCID: PMC10394731 DOI: 10.1007/s00330-023-09480-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 12/05/2022] [Accepted: 01/27/2023] [Indexed: 02/24/2023]
Abstract
OBJECTIVES A watch and wait strategy with the goal of organ preservation is an emerging treatment paradigm for rectal cancer following neoadjuvant treatment. However, the selection of appropriate patients remains a challenge. Most previous efforts to measure the accuracy of MRI in assessing rectal cancer response used a small number of radiologists and did not report variability among them. METHODS Twelve radiologists from 8 institutions assessed baseline and restaging MRI scans of 39 patients. The participating radiologists were asked to assess MRI features and to categorize the overall response as complete or incomplete. The reference standard was pathological complete response or a sustained clinical response for > 2 years. RESULTS We measured the accuracy and described the interobserver variability of interpretation of rectal cancer response between radiologists at different medical centers. Overall accuracy was 64%, with a sensitivity of 65% for detecting complete response and specificity of 63% for detecting residual tumor. Interpretation of the overall response was more accurate than the interpretation of any individual feature. Variability of interpretation was dependent on the patient and imaging feature investigated. In general, variability and accuracy were inversely correlated. CONCLUSIONS MRI-based evaluation of response at restaging is insufficiently accurate and has substantial variability of interpretation. Although some patients' response to neoadjuvant treatment on MRI may be easily recognizable, as seen by high accuracy and low variability, that is not the case for most patients. KEY POINTS • The overall accuracy of MRI-based response assessment is low and radiologists differed in their interpretation of key imaging features. • Some patients' scans were interpreted with high accuracy and low variability, suggesting that these patients' pattern of response is easier to interpret. • The most accurate assessments were those of the overall response, which took into consideration both T2W and DWI sequences and the assessment of both the primary tumor and the lymph nodes.
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Affiliation(s)
- Jonathan B Yuval
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, USA
- Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Sujata Patil
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, USA
| | - Natalie Gangai
- Department of Radiology, Memorial Sloan Kettering Cancer Center, NY, USA
| | - Dana M Omer
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, USA
| | | | - Alice Fung
- Department of Radiology, Oregon Health & Sciences University, Portland, USA
| | - Carla B Harmath
- Department of Radiology, University of Chicago, Chicago, USA
| | - Rony Kampalath
- Department of Radiology, University of California Irvine, Irvine, USA
| | - Kyle Krehbiel
- Department of Radiology, Creighton University Medical Center - Bergan Mercy, Omaha, USA
| | - Sonia Lee
- Department of Radiology, University of California Irvine, Irvine, USA
| | - Peter S Liu
- Department of Radiology, Cleveland Clinic, Cleveland, USA
| | - John D Millet
- Department of Radiology, University of Michigan, Ann Arbor, USA
| | - Ryan B O'Malley
- Department of Radiology, University of Washington, Seattle, USA
| | | | | | - Ashish P Wasnik
- Department of Radiology, University of Michigan, Ann Arbor, USA
| | - Julio Garcia-Aguilar
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, USA
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, NY, USA.
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25
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Georges C, Yap R, Bell S, Farmer KC, Cohen LCL, Wilkins S, Centauri S, Engel R, Oliva K, McMurrick PJ. Comparison of quality of life, symptom and functional outcomes following surgical treatment for colorectal neoplasia. ANZ J Surg 2023; 93:1877-1884. [PMID: 37173802 DOI: 10.1111/ans.18510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/04/2023] [Accepted: 04/30/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND Colorectal surgical procedures can have a significant impact on quality-of-life (QoL), functional and symptom outcomes. This retrospective study conducted in a tertiary care center evaluated the influence of four colorectal surgical procedures on patient-reported outcome measures (PROMs). METHODS 512 patients undergoing colorectal neoplasia surgery between June 2015 and December 2017 were identified via the Cabrini Monash Colorectal Neoplasia database. Primary outcomes measured were the mean changes in PROMs following surgery utilizing the International Consortium of Health Outcome Measures colorectal cancer (CRC) PROMs. RESULTS 242 patients from 483 eligible patients responded (50% participation rate). Responders and non-responders were comparable in median age (72 vs. 70 years), gender (48% vs. 52% male), time from surgery (<1 and >1 year), overall stage at diagnosis and type of surgery. Respondents underwent either a right hemicolectomy, ultra-low anterior resection, abdominoperineal resection or a transanal endoscopic microsurgery/transanal minimally invasive surgery. Right hemicolectomy patients reported the best post-operative function and reduced symptoms, significantly better (P < 0.01) than ultra-low anterior resection patients who reported the worst outcomes in multiple areas (body image, embarrassment, flatulence, diarrhoea, stool frequency). Furthermore, patients undergoing an abdominoperineal resection reported the worst scores for body image, urinary frequency, urinary incontinence, buttock pain, faecal incontinence and male impotence. CONCLUSIONS The differences in PROMs in CRC surgical procedures is demonstrable. The worst post-operative functional and symptom scores were reported after either an ultra-low anterior resection or an abdominoperineal resection. Implementation of PROMs will identify and aid early patient referral to allied health and support services.
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Affiliation(s)
- Christine Georges
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Medicine, Alfred Hospital, Melbourne, Victoria, Australia
| | - Raymond Yap
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
| | - Stephen Bell
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Colorectal and General Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Keith Chip Farmer
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Colorectal and General Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Lauren C L Cohen
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
| | - Simon Wilkins
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Suellyn Centauri
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
| | - Rebekah Engel
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
- Stem Cells and Development Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Karen Oliva
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
- Department of Colorectal and General Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Paul J McMurrick
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia
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Couwenberg AM, Varvoglis DN, Grieb BC, Marijnen CA, Ciombor KK, Guillem JG. New Opportunities for Minimizing Toxicity in Rectal Cancer Management. Am Soc Clin Oncol Educ Book 2023; 43:e389558. [PMID: 37307515 PMCID: PMC10450577 DOI: 10.1200/edbk_389558] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Advances in multimodal management of locally advanced rectal cancer (LARC), consisting of preoperative chemotherapy and/or radiotherapy followed by surgery with or without adjuvant chemotherapy, have improved local disease control and patient survival but are associated with significant risk for acute and long-term morbidity. Recently published trials, evaluating treatment dose intensification via the addition of preoperative induction or consolidation chemotherapy (total neoadjuvant therapy [TNT]), have demonstrated improved tumor response rates while maintaining acceptable toxicity. In addition, TNT has led to an increased number of patients achieving a clinical complete response and thus eligible to pursue a nonoperative, organ-preserving, watch and wait approach, thereby avoiding toxicities associated with surgery, such as bowel dysfunction and stoma-related complications. Ongoing trials using immune checkpoint inhibitors in patients with mismatch repair-deficient tumors suggest that this subgroup of patients with LARC could potentially be treated with immunotherapy alone, sparing them the toxicity associated with preoperative treatment and surgery. However, the majority of rectal cancers are mismatch repair-proficient and less responsive to immune checkpoint inhibitors and require multimodal management. The synergy noted in preclinical studies between immunotherapy and radiotherapy on immunogenic tumor cell death has led to the design of ongoing clinical trials that explore the benefit of combining radiotherapy, chemotherapy, and immunotherapy (mainly of immune checkpoint inhibitors) and aim to increase the number of patients eligible for organ preservation.
