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Tang M, Liu S, Li W, Peng X, Wang Y, Chen Y, Yang D, Xiang T, Wu Z. Prognostic value of albumin-to-alkaline phosphatase ratio and CONUT score in rectal cancer patients undergoing XELOX-based chemotherapy: development of a nomogram-based predictive model. Am J Cancer Res 2025; 15:1578-1596. [PMID: 40371163 PMCID: PMC12070095 DOI: 10.62347/hsde2538] [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: 01/06/2025] [Accepted: 04/03/2025] [Indexed: 05/16/2025] Open
Abstract
OBJECTIVE To evaluate the prognostic significance of the albumin-to-alkaline phosphatase ratio (AAPR) and the Controlling Nutritional Status (CONUT) score in rectal cancer (RC) patients receiving XELOX-based chemotherapy, and to develop a nomogram for predicting recurrence risk. METHODS This retrospective study included 389 RC patients treated at the First Affiliated Hospital of Chongqing Medical University, along with an independent validation cohort of 120 patients. Clinical variables, including AAPR and CONUT were analyzed using Cox regression and cumulative incidence function curves. A nomogram was constructed and validated using calibration plots and time-dependent receiver operating characteristic (ROC) curves. RESULTS Both AAPR (HR = 0.073, P<0.001) and CONUT score (HR = 1.497, P<0.001) were identified as independent predictors of recurrence. Additional factors significantly associated with increased recurrence risk included TNM stage III, tumor size ≥5 cm, vascular invasion, and carcinoembryonic antigen (CEA) level ≥5 ng/ml. The nomogram demonstrated strong predictive performance with a C-index of 0.860 in the training cohort, and 0.835 in the validation cohort. Calibration plots showed excellent agreement between predicted and observed recurrence probabilities. CONCLUSIONS AAPR and CONUT score are independent prognostic indicators for recurrence in RC patients treated with XELOX-based chemotherapy. The proposed nomogram, incorporating these variables, provides a reliable tool for individualized risk prediction and may support personalized treatment decision-making.
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Affiliation(s)
- Min Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China
- Department of Oncology, Chongqing General Hospital, Chongqing UniversityChongqing 401120, China
| | - Shuang Liu
- Department of Ultrasound, Women and Children’s Hospital of Chongqing Medical UniversityChongqing 401147, China
| | - Wenbo Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China
| | - Xi Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China
| | - Yu Wang
- Department of Hepatic Biliary and Pancreatic Cancer Center, Chongqing University Cancer HospitalChongqing 400030, China
| | - Yinghua Chen
- Department of Oncology and Hematology, Chongqing University Central HospitalChongqing 400010, China
| | - Dan Yang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Department of Medical Oncology, Chongqing University Cancer HospitalChongqing 400030, China
| | - Tingxiu Xiang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing 400030, China
| | - Zhongjun Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016, China
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Bunjo Z, Sammour T. Early-stage low rectal cancer - re-thinking the standard of care. ANZ J Surg 2025. [PMID: 40231801 DOI: 10.1111/ans.70139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 04/05/2025] [Accepted: 04/07/2025] [Indexed: 04/16/2025]
Affiliation(s)
- Zachary Bunjo
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - Tarik Sammour
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
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Moretto R, Boccaccio C, Landi M, Masi G, Cremolini C. Total neoadjuvant treatment, non-operative management and radiotherapy-free strategies: New approaches for the management of proficient mismatch repair/microsatellite stable locally advanced rectal cancer. A narrative review and evidence-based algorithm. Eur J Cancer 2025; 218:115261. [PMID: 39908654 DOI: 10.1016/j.ejca.2025.115261] [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: 11/26/2024] [Revised: 01/17/2025] [Accepted: 01/21/2025] [Indexed: 02/07/2025]
Abstract
In recent years, new therapeutic approaches have emerged in addition to classical neoadjuvant (chemo)radiotherapy for the treatment of locally advanced rectal cancer (LARC): total neoadjuvant treatment, non-operative management, and radiotherapy-free strategy. While the introduction of these approaches in a relatively short timeframe has quickly increased our therapeutic armamentarium, on the other hand it has complicated the decision-making process regarding the choice of the most appropriate treatment strategy for each patient with LARC. Therefore, a tool to interpret the evidence from clinical trials and to translate them into daily practice is highly demanded. In the present review, we address how these new developments are changing the multimodal treatment of LARC and offer an algorithm to integrate them into clinical practice.