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Affiliation(s)
- Alice M. Couwenberg
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Brian C. Grieb
- Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Corrie A.M. Marijnen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands
| | - Kristen K. Ciombor
- Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Jose G. Guillem
- Department of Surgery, Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, NC
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Temmink SJD, Peeters KCMJ, Bahadoer RR, Kranenbarg EMK, Roodvoets AGH, Melenhorst J, Burger JWA, Wolthuis A, Renehan AG, Figueiredo NL, Pares O, Martling A, Perez RO, Beets GL, van de Velde CJH, Nilsson PJ. Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD). Br J Surg 2023; 110:676-684. [PMID: 36972213 PMCID: PMC10364523 DOI: 10.1093/bjs/znad051] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 01/13/2023] [Accepted: 02/05/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. METHODS This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality. RESULTS A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. CONCLUSION Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment.
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Affiliation(s)
- Sofieke J D Temmink
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Koen C M J Peeters
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - Renu R Bahadoer
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | | | - Annet G H Roodvoets
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - Jarno Melenhorst
- Department of Surgery, Maastricht Universitair Medisch Centrum+, Maastricht, the Netherlands
| | | | - Albert Wolthuis
- Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Andrew G Renehan
- Manchester Cancer Research Centre, National Institute for Health Research Manchester Biomedical Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK
- Colorectal and Peritoneal Oncology Centre, Christie National Health Service Foundation Trust, Manchester, UK
| | | | - Oriol Pares
- Department of Radiation Oncology, Champalimaud Foundation, Lisbon, Portugal
| | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Rodrigo O Perez
- Department of Colorectal Surgery, Angelita and Joaquim Gama Institute, São Paulo, Brazil
- Department of Surgical Oncology, Hospital Beneficencia Portuguesa, São Paulo, Brazil
- Colorectal Surgery Division, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
- Ludwig Institute for Cancer Research, São Paulo Branch, São Paulo, Brazil
| | - Geerard L Beets
- Department of Surgery, Netherlands Cancer Institute—Antoni van Leeuwenhoek, Amsterdam, the Netherlands
- GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | | | - Per J Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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Thompson HM, Kim JK, Jimenez-Rodriguez RM, Garcia-Aguilar J, Veeraraghavan H. Deep Learning-Based Model for Identifying Tumors in Endoscopic Images From Patients With Locally Advanced Rectal Cancer Treated With Total Neoadjuvant Therapy. Dis Colon Rectum 2023; 66:383-391. [PMID: 35358109 PMCID: PMC10185333 DOI: 10.1097/dcr.0000000000002295] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND A barrier to the widespread adoption of watch-and-wait management for locally advanced rectal cancer is the inaccuracy and variability of identifying tumor response endoscopically in patients who have completed total neoadjuvant therapy (chemoradiotherapy and systemic chemotherapy). OBJECTIVE This study aimed to develop a novel method of identifying the presence or absence of a tumor in endoscopic images using deep convolutional neural network-based automatic classification and to assess the accuracy of the method. DESIGN In this prospective pilot study, endoscopic images obtained before, during, and after total neoadjuvant therapy were grouped on the basis of tumor presence. A convolutional neural network was modified for probabilistic classification of tumor versus no tumor and trained with an endoscopic image set. After training, a testing endoscopic imaging set was applied to the network. SETTINGS The study was conducted at a comprehensive cancer center. PATIENTS Images were analyzed from 109 patients who were diagnosed with locally advanced rectal cancer between December 2012 and July 2017 and who underwent total neoadjuvant therapy. MAIN OUTCOME MEASURES The main outcomes were accuracy of identifying tumor presence or absence in endoscopic images measured as area under the receiver operating characteristic for the training and testing image sets. RESULTS A total of 1392 images were included; 1099 images (468 of no tumor and 631 of tumor) were for training and 293 images (151 of no tumor and 142 of tumor) for testing. The area under the receiver operating characteristic for training and testing was 0.83. LIMITATIONS The study had a limited number of images in each set and was conducted at a single institution. CONCLUSIONS The convolutional neural network method is moderately accurate in distinguishing tumor from no tumor. Further research should focus on validating the convolutional neural network on a large image set. See Video Abstract at http://links.lww.com/DCR/B959 . MODELO BASADO EN APRENDIZAJE PROFUNDO PARA IDENTIFICAR TUMORES EN IMGENES ENDOSCPICAS DE PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL ANTECEDENTES:Una barrera para la aceptación generalizada del tratamiento de Observar y Esperar para el cáncer de recto localmente avanzado, es la imprecisión y la variabilidad en la identificación de la respuesta tumoral endoscópica, en pacientes que completaron la terapia neoadyuvante total (quimiorradioterapia y quimioterapia sistémica).OBJETIVO:Desarrollar un método novedoso para identificar la presencia o ausencia de un tumor en imágenes endoscópicas utilizando una clasificación automática basada en redes neuronales convolucionales profundas y evaluar la precisión del método.DISEÑO:Las imágenes endoscópicas obtenidas antes, durante y después de la terapia neoadyuvante total se agruparon en base de la presencia del tumor. Se modificó una red neuronal convolucional para la clasificación probabilística de tumor versus no tumor y se entrenó con un conjunto de imágenes endoscópicas. Después del entrenamiento, se aplicó a la red un conjunto de imágenes endoscópicas de prueba.ENTORNO CLINICO:El estudio se realizó en un centro oncológico integral.PACIENTES:Analizamos imágenes de 109 pacientes que fueron diagnosticados de cáncer de recto localmente avanzado entre diciembre de 2012 y julio de 2017 y que se sometieron a terapia neoadyuvante total.PRINCIPALES MEDIDAS DE VALORACION:La precisión en la identificación de la presencia o ausencia de tumores en imágenes endoscópicas medidas como el área bajo la curva de funcionamiento del receptor para los conjuntos de imágenes de entrenamiento y prueba.RESULTADOS:Se incluyeron mil trescientas noventa y dos imágenes: 1099 (468 sin tumor y 631 con tumor) para entrenamiento y 293 (151 sin tumor y 142 con tumor) para prueba. El área bajo la curva operativa del receptor para entrenamiento y prueba fue de 0,83.LIMITACIONES:El estudio tuvo un número limitado de imágenes en cada conjunto y se realizó en una sola institución.CONCLUSIÓN:El método de la red neuronal convolucional es moderadamente preciso para distinguir el tumor de ningún tumor. La investigación adicional debería centrarse en validar la red neuronal convolucional en un conjunto de imágenes mayor. Consulte Video Resumen en http://links.lww.com/DCR/B959 . (Traducción -Dr. Fidel Ruiz Healy ).
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Affiliation(s)
- Hannah M Thompson
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jin K Kim
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Harini Veeraraghavan
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
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Lauretta A, Montori G, Guerrini GP. Surveillance strategies following curative resection and non-operative approach of rectal cancer: How and how long? Review of current recommendations. World J Gastrointest Surg 2023; 15:177-192. [PMID: 36896297 PMCID: PMC9988648 DOI: 10.4240/wjgs.v15.i2.177] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/30/2022] [Accepted: 01/18/2023] [Indexed: 02/27/2023] Open
Abstract
Different follow-up strategies are available for patients with rectal cancer following curative treatment. A combination of biochemical testing and imaging investigation, associated with physical examination are commonly used. However, there is currently no consensus about the types of tests to perform, the timing of the testing, and even the need for follow-up at all has been questioned. The aim of this study was to review the evidence of the impact of different follow-up tests and programs in patients with non-metastatic disease after definitive treatment of the primary. A literature review was performed of studies published on MEDLINE, EMBASE, the Cochrane Library and Web of Science up to November 2022. Current published guidelines from the most authoritative specialty societies were also reviewed. According to the follow-up strategies available, the office visit is not efficient but represents the only way to maintain direct contact with the patient and is recommended by all authoritative specialty societies. In colorectal cancer surveillance, carcinoembryonic antigen represents the only established tumor marker. Abdominal and chest computed tomography scan is recommended considering that the liver and lungs are the most common sites of recurrence. Since local relapse in rectal cancer is higher than in colon cancer, endoscopic surveillance is mandatory. Different follow-up regimens have been published but randomized comparisons and meta-analyses do not allow to determine whether intensive or less intensive follow-up had any significant influence on survival and recurrence detection rate. The available data do not allow the drawing of final conclusions on the ideal surveillance methods and the frequency with which they should be applied. It is very useful and urgent for clinicians to identify a cost-effective strategy that allows early identification of recurrence with a special focus for high-risk patients and patients undergoing a “watch and wait” approach.
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Affiliation(s)
- Andrea Lauretta
- Department of Surgical Oncology, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano 33081, Italy
| | - Giulia Montori
- Department of General Surgery, Vittorio Veneto Hospital, ULSS 2 Marca Trevigiana, Vittorio Veneto 31029, Italy
| | - Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgical Oncology and Liver Transplantation Unit, Policlinico-AUO Modena, Modena 41124, Italy
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Grotenhuis BA, Beets GL. Watch-and-Wait is an Option in Rectal Cancer Patients: From Controversy to Common Clinical Practice. Clin Oncol (R Coll Radiol) 2023; 35:124-129. [PMID: 36481218 DOI: 10.1016/j.clon.2022.11.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 10/26/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Abstract
Overview of the introduction of organ preservation in rectal cancer patients and future challenges.
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Affiliation(s)
- B A Grotenhuis
- Department of Surgical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - G L Beets
- GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
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Dai D, Liu G, Liu H, Liu Y, Liu X, Li S, Lei Y, Gao Y, Wang Y, Zhang S, Zhang R. Clinical feasibility of the therapeutic strategies total neoadjuvant therapy and "watch and wait" in the treatment of rectal cancer patients with recurrence after clinical complete response. Front Surg 2023; 9:1006624. [PMID: 36726944 PMCID: PMC9885041 DOI: 10.3389/fsurg.2022.1006624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 12/28/2022] [Indexed: 01/17/2023] Open
Abstract
Purpose In recent years, total neoadjuvant therapy (TNT) has emerged as a new therapeutic strategy against advanced rectal cancer (RC). After administration of TNT, some patients show complete clinical response (cCR) to treatment however, disputes about the effects of TNT and the alternative treatment plans in case of recurrence after cCR still exist. Methods A total of 100 patients were included in this paper. CR and non-CR was observed when these patients were administered with TNT at the First Affiliated Hospital of Dalian Medical University, China from May 2015 to June 2021. These patients received different chemotherapeutic regimens, with close monitoring and watch and wait (W&W) strategy being applied by a multidisciplinary team (MDT). According to treatment results, patients were divided into a cCR group and a non-cCR group; according to the recurrence during W&W, they were divided into a recurrence group and a no-local-recurrence group. This study analyzed the factors that may affect the prognosis, and summarized the surgery and treatment after recurrence. Results The TNT strategy was effective, and 85% of patients achieved local remission. However, W&W did not affect the survival time of CR patients, nor did it cause new distant metastasis due to local recurrence during the observation period (P > 0.05). However, for patients with positive CRM, we do not recommend W&W as the first choice of treatment (P < 0.05). Conclusion (1) Whole-course neoadjuvant therapy was an effective treatment scheme for advanced mid-term rectal cancer. The total local reduction rate of this group of cases was 85.00%, meaning that 25 patients achieved CR. (2) W&W was safe and reliable, and CR patients could receive it as the preferred treatment. (3) CRM was an independent risk factor for local recurrence in CR patients. We do not recommend W&W as the preferred treatment for CR patients with positive CRM.
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Affiliation(s)
- Dianyin Dai
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ge Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China,Correspondence: Ge Liu
| | - Huanran Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yanfeng Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xinlu Liu
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shuang Li
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yanan Lei
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yun Gao
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yuezhu Wang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shoujia Zhang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ran Zhang
- Department of Anorectal Surgery, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Piercey O, Tie J. Circulating tumour DNA in the evolving treatment landscape of locally advanced rectal cancer: where does it fit in? Ther Adv Med Oncol 2023; 15:17588359231160138. [PMID: 36936200 PMCID: PMC10017954 DOI: 10.1177/17588359231160138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 02/03/2023] [Indexed: 03/16/2023] Open
Abstract
The management of locally advanced rectal cancer (LARC) requires multimodality treatment, typically with neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. However, the treatment landscape is rapidly evolving with total neoadjuvant therapy and non-operative management for selected patients emerging as other novel treatment approaches. With so many treatment options, there is a need for biomarkers to direct a more personalised treatment strategy for patients with LARC. In this review, we summarise the available data regarding the use of circulating tumour DNA (ctDNA) in patients with LARC, as both a marker of treatment response to neoadjuvant therapy and as a marker of minimal residual disease (MRD) after patients have completed definitive local treatment. To date, the ability of ctDNA status to predict for pathologic complete response at any timepoint during multimodality treatment has been variably reported. The most consistent finding across available studies is the ability of ctDNA to detect MRD after CRT and surgery, the presence of which confers a significantly poor prognosis, with increased risk of cancer recurrence and worse overall survival. It is yet to be determined if providing additional therapies to patients with MRD improves outcomes. The available studies assessing the potential utility of ctDNA in LARC are limited by significant heterogeneity in the choice of ctDNA assay, timepoint at which ctDNA was collected, treatment that patients received and length of follow-up, leading to uncertainties about how to implement it into daily clinical practice. As the treatment landscape evolves, larger randomised trials assessing the role of ctDNA in LARC are needed.
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Affiliation(s)
- Oliver Piercey
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
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Lins Neto MÁDF, Salvador Filho LHA, Coelho JAPDM, Rolim JODM. Watch and Wait, Worth It? JOURNAL OF COLOPROCTOLOGY 2022. [DOI: 10.1055/s-0042-1758206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Abstract
Background The surgery with total mesorectal excision recommended by R. J. Heald in 1982 is the gold standard. Rectal cancer (RC) surgery has a morbidity rate ranging from 6 to 35%, and it can cause functional issues such as sexual, urinary, and bowel dysfunction in the long term. Neoadjuvant chemoradiotherapy (CRT) has been gaining ground in patients with lesions in the middle and lower rectum. The aim of the present study is to present the experience of a reference service in the treatment of RC.
Patients and Methods A retrospective study involving 53 patients diagnosed with RC between January 2017 and December 2019 with follow-up until December 2020. We examined tumor location, disease stage, digital rectal exam findings, carcinoembryonic antigen (CEA), therapeutic modality offered, and follow-up time.
Results A total of 32% of the patients were men and 68% were women, with a mean age of 60 years old. Location: upper rectum in 6 cases, middle rectum in 21 cases, and lower rectum in 26 cases with evolution from 9.8 to 13.5 months. The most frequent complaints were hematochezia and constipation. A total of 36 patients underwent neoadjuvant therapy: 11 complete clinical response (CCR) (30.5%), 20 (55.5%) partial clinical response (PCR), and no response in 5 patients (14%). The follow-up ranged from 12 to 48 months, with a mean of 30.5 months. A total of 25% of the patients had RC that went beyond the mesorectal fascia, and 22.64% had metastases in other parts of the body when they were diagnosed.