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Affiliation(s)
- Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Chiara Boccaccio
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Matteo Landi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
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4
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Wo JY, Ashman JB, Bhadkamkar NA, Bradfield L, Chang DT, Hanna N, Hawkins M, Holtz M, Kim E, Kelly P, Ling DC, Olsen JR, Palta M, Raldow AC, Ruiz-Garcia E, Sheybani A, Stitzenberg KB, Das P. Radiation Therapy for Rectal Cancer: An ASTRO Clinical Practice Guideline Focused Update. Pract Radiat Oncol 2025; 15:124-143. [PMID: 39603501 DOI: 10.1016/j.prro.2024.11.003] [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: 10/08/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024]
Abstract
PURPOSE With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer. METHODS The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations. CONCLUSIONS The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.
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Affiliation(s)
- Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
| | | | - Nishin A Bhadkamkar
- Department of General Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lisa Bradfield
- American Society for Radiation Oncology, Arlington, Virginia
| | - Daniel T Chang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Nader Hanna
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Michael Holtz
- Patient Representative, Oak Ridge Associated Universities, Knoxville, Tennessee
| | - Edward Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington
| | - Patrick Kelly
- Department of Radiation Oncology, Orlando Health, Orlando, Florida
| | - Diane C Ling
- Department of Radiation Oncology, University of Southern California, Los Angeles, California
| | - Jeffrey R Olsen
- Department of Radiation Oncology, University of Colorado, Aurora, Colorado
| | - Manisha Palta
- Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina
| | - Ann C Raldow
- Department of Radiation Oncology, University of Southern California, Los Angeles, California
| | - Erika Ruiz-Garcia
- Department of Medical Oncology, Instituto Nacional de Cancerologia, Mexico City, Mexico
| | - Arshin Sheybani
- Department of Radiation Oncology, UnityPoint Health, Des Moines, Iowa
| | - Karyn B Stitzenberg
- Department of Surgery, University of North Carolina, Chapel Hill, North Carolina
| | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
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Mohammed H, Mohamed H, Mohamed N, Sharma R, Sagar J. Early Rectal Cancer: Advances in Diagnosis and Management Strategies. Cancers (Basel) 2025; 17:588. [PMID: 40002183 PMCID: PMC11853685 DOI: 10.3390/cancers17040588] [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: 12/29/2024] [Revised: 02/07/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Colorectal cancer (CRC) is the second most prevalent cause of cancer-related death and the third most common cancer globally. Early-stage rectal cancer is defined by lesions confined to the bowel wall, without extension beyond the submucosa in T1 or the muscularis propria in T2, with no indication of lymph node involvement or distant metastasis. The gold standard for managing rectal cancer is total mesorectal excision (TME); however, it is linked to considerable morbidities and impaired quality of life. There is a growing interest in local resection and non-operative treatment of early RC for organ preservation. Local resection options include three types of transanal endoscopic surgery (TES): transanal endoscopic microsurgery (TEM), transanal endoscopic operations (TEO), and transanal minimally invasive surgery (TAMIS), while endoscopic resection includes endoscopic mucosal resection (EMR), underwater endoscopic mucosal resection (UEMR), and endoscopic submucosal dissection (ESD). Although the oncological outcome of local resection of early rectal cancer is debated in the current literature, some studies have shown comparable outcomes with radical surgery in selected patients. The use of adjuvant and neoadjuvant chemoradiotherapy in early rectal cancer management is also controversial in the literature, but a number of studies have reported promising outcomes. This review focuses on the available literature regarding diagnosis, staging, and management strategies of early rectal cancer and provides possible recommendations.
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Affiliation(s)
- Huda Mohammed
- Surgery Department, Colorectal Surgery, Luton and Dunstable Hospital, Luton LU4 0DZ, UK; (H.M.); (N.M.); (R.S.)
| | - Hadeel Mohamed
- Faculty of Medicine, University of Khartoum, Khartoum 11115, Sudan;
| | - Nusyba Mohamed
- Surgery Department, Colorectal Surgery, Luton and Dunstable Hospital, Luton LU4 0DZ, UK; (H.M.); (N.M.); (R.S.)
| | - Rajat Sharma
- Surgery Department, Colorectal Surgery, Luton and Dunstable Hospital, Luton LU4 0DZ, UK; (H.M.); (N.M.); (R.S.)
| | - Jayesh Sagar
- Surgery Department, Colorectal Surgery, Luton and Dunstable Hospital, Luton LU4 0DZ, UK; (H.M.); (N.M.); (R.S.)