Conclusion Neoadjuvant radio and chemotherapy present themselves as an alternative in the treatment of rectal cancer. In 36 patients, 30.5% had a complete clinical response, 55.5% had a partial clinical response, and 14% had no response. It was worth doing the “Watch and Wait” (W&W) to sample. A definitive colostomy was avoided. However, it is necessary to expand the study to a larger follow-up and more patients. Additionally, it is necessary to implement a multicenter study.
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Affiliation(s)
| | | | | | - João Otávio de Moraes Rolim
- Coloproctology Service, Hospital Universitário Professor Alberto Antunes, Universidade Federal do Alagoas, Maceió, AL, Brazil
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Koëter T, Jongen G, Hanrath-Vos E, Smit E, Fütterer J, Maas M, Scheenen T. Reducing Acquisition Time of Diffusion Weighted MR Imaging of the Rectum with Simultaneous Multi-Slice Acquisition: A Reader Study. Acad Radiol 2022; 29:1802-1807. [PMID: 35256274 DOI: 10.1016/j.acra.2022.02.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/03/2022] [Accepted: 02/05/2022] [Indexed: 01/26/2023]
Abstract
RATIONALE AND OBJECTIVES To assess the acquisition time and image quality of simultaneous multislice-accelerated diffusion-weighted imaging (SMS-DWI) versus conventional DWI (C-DWI) of the rectum. MATERIALS AND METHODS In patients scheduled for a magnetic resonance imaging of the rectum, both SMS-DWI and C-DWI were performed on a 3T whole body magnetic resonance scanner. Image quality of the DWI sequences was reviewed by two independent radiologists who were blinded to the method of imaging using a five-point Likert scale: (score ranging from 1 (non-diagnostic) to 5 (excellent). The mean scores of SMS-DWI versus C-DWI were compared for the individual readers using a nonparametric test (Wilcoxon signed ranks). RESULTS The SMS-DWI protocol acquisition time was 4:08 min vs. 7:24 min per patient, which led to a reduction of 44.1% for the C-DWI protocol, both excluding time for sequence specific adjustments (shimming). No statistical differences between the conventional-, and SMS- diffusion weighted images were seen for both readers. Mean overall image quality of the SMS-DWI TRACE images was 3.5 (SD: 1.3) and 3.3 (SD: 1.0) for reader 1 and reader 2, respectively. Mean overall image quality of the C-DWI TRACE images was 3.4 (SD: 1.3) and 3.2 (SD: 1.1) for reader 1 and reader 2, respectively. CONCLUSION Optimized SMS-DWI compared to C-DWI in imaging of the rectum showed similar image quality while a significant acquisition time reduction was achieved.
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Affiliation(s)
- Tijmen Koëter
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands; Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands.
| | - Germaine Jongen
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Eline Hanrath-Vos
- Department of Radiology, Elisabeth-TweeSteden Ziekenhuis (ETZ), Tilburg, The Netherlands
| | - Ewoud Smit
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Jurgen Fütterer
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Marnix Maas
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Tom Scheenen
- Department of Medical Imaging, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
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Transanal Endoscopic Microsurgery Versus Total Mesorectal Excision in ypT0-1 Rectal Cancer After Preoperative Radiochemotherapy: Postoperative Morbidity, Functional Results, and Long-term Oncologic Outcome. Dis Colon Rectum 2022; 65:1306-1315. [PMID: 35067503 DOI: 10.1097/dcr.0000000000002255] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND In patients with locally advanced extraperitoneal rectal cancer, a multidisciplinary approach represents the standard treatment. However, considering the favorable prognosis in patients with major or complete response, radical surgery might represent overtreatment. OBJECTIVE This study aimed to evaluate postoperative short-term morbidity, functional outcome, and oncologic long-term outcome in patients with rectal cancer treated with local excision by transanal endoscopic microsurgery or radical surgery and to determine who achieved a complete or major pathological response (ypT0-1) after neoadjuvant treatment. DESIGN This was a retrospective study. SETTING The study was conducted at a single center. PATIENTS Patients who had received neoadjuvant treatment by local excision with a major or complete pathological response at histological examination (transanal endoscopic microsurgery group) were compared to patients treated by radical surgery with the same pathological response (total mesorectal excision group). INTERVENTIONS The interventions included local excision by transanal endoscopic microsurgery and radical surgery with total mesorectal excision. MAIN OUTCOME MEASURES Postoperative short-term morbidity, functional outcome 1 year after surgery, and oncologic long-term outcome were measured. RESULTS Ninety-three patients were included in the study (35 in the transanal endoscopic microsurgery group and 58 in the mesorectal excision group). In the total mesorectal excision group, a sphincter-saving approach was possible in 89.7% (vs 100%; p = 0.049); a protective temporary stoma was necessary in 74.1% of radical procedures (vs 0%; p < 0.001), and 13.8% of these became permanent. Short-term postoperative morbidity was lower after local excision (14.3% vs 46.6%; p = 0.002). One year after surgery, the transanal endoscopic microsurgery group recorded better evacuation and continence function than the total mesorectal excision group. Oncologic outcome was similar between the groups. LIMITATIONS This study had a retrospective design. CONCLUSION If a major or complete pathological response occurs after neoadjuvant treatment, an organ-sparing approach by local excision seems to offer the same oncologic results as radical surgery, but it has a better postoperative morbidity rate and better functional results. See Video Abstract at http://links.lww.com/DCR/B901 .Microcirugía endoscópica transanal versus escisión total del mesorrecto en cáncer de recto ypT0-1 después de radioquimioterapia preoperatoria: morbilidad posoperatoria, resultados funcionales y resultado oncológico a largo plazo. ANTECEDENTES En pacientes con cáncer rectal extraperitoneal localmente avanzado, un abordaje multidisciplinario con radioquimioterapia preoperatoria y cirugía con escisión total del mesorrecto representa el tratamiento estándar. En pacientes que obtienen una respuesta mayor o completa, la cirugía radical puede representar un sobretratamiento, considerando el pronóstico favorable de estos casos. OBJETIVO Evaluar la morbilidad posoperatoria a corto plazo, el resultado funcional y el resultado oncológico a largo plazo en pacientes con cáncer de recto tratados con escisión local mediante microcirugía endoscópica transanal o mediante cirugía radical y que obtuvieron una respuesta patológica completa o mayor (ypT0-1) después del tratamiento neoadyuvante. DISEO Este fue un estudio retrospectivo. AJUSTE El estudio se realizó en un solo centro. ESCENARIO El estudio se realizó en un solo centro. PACIENTES Se comparó a los pacientes tratados, tras tratamiento neoadyuvante (1996-2016), mediante escisión local con respuesta patológica mayor o completa al examen histológico (grupo de microcirugía endoscópica transanal), con los pacientes tratados mediante cirugía radical con la misma respuesta patológica (grupo de escisión mesorrectal total). INTERVENCIONES Extirpación local mediante microcirugía endoscópica transanal y cirugía radical con escisión mesorrectal total. PRINCIPALES MEDIDAS DE RESULTADO Morbilidad posoperatoria a corto plazo, resultado funcional a un año después de la cirugía (evaluado con una puntuación de evacuación y continencia) y resultado oncológico a largo plazo. LIMITACIONES Las limitaciones de este estudio incluyen su diseño retrospectivo. CONCLUSIN Si se produce una respuesta patológica mayor o completa después del tratamiento neoadyuvante, un abordaje con preservación de órganos mediante escisión local parece ofrecer los mismos resultados oncológicos que la cirugía radical, pero tiene una menor tasa de morbilidad postoperatoria y mejores resultados funcionales un año después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/B901 . (Traducción-Dr. Felipe Bellolio ).
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Yang F, Hill J, Abraham A, Ghosh S, Steed T, Kurtz C, Joseph K, Yun J, Warkentin B, Thai J, Nijjar T, Severin D, Tankel K, Fairchild A, Usmani N. Tumor Volume Predicts for Pathologic Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation. Am J Clin Oncol 2022; 45:405-409. [PMID: 36106894 DOI: 10.1097/coc.0000000000000942] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM. MATERIALS AND METHODS In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis. Tumor volumes were derived from pretreatment MRI. Clinical parameters such as tumor volume, stage, and location were analyzed by univariate and multivariate analysis, against pCR. A receiver operator characteristic curve was generated to identify a tumor volume cut-off with the highest clinically relevant Youden index for predicting pCR. RESULTS Seventy-five of 412 patients (18%) achieved pCR. A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR. On regression analysis, a tumor volume >37.3 cm 3 was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV <37.3 cm 3 [odds ratio (OR)=3.7, P <0.0001] was significantly associated with an increased pCR rate, whereas tumor length > 4.85 cm was associated with pCR on univariate (OR=3.03, P <0.01) but not on multivariate analysis (OR=1.45, P =0.261). Other clinical parameters did not impact pCR rates. CONCLUSIONS A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR in locally advanced rectal cancer patients receiving neoadjuvant chemoradiation. Tumors above this volume threshold corresponded to a greater than 78% probability of not achieving pCR. This information will be helpful at diagnosis for clinicians who are considering potential candidates for NOM.
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Affiliation(s)
- Fan Yang
- Division of Radiation Oncology, Cross Cancer Institute
| | - Jordan Hill
- Division of Radiation Oncology, Cross Cancer Institute
| | - Aswin Abraham
- Division of Radiation Oncology, Cross Cancer Institute
| | - Sunita Ghosh
- Division of Radiation Oncology, Cross Cancer Institute
| | - Tanner Steed
- Division of Radiation Oncology, Cross Cancer Institute
| | - Clay Kurtz
- Undergraduate Medical Program, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Kurian Joseph
- Division of Radiation Oncology, Cross Cancer Institute
| | - Jihyun Yun
- Division of Radiation Oncology, Cross Cancer Institute
| | | | - JoAnn Thai
- Undergraduate Medical Program, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Tirath Nijjar
- Division of Radiation Oncology, Cross Cancer Institute
| | - Diane Severin
- Division of Radiation Oncology, Cross Cancer Institute
| | - Keith Tankel
- Division of Radiation Oncology, Cross Cancer Institute
| | | | - Nawaid Usmani
- Division of Radiation Oncology, Cross Cancer Institute
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Hsu YJ, Chern YJ, Lai IL, Chiang SF, Liao CK, Tsai WS, Hung HY, Hsieh PS, Yeh CY, Chiang JM, Yu YL, You JF. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy. Open Med (Wars) 2022; 17:1438-1448. [PMID: 36128450 PMCID: PMC9449684 DOI: 10.1515/med-2022-0555] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/26/2022] [Accepted: 08/02/2022] [Indexed: 12/04/2022] Open
Abstract
It is controversial whether patients who achieve clinical complete remission (cCR) of rectal cancer should be treated with the “watch and wait” (W&W) or radical resection (RR) strategy. Our study aimed to compare the survival outcomes and ostomy rate of the W&W and RR strategies. Between January 2008 and December 2015, we investigated 26 patients who achieved pathologic complete remission after undergoing RR and 36 patients who adopted the W&W strategy because of cCR. The tumor regrowth, salvage surgery, recurrence, disease-free, and overall survival (OS) rates were assessed. In our study, recurrences occurred in nine and two patients from the W&W and RR groups, respectively. Each patient in the RR group had a temporary or permanent ostomy, but only three (8.3%) had an ostomy in the W&W group. The 5-year recurrence rate was 25.0% in the W&W group and 7.7% in the RR group. Six patients (16.7%) had tumor regrowth in the W&W group, and all were resectable when regrowth. The 5-year OS rates between the two groups were nonsignificant. There is no specific risk factor for recurrence and OS. Under close surveillance, the W&W group achieved similar OS to the RR group and benefited from a lower ostomy rate.
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Affiliation(s)
- Yu-Jen Hsu
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Yih-Jong Chern
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - I-Li Lai
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Sum-Fu Chiang
- School of Traditional Chinese Medicine, Chang Gung University, Graduate Institute of Clinical Medical Sciences, Chang Gung University , Tao-Yuan , Taiwan
| | - Chun-Kai Liao
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Wen-Sy Tsai
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Hsin-Yuan Hung
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Pao-Shiu Hsieh
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Chien-Yuh Yeh
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Jy-Ming Chiang
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Guei-Shan , Tao-Yuan , Taiwan
| | - Yen-Lin Yu
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Keelung , Taiwan
| | - Jeng-Fu You
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Linko, 5, Fu-Hsing Street, Guei-Shan , Tao-Yuan , Taiwan
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Wang QX, Xiao BY, Cheng Y, Wu AW, Zhang T, Wang H, Zhang X, Huang WX, Tang JH, Jiang W, Steele SR, Krishnamurthi S, Li Y, Cai J, Kong LH, Li DD, Pan ZZ, Zhang XS, Ding PR. Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study. Eur J Cancer 2022; 174:176-184. [PMID: 36030556 DOI: 10.1016/j.ejca.2022.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 07/07/2022] [Accepted: 07/09/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND In a portion of patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer, clinical complete response (cCR) could be achieved after anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients. METHODS We retrospectively collected a series of patients with dMMR/MSI-H rectal adenocarcinoma who had cCR after receiving anti-PD-1 immunotherapy and adopted immunotherapy as curative-intent treatment from six institutions. Survival outcomes were analysed using the Kaplan-Meier method. RESULTS Nineteen patients were included with a median age of 48 (range 19-63). One patient was diagnosed with stage I disease, four with stage II disease and fourteen with stage III disease. Sixteen patients received anti-PD-1 immunotherapy as the first line of therapy, and eleven patients were treated with single-agent anti-PD-1 antibodies. The median time from the start of treatment to cCR was 3.8 (range 0.7-6.5) months. During a median follow-up of 17.1 (range 3.1-33.5) months since achieving cCR, no local or distant relapse was observed. Two-year local recurrence-free survival, distant metastasis-free survival, disease free-survival and overall survival for the whole cohort were 100%, 100%, 100% and 100%, respectively. CONCLUSIONS For patients with dMMR/MSI-H locally advanced rectal cancer who achieved cCR during anti-PD-1 immunotherapy, adopting immunotherapy as curative-intent treatment might be an alternative option. Longer follow-up and larger cohorts are warranted to verify this innovative treatment approach.