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Ben Dhia S, Chauviere D, Mitrea D, Schiappa R, Pace Loscos T, Chamorey E, Baron D. Organ preservation, for rectal cancer: general overview of the latest data from phase III randomized trials. Acta Oncol 2025; 64:120-128. [PMID: 39871514 PMCID: PMC11794997 DOI: 10.2340/1651-226x.2025.41057] [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: 06/25/2024] [Accepted: 01/09/2025] [Indexed: 01/29/2025]
Abstract
INTRODUCTION Organ preservation (OP) strategies are gaining interest in improving the quality of life in the management of rectal cancer, particularly for tumors located in the distal or middle rectum. The optimal OP protocol is still not standardized and relies on randomized trials. This review summarizes past and ongoing studies on OP protocols for adenocarcinoma of the distal and middle rectum. METHOD We searched for articles and abstracts on randomized clinical trials investigating OP approaches for rectal cancer, including data presented at the LUCARRE Congress held in Nice on November 25, 2023, covering ongoing and recently published trials on rectal preservation. RESULTS Our review's findings are presented in four tables: the first evaluates key trials with overall survival (OS) as the primary endpoint; the second provides an overview of past Phase III trials; the third reviews Phase II/III trials that specifically focus on local excisions (LE); and finally, the fourth summarizes ongoing trials. Each table is accompanied by detailed comments elucidating the significance and implications of the presented data, alongside a review of current guidelines. INTERPRETATION We highlight the growing interest in OP strategies for rectal cancer management to enhance patients' quality of life. Despite the lack of international consensus on the optimal OP protocol, past and ongoing randomized trials provide valuable findings into the evolving management strategies of rectal cancer treatment. The presented data supports the role of randomized phase III trials to provide evidence for a change in clinical practice.
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Affiliation(s)
- Syrine Ben Dhia
- Department of Radiotherapy, Antoine Lacassagne Center, Nice, France.
| | - Damien Chauviere
- Department of Clinical Research and Innovation, Antoine Lacassagne Center, Nice, France
| | - Diana Mitrea
- Department of Radiotherapy, Antoine Lacassagne Center, Nice, France
| | - Renaud Schiappa
- Department of Epidemiology, Biostatistics and Health Data, Centre Antoine Lacassagne, University of Côte d'Azur, Nice, France
| | - Tanguy Pace Loscos
- Department of Epidemiology, Biostatistics and Health Data, Centre Antoine Lacassagne, University of Côte d'Azur, Nice, France
| | - Emmanuel Chamorey
- Department of Epidemiology, Biostatistics and Health Data, Centre Antoine Lacassagne, University of Côte d'Azur, Nice, France
| | - David Baron
- Department of Radiotherapy, Antoine Lacassagne Center, Nice, France
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7
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Brennan KE, Farooq AO, Mckechnie TJ, Wiseman VH, Kong W, Bankhead CR, Heneghan CJ, Rai MS, Patel SV. Local excision for T1 rectal cancer: A population-based study of practice patterns and oncological outcomes. Colorectal Dis 2025; 27:e17276. [PMID: 39797387 PMCID: PMC11724163 DOI: 10.1111/codi.17276] [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: 05/25/2024] [Revised: 09/20/2024] [Accepted: 11/18/2024] [Indexed: 01/13/2025]
Abstract
AIM Local excision (LE) for T1 rectal cancer may be recommended in those with low-risk disease, while resection is typically recommended in those with a high risk of luminal recurrence or lymph node metastasis. The aim of this work was to compare survival between resection and LE. METHOD This was a population-based retrospective cohort study set in the Canadian province of Ontario. Patients were individuals with T1Nx rectal cancer between 2010 and 2014 and demographics, disease characteristics, treatments and outcomes were determined using linked administrative databases. This study does not include clinical information regarding individual patient treatment decisions. The main outcome measure was overall survival (OS). RESULTS A total of 719 patients were identified, including 359 with upfront resection, 113 with LE and immediate resection (<90 days) and 247 with LE with definitive intent. The majority of LEs were performed via colonoscopy. Piecemeal excision (42% vs. 49%, p = 0.28) and positive margin (50% vs. 77%, p < 0.01) rates were high in both LE groups, with the highest rate in those with immediate resection. The prevalence of poor differentiation (<5%, p = 0.70) and lymphovascular invasion (LVI) (14%, p = 0.80) was similar across groups. In those with LE with definitive intent, 21% ultimately underwent resection (median 150 days, interquartile range 114-181 days) and 4% received radiation. There was no difference in 5-year OS between groups (resection 83.2% vs. LE and immediate resection 82.3% vs. definitive LE 83.3%; p = 0.33). Adjusted analyses demonstrated no association between approach and survival [definitive intent LE hazard ratio (HR) 0.97 (95% CI 0.70-1.35), LE and immediate resection HR 0.97 (95% CI 0.60-1.45), upfront resection HR 1 (Ref); p = 0.98]. Differentiation, piecemeal excisions and LVI were not associated with OS in the LE groups. CONCLUSION There were no observed differences in survival between those who underwent resection, LE and immediate resection and definitive intent LE. Although, these are observational data, they call into question the reflexive decision to offer radical resection for those with suspected T1 rectal cancer.