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Affiliation(s)
- Qiao-Xuan Wang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bin-Yi Xiao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ai-Wen Wu
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Tao Zhang
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Wang
- Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xuan Zhang
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wei-Xin Huang
- Department of Gastrointestinal Surgery, Honghe Prefecture Third People's Hospital, Honghe Cancer Hospital, Gejiu, China
| | - Jing-Hua Tang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wu Jiang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Scott R Steele
- Department of Colorectal Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, USA
| | - Smitha Krishnamurthi
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic Cleveland, OH, USA
| | - Yuan Li
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jian Cai
- Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ling-Heng Kong
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Dan-Dan Li
- Department of Biological Therapy Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Shi Zhang
- Department of Biological Therapy Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Leung G, Nishimura M, Hingorani N, Lin IH, Weiser MR, Garcia-Aguilar J, Pappou EP, Paty PB, Schattner MA. Technical feasibility of salvage endoscopic submucosal dissection after chemoradiation for locally advanced rectal adenocarcinoma. Gastrointest Endosc 2022; 96:359-367. [PMID: 35183541 DOI: 10.1016/j.gie.2022.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/09/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients. We aimed to evaluate the feasibility and safety of salvage ESD. METHODS A retrospective chart review of cases of salvage ESD for locally advanced rectal cancer and standard ESD for rectal tumors without prior CRT from July 2018 to August 2020 at our institution was performed. Clinical factors and imaging, procedural, and pathology results were collected and compared. RESULTS Twelve salvage ESD cases were compared with 27 standard ESD cases. Before CRT, 83.3% of lesions in the salvage ESD group were initially clinically staged as T3. The en-bloc resection rates were 92.7% and 91.7% (P = 1.00) and R0 resection rates 66.7% and 75.0% (P = .55) for the standard and salvage groups, respectively. In the salvage ESD group, no adverse events were observed, and 75.0% of the adenocarcinomas in the salvage ESD group had morphologically changed to hyperplasia or adenoma after CRT, with no identifiable lesions greater than T1 tumor depth. CONCLUSIONS Salvage ESD for locally advanced rectal cancer is technically feasible with low adverse event rates. There may be a diagnostic role in salvage ESD in assessing pathologic response to CRT and a possible therapeutic role in resection of residual lesions with the potential to avoid surgery.
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Affiliation(s)
- Galen Leung
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Makoto Nishimura
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Neha Hingorani
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - I-Hsin Lin
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Martin R Weiser
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Julio Garcia-Aguilar
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Emmanouil P Pappou
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Phillip B Paty
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mark A Schattner
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Wang QX, Zhang S, Xiao WW, Zhou CJ, Chang H, Zeng ZF, Cai PQ, Lu ZH, Chen G, Ding PR, Pan ZZ, Wu XJ, Gao YH. High dose chemoradiotherapy increases chance of organ preservation with satisfactory functional outcome for rectal cancer. Radiat Oncol 2022; 17:98. [PMID: 35585551 PMCID: PMC9118735 DOI: 10.1186/s13014-022-02066-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/09/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND High dose chemoradiotherapy offers a curative chance for patients with rectal cancer that are unfit or unwilling to undergo surgical resection, yet its long-term survival and functional outcomes have been rarely investigated. METHODS Patients with non-metastatic rectal adenocarcinoma who received pelvic radiation for curative intent from April 2006 to July 2017 were retrospectively investigated. Survival rates were analyzed using the Kaplan-Meier method. Quality of life and functional outcomes were evaluated using the EORTC quality of life questionnaire. RESULTS A total of 57 patients were included, with a median age of 59.0 (range, 29-84) years. The numbers of patients who were diagnosed as stage I, II and III were 5 (8.8%), 16 (28.1%) and 36 (63.2%), respectively. 53 (93.0%) patients had tumor located within 5 cm from the anal verge. All patients received fluorouracil-based concurrent chemoradiotherapy with a median radiation dose of 80 (range, 60-86) Gy. All kinds of grade 3-4 adverse events occurred in 18 (31.6%) patients. 42 (73.7%) patients achieved a clinical complete response after chemoradiotherapy. After a median follow-up of 43.5 (range 14.9-163.2) months, 12 (21.1%) patients had local progression and 11 (19.3%) developed distant metastasis. The 3-year local recurrence-free survival and distant metastasis-free survival were 77.3% (95% CI, 65.7-88.8%) and 79.2% (95% CI, 68.2-90.2%), while the 3-year progression-free survival, cancer-specific survival, overall survival were 61.9% (95% CI, 48.8-75.0%), 93.1% (95% CI, 85.8-100.0%) and 91.4% (95% CI, 83.6-99.2%), respectively. For patients who had tumor located within 3 cm from the anal verge, the sphincter preservation rate was 85.3% at last follow-up. Long-term adverse events mainly were anal blood loss. 21 patients completed the quality-of-life questionnaire and had a score of the global health status of 78.57 ± 17.59. Of them, 95.2% reported no urinary incontinence and 85.7% reported no fecal incontinence. CONCLUSIONS High dose chemoradiation demonstrated promising survival outcomes with acceptable short-term and long-term side effects, and satisfying long-term functional outcomes and quality of life. It could be considered as a non-invasive alternative for rectal cancer patients who refuse surgery.
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Affiliation(s)
- Qiao-Xuan Wang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Shu Zhang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Wei-Wei Xiao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Cheng-Jing Zhou
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Hui Chang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Zhi-Fan Zeng
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Pei-Qiang Cai
- Department of Medical Imaging and Interventional Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Zhen-Hai Lu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Gong Chen
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiao-Jun Wu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yuan-Hong Gao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
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Zwart WH, Hotca A, Hospers GAP, Goodman KA, Garcia-Aguilar J. The Multimodal Management of Locally Advanced Rectal Cancer: Making Sense of the New Data. Am Soc Clin Oncol Educ Book 2022; 42:1-14. [PMID: 35561302 DOI: 10.1200/edbk_351411] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In the past 40 years, the treatment of locally advanced rectal cancer has evolved with the addition of radiotherapy or chemoradiotherapy and providing (neo)adjuvant systemic chemotherapy to major surgery. However, recent trends have focused on improving our ability to risk-stratify patients and tailoring treatment to achieve the best oncologic outcome while limiting the impact on long-term quality of life. Therefore, there has been increasing interest in pursuing a watch-and-wait approach to achieve organ preservation. Several retro- and prospective studies suggest safety of the watch-and-wait approach, though it is still considered controversial due to limited clinical evidence, concerns about tumor regrowth, and subsequent distant progression. To further reduce treatment, MRI risk stratification, together with patient characteristics and patient preferences, can guide personalized treatment and reserve radiation and chemotherapy for a select patient population. Ultimately, improved options for reassessment during neoadjuvant treatment may allow for more adaptive therapy options based on treatment response. This article provides an overview of some major developments in the multimodal treatment of locally advanced rectal cancer. It reviews some relevant, controversial issues of the watch-and-wait approach and opportunities to personally tailor and reduce treatment. It also reviews the overall neoadjuvant treatment, including total neoadjuvant therapy trials, and how to best optimize for a potential complete response. Finally, it provides an algorithm as an example of how such a personalized, tailored, adaptive, and reduced treatment could look like in the future.
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Affiliation(s)
- Wouter H Zwart
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | | | - Geke A P Hospers
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Abstract
The treatment algorithm for locally advanced rectal cancer (LARC) has increased in complexity over the past 10 years. Nonoperative management (NOM) for rectal cancer in patients with clinical complete response (cCR) after neoadjuvant therapy has been gaining acceptance as a potential treatment option for selected LARC patients. The current challenge is to accurately select the patients with an apparent cCR, thereby correctly identifying those would-be appropriate candidates for a NOM strategy. NOM should be part of the treatment discussion of LARC, considering increasing rates of cCR, patient preference, potential quality of life gains, and the potential avoidance of surgical morbidity.
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Affiliation(s)
- Felipe F Quezada-Diaz
- Colorectal Unit, Department of Surgery, Complejo Asistencial Doctor Sótero del Río, Santiago, RM, Chile. https://twitter.com/ffquezad
| | - J Joshua Smith
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue
- SR-201, New York, NY 10065, USA.
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Hsu KS, Adileh M, Martin ML, Makarov V, Chen J, Wu C, Bodo S, Klingler S, Sauvé CEG, Szeglin BC, Smith JJ, Fuks Z, Riaz N, Chan TA, Nishimura M, Paty PB, Kolesnick R. Colorectal cancer develops inherent radiosensitivity that can be predicted using patient-derived organoids. Cancer Res 2022; 82:2298-2312. [PMID: 35472075 DOI: 10.1158/0008-5472.can-21-4128] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/21/2022] [Accepted: 04/22/2022] [Indexed: 11/16/2022]
Abstract
Identifying colorectal cancer patient populations responsive to chemotherapy or chemoradiation therapy before surgery remains a challenge. Recently validated mouse protocols for organoid irradiation employ the single hit multi-target (SHMT) algorithm, which yields a single value, the D0, as a measure of inherent tissue radiosensitivity. Here we translate these protocols to human tissue to evaluate radioresponsiveness of patient-derived organoids (PDOs) generated from normal human intestines and rectal tumors of patients undergoing neoadjuvant therapy. While PDOs from adenomas with a logarithmically-expanded Lgr5+-intestinal stem cell population retain the radioresistant phenotype of normal colorectal PDOs, malignant transformation yields PDOs from a large patient subpopulation displaying marked radiosensitivity due to reduced homologous recombination-mediated DNA repair. A proof-of-principle pilot clinical trial demonstrated that rectal cancer patient responses to neoadjuvant chemoradiation, including complete response, correlate closely with their PDO D0 values. Overall, upon transformation to colorectal adenocarcinoma, broad radiation sensitivity occurs in a large subset of patients that can be identified using SHMT analysis of PDO radiation responses.
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Affiliation(s)
- Kuo-Shun Hsu
- Memorial Sloan Kettering Cancer Center, New York City, United States
| | - Mohammad Adileh
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | | | - Vladimir Makarov
- Memorial Sloan Kettering Cancer Center, Cleveland, OH, United States
| | - Jiapeng Chen
- Memorial Sloan Kettering Cancer Center, Manhattan, New York, United States
| | - Chao Wu
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Sahra Bodo
- Memorial Sloan Kettering Cancer Center, New York, New York, United States
| | - Stefan Klingler
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | | | - Bryan C Szeglin
- Albert Einstein College of Medicine, Bronx, NY, United States
| | - J Joshua Smith
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Zvi Fuks
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Nadeem Riaz
- Memorial Sloan Kettering Cancer Center, Manhattan, New York, United States
| | | | - Makoto Nishimura
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Philip B Paty
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
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Fleischmann M, Diefenhardt M, Trommel M, Scherf C, Ramm U, Chatzikonstantinou G, Fokas E, Rödel C, Tselis N. Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach. Strahlenther Onkol 2022; 198:654-662. [PMID: 35445815 PMCID: PMC9217888 DOI: 10.1007/s00066-022-01931-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 03/10/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. METHODS Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1‑3, N0‑1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10-13 × 3 Gy EBRT followed by HDR-BT delivering 12-18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. RESULTS Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8-60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. CONCLUSION Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.
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Affiliation(s)
- Maximilian Fleischmann
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
| | - Markus Diefenhardt
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - Martin Trommel
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - Christian Scherf
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - Ulla Ramm
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - Georgios Chatzikonstantinou
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - Emmanouil Fokas
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Partner Site Frankfurt am Main, German Cancer Consortium (DKTK), Frankfurt, Germany
- Frankfurt Cancer Institute, Frankfurt, Germany
| | - Claus Rödel
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Partner Site Frankfurt am Main, German Cancer Consortium (DKTK), Frankfurt, Germany
- Frankfurt Cancer Institute, Frankfurt, Germany
| | - Nikolaos Tselis
- Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
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Yao L, Zao XL, Pan XF, Zhang HG, Wang FJ, Qiao PF. Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy. J Chemother 2022; 35:104-116. [PMID: 35285783 DOI: 10.1080/1120009x.2022.2045827] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.
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Affiliation(s)
- Lei Yao
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao-Long Zao
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao-Fei Pan
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hao-Gang Zhang
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fu-Jing Wang
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Peng-Fei Qiao
- Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Vatandoust S, Wattchow D, Sposato L, Michael MZ, Leung J, Gormly K, Chen G, Symonds EL, Tie J, Papanicolas LE, Woods S, Gebski V, Mead K, Kuruni A, Karapetis CS. A longitudinal cohort study of watch and wait in complete clinical responders after chemo-radiotherapy for localised rectal cancer: study protocol. BMC Cancer 2022; 22:222. [PMID: 35232427 PMCID: PMC8887187 DOI: 10.1186/s12885-022-09304-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/16/2022] [Indexed: 11/12/2022] Open
Abstract
Background Rectal Cancer is a common malignancy. The current treatment approach for patients with locally advanced rectal cancer involves neoadjuvant chemoradiotherapy followed by surgical resection of the rectum. The resection can lead to complications and long-term consequences. A clinical complete response is observed in some patients after chemoradiotherapy. A number of recent studies have shown that patients can be observed safely after completing chemoradiotherapy (without surgery), provided clinical complete response has been achieved. In this approach, resection is reserved for cases of regrowth. This is called the watch and wait approach. This approach potentially avoids unnecessary surgical resection of the rectum and the resulting complications. In this study, we will prospectively investigate this approach. Methods Adult patients with a diagnosis of rectal cancer planned to receive neoadjuvant long course chemoradiotherapy (± subsequent combination chemotherapy) will be consented into the study prior to commencing treatment. After completing the chemoradiotherapy (± subsequent combination chemotherapy), based on the clinical response, subjects will be allocated to one of the following arms: subjects who achieved a clinical complete response will be allocated to the watch and wait arm and others to the standard management arm (which includes resection). The aim of the study is to determine the rate of local failure and other safety and efficacy outcomes in the watch and wait arm. Patient reported outcome measures and the use of biomarkers as part of the clinical monitoring will be studied in both arms of the study. Discussion This study will prospectively investigate the safety of the watch and wait approach. We will investigate predictive biomarkers (molecular biomarkers and imaging biomarkers) and patient reported outcome measures in the study population and the cost effectiveness of the watch and wait approach. This study will also help evaluate a defined monitoring schedule for patients managed with the watch and wait approach. This protocol covers the first two years of follow up, we are planning a subsequent study which covers year 3–5 follow up for the study population. Trial registration. Name of the registry: Australia and New Zealand Clinical Trials Registry (ANZCTR). Trial registration number: Trial ID: ACTRN12619000207112 Registered 13 February 2019,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376810 Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09304-x.