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Affiliation(s)
- Kelly E. Brennan
- Division of General Surgery, Department of SurgeryQueen's UniversityKingstonOntarioCanada
| | - Ameer O. Farooq
- Division of General Surgery, Department of SurgeryQueen's UniversityKingstonOntarioCanada
| | - Tyler J. Mckechnie
- Division of General Surgery, Department of SurgeryMcMaster UniversityHamiltonOntarioCanada
| | - Vanessa H. Wiseman
- Division of General Surgery, Department of SurgeryQueen's UniversityKingstonOntarioCanada
| | - Weidong Kong
- Cancer Care and EpidemiologyQueen's UniversityKingstonOntarioCanada
| | | | | | - Mandip S. Rai
- Division of Gastroenterology, Department of MedicineQueen's UniversityKingstonOntarioCanada
| | - Sunil V. Patel
- Division of General Surgery, Department of SurgeryQueen's UniversityKingstonOntarioCanada
- Cancer Care and EpidemiologyQueen's UniversityKingstonOntarioCanada
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8
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Dhimal T, Hilty Chu BK, Loria A, Boyer M, Cai X, Li Y, Colugnati F, Cupertino P, Ramsdale EE, Fleming FJ. Contemporary practices in abdominoperineal resection for early-stage rectal cancer in the United States. Colorectal Dis 2025; 27:e17281. [PMID: 39746870 DOI: 10.1111/codi.17281] [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] [Received: 06/13/2024] [Revised: 10/09/2024] [Accepted: 12/02/2024] [Indexed: 01/04/2025]
Abstract
AIM In contrast to significant advances in organ preservation in locally advanced rectal cancer, the contemporary management of early-stage rectal cancer, including the frequency of abdominoperineal resections, remains largely unexplored in the United States. Therefore, we assessed the utilization of neoadjuvant therapy and oncological resections in early-stage rectal cancer patients. STUDY DESIGN This is a retrospective cohort study of patients with cT1-T3N0 rectal cancer who underwent proctectomies between 2016 and 2022 in the National Surgical Quality Improvement Project proctectomy files. Multivariable logistic regression was used to identify factors associated with abdominoperineal resections and Kendall's tau statistics to evaluate clinical-pathological staging agreement. RESULTS In all, 3078 patients (29.6% cT1-2N0, 70.4% cT3N0) were included with 55.3% of tumours <5 cm from the anal verge. Overall, 58.2% received neoadjuvant therapy within 3 months of surgery (30.6% for cT1-T2N0 vs. 69.8% for cT3N0, P < 0.001), and 58.6% underwent abdominoperineal resection (55.5% for cT1-T2N0 vs. 59.9% for cT3N0, P = 0.058). The adjusted odds of undergoing abdominoperineal resection were associated with increasing age (OR 1.4 per every 10-year increase; 95% CI 1.2-1.5), cT3N0 tumours (OR 1.7; 95% CI 1.1-2.7) and tumour location <5 cm from the anal verge (OR 10.6; 95% CI 7.7-14.7). There was a weak clinical-pathological T staging correlation (Kendal tau coefficient 0.25; 95% CI 0.20-0.29). CONCLUSION In this large cohort of patients with early-stage rectal cancer with high rates of neoadjuvant therapy, over half of patients underwent abdominoperineal resection and one in five had a pathological complete response. These findings underscore opportunities for organ preservation in early-stage rectal cancer, suggesting that treatments typically reserved for locally advanced disease may extend to early stages with the completion of ongoing clinical trials.
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Affiliation(s)
- Totadri Dhimal
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
| | - Bailey K Hilty Chu
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
| | - Anthony Loria
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
| | - Megan Boyer
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
| | - Xueya Cai
- Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA
| | - Yue Li
- Division of Health Policy and Outcomes Research, Department of Public Health Sciences, University of Rochester Medical Center, Rochester, New York, USA
| | - Fernando Colugnati
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
- School of Medicine, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
| | - Paula Cupertino
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
| | - Erika E Ramsdale
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, USA
| | - Fergal J Fleming
- Department of Surgery, Surgical Health Outcomes and Research Enterprise (SHORE), University of Rochester Medical Center, Rochester, New York, USA
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9
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Anker CJ, Tchelebi LT, Selfridge JE, Jabbour SK, Akselrod D, Cataldo P, Abood G, Berlin J, Hallemeier CL, Jethwa KR, Kim E, Kennedy T, Lee P, Sharma N, Small W, Williams VM, Russo S. Executive Summary of the American Radium Society on Appropriate Use Criteria for Nonoperative Management of Rectal Adenocarcinoma: Systematic Review and Guidelines. Int J Radiat Oncol Biol Phys 2024; 120:946-977. [PMID: 38797496 DOI: 10.1016/j.ijrobp.2024.05.019] [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: 01/24/2024] [Revised: 04/15/2024] [Accepted: 05/17/2024] [Indexed: 05/29/2024]
Abstract
For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values.
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Affiliation(s)
- Christopher J Anker
- Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont
| | - Leila T Tchelebi
- Northwell, New Hyde Park, New York; Department of Radiation Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
| | - J Eva Selfridge
- Division of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, New Jersey
| | - Dmitriy Akselrod
- Department of Radiology, University of Vermont Larner College of Medicine, Burlington, Vermont
| | - Peter Cataldo
- Department of Surgery, University of Vermont Larner College of Medicine, Burlington, Vermont
| | - Gerard Abood
- Department of Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois
| | - Jordan Berlin
- Division of Hematology Oncology, Department of Medicine Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | | | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, New Jersey
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, California
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, Pennsylvania
| | - William Small
- Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois
| | - Vonetta M Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, New York
| | - Suzanne Russo
- Department of Radiation Oncology, MetroHealth, Case Western Reserve University School of Medicine, Cleveland, Ohio
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10
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Garfinkle RC, McKenna NP. Low Anterior Resection Syndrome following Restorative Proctectomy for Rectal Cancer: Can the Surgeon Have Any Meaningful Impact? Cancers (Basel) 2024; 16:2307. [PMID: 39001370 PMCID: PMC11240414 DOI: 10.3390/cancers16132307] [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: 06/05/2024] [Revised: 06/20/2024] [Accepted: 06/22/2024] [Indexed: 07/16/2024] Open
Abstract
Postoperative bowel dysfunction following restorative proctectomy, commonly referred to as Low Anterior Resection Syndrome (LARS), is a common long term sequela of rectal cancer treatment. While many of the established risk factors for LARS are non-modifiable, others may be well within the surgeon's control. Several pre-, intra-, and postoperative decisions may have a significant impact on postoperative bowel function. Some of these factors include the extent of surgical resection, surgical approach, choice of anastomotic reconstruction, and use of fecal diversion. This review article summarizes the available evidence regarding how surgical decision-making can affect postoperative bowel function.
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Affiliation(s)
| | - Nicholas P. McKenna
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA;
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11
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Jiang SX, Zarrin A, Shahidi N. T1 colorectal cancer management in the era of minimally invasive endoscopic resection. World J Gastrointest Oncol 2024; 16:2284-2294. [PMID: 38994167 PMCID: PMC11236244 DOI: 10.4251/wjgo.v16.i6.2284] [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: 12/29/2023] [Revised: 04/02/2024] [Accepted: 04/24/2024] [Indexed: 06/13/2024] Open
Abstract
T1 colorectal cancer (CRC), defined by tumor invasion confined to the submucosa, has historically been managed by surgery. Improved understanding of recurrence and lymph node metastases risk, coupled with advances in endoscopic resection techniques, have led to an increasing capacity for organ-sparing local excision. Minimally invasive management of T1 CRC begins with optical evaluation of the lesion to diagnose invasive disease and quantify depth of invasion, which informs therapeutic decision making. Modality selection between various available endoscopic resection techniques depends upon lesion characteristics, technique risk-benefit profiles, and location-specific implications. Following endoscopic resection, established histopathology features determine the risk of recurrence and subsequent management including surveillance or adjuvant surgical excision. The management of non-operative candidates deviates from conventional recommendations with emerging treatment strategies in select populations.
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Affiliation(s)
- Shirley Xue Jiang
- Department of Medicine, University of British Columbia, Vancouver V6Z2K5, British Columbia, Canada
| | - Aein Zarrin
- Department of Medicine, University of British Columbia, Vancouver V6Z2K5, British Columbia, Canada
| | - Neal Shahidi
- Department of Medicine, University