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Affiliation(s)
- Sina Vatandoust
- Flinders Medical Centre, Adelaide, Australia. .,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia.
| | - David Wattchow
- Flinders Medical Centre, Adelaide, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia
| | - Luigi Sposato
- Flinders Medical Centre, Adelaide, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia
| | - Michael Z Michael
- Flinders Medical Centre, Adelaide, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia
| | - John Leung
- Flinders Medical Centre, Adelaide, Australia.,GenesisCare, Adelaide, Australia
| | - Kirsten Gormly
- Dr Jones & Partners Medical Imaging, Adelaide, Australia.,University of Adelaide, Adelaide, Australia
| | - Gang Chen
- Monash University, Melbourne, Australia
| | - Erin L Symonds
- Flinders Medical Centre, Adelaide, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia
| | - Jeanne Tie
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,Peter MacCallum Cancer Centre, Melbourne, Australia.,University of Melbourne, Melbourne, Australia
| | - Lito Electra Papanicolas
- Flinders Medical Centre, Adelaide, Australia.,South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Susan Woods
- University of Adelaide, Adelaide, Australia.,South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Val Gebski
- NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia
| | - Kelly Mead
- Flinders Medical Centre, Adelaide, Australia
| | | | - Christos S Karapetis
- Flinders Medical Centre, Adelaide, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia, 5042, Australia
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Kim JK, Thompson H, Jimenez-Rodriguez RM, Wu F, Sanchez-Vega F, Nash GM, Guillem JG, Paty PB, Wei IH, Pappou EP, Widmar M, Weiser MR, Smith JJ, Garcia-Aguilar J. Adoption of Organ Preservation and Surgeon Variability for Patients with Rectal Cancer Does Not Correlate with Worse Survival. Ann Surg Oncol 2022; 29:1172-1179. [PMID: 34601641 PMCID: PMC8727510 DOI: 10.1245/s10434-021-10877-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 09/04/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND OBJECTIVES Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compared the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS Overall, 444 locally advanced rectal cancer patients managed by five surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p = 0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that among expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.
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Affiliation(s)
- Jin K. Kim
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Hannah Thompson
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | - Fan Wu
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Francisco Sanchez-Vega
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA,Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Garrett M. Nash
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Jose G. Guillem
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Philip B. Paty
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Iris H. Wei
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Emmanouil P. Pappou
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Maria Widmar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Martin R. Weiser
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - J. Joshua Smith
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, USA
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Zhang X, Ding R, Li J, Wu T, Shen Z, Li S, Zhang Y, Dong C, Shang Z, Zhou H, Li T, Li G, Li Y. Efficacy and safety of the "watch-and-wait" approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a meta-analysis. Surg Endosc 2022; 36:2233-2244. [PMID: 34981233 DOI: 10.1007/s00464-021-08932-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 11/22/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Watch-and-Wait (WW) approach is positioned at the cutting edge of non-invasive approach for rectal cancer patients who achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). This meta-analysis aimed to compare the clinical, oncologic, and survival outcomes of WW versus radical surgery (RS) and to evaluate the efficacy, safety, and possible superiority of WW. METHODS A systematic search for studies comparing WW with RS was conducted on MEDLINE, Ovid, Embase, Cochrane Library, and Web of Science databases. After screening for inclusion, data extraction, and quality assessment, statistical analysis was performed using Stata/SE14.0 software. Permanent colostomy (PC), local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), 2-, 3-, and 5-year disease-free survival (DFS), and overall survival (OS) were analyzed using fixed effects or random-effects models depending on the heterogeneity. RESULTS Fourteen studies with moderate-high quality involving 1254 patients were included. Of these, 513 patients were managed with WW and 741 patients were subjected to RS. Compared to RS group, WW group had higher rate of LR (odds ratio OR = 11.09, 95% confidence interval CI = 5.30-23.20, P = 0.000), 2-year OS, and 3-year OS and had lower rate of PC (OR = 0.12, 95% CI = 0.05-0.29, P = 0.000). There were no significant between-group differences with respect to DM, CRD, 2-, 3-, and 5-year DFS (OR = 0.92, 95% CI = 0.81-1.03, P = 0.153), or 5-year OS (OR = 1.01, 95% CI = 0.28-3.63, P = 0.988). CONCLUSION The WW is a promising treatment approach and is a relatively safe alternative to RS for managing patients with rectal cancer who achieve cCR after nCRT. However, this modality requires rigorous screening criteria and standardized follow-up. Large-scale, multicenter prospective randomized controlled trials are warranted to further verify the outcomes of WW approach.
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Affiliation(s)
- Xuan Zhang
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China
| | - Rong Ding
- Department of Minimally Invasive Intervention, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, Kunming, 650118, People's Republic of China
| | - JinSha Li
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China
| | - Tao Wu
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China
| | - ZhengHai Shen
- Office of Cancer Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, People's Republic of China
| | - ShanShan Li
- Department of Anesthesiology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, Kunming, 650118, People's Republic of China
| | - Ya Zhang
- Department of Orthopaedics, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, Kunming, 650118, People's Republic of China
| | - Chao Dong
- Department of Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, Kunming, 650118, People's Republic of China
| | - ZhongJun Shang
- Department of Hospital Affairs, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, Kunming, 650118, People's Republic of China
| | - Hai Zhou
- Office of Cancer Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, People's Republic of China
| | - Ting Li
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China
| | - GuoYu Li
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China
| | - YunFeng Li
- Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519, Kunzhou Road, Xishan District, 650118, Yunnan, Kunming, People's Republic of China.
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Locally Advanced Rectal Cancer: What We Learned in the Last Two Decades and the Future Perspectives. J Gastrointest Cancer 2022; 54:188-203. [PMID: 34981341 DOI: 10.1007/s12029-021-00794-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2021] [Indexed: 12/13/2022]
Abstract
The advancement in surgical techniques, optimization of systemic chemoradiotherapy, and development of refined diagnostic and imaging modalities have brought a phenomenal shift in the treatment of the locally advanced rectal cancer. Although each therapeutic option has shown substantial progress in their field, it is finding their ideal amalgamation which has baffled the clinician and researchers alike. In the effort to identifying the perfect salutary treatment plan, we have even shifted our attention from the trimodal approach to non-operative "watchful waiting" to more recent individualized care. In this article, we acknowledge the scientific progress in the management of locally advanced rectal cancer and compare the opportunities as well as the obstacles while implementing them clinically. We also explore the current challenges and controversies surrounding the multidisciplinary approach and highlight the new trends and recent advances with an ultimate goal to improve the patients' quality of life.
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50
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Eng C, Jácome AA, Agarwal R, Hayat MH, Byndloss MX, Holowatyj AN, Bailey C, Lieu CH. A comprehensive framework for early-onset colorectal cancer research. Lancet Oncol 2022; 23:e116-e128. [PMID: 35090673 DOI: 10.1016/s1470-2045(21)00588-x] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 02/07/2023]
Abstract
Sporadic colorectal cancer has traditionally been viewed as a malignancy of older individuals. However, as the global prevalence of the disease diagnosed in younger individuals (<50 years) is expected to increase within the next decade, greater recognition is now being given to early-onset colorectal cancer. The cause of the predicted rise in prevalence is largely unknown and probably multifactorial. In this Series paper, we discuss the potential underlying causes of early-onset colorectal cancer, the role of energy balance, biological and genomic mechanisms (including microbiome aspects), and the treatment of early-onset colorectal cancer. We have specifically considered the psychosocial challenges of being diagnosed with colorectal cancer at younger age and the potential financial toxicity that might ensue. This Series paper brings a comprehensive review based on the existing data in the hopes of optimising the overall outcomes for patients with early-onset colorectal cancer.
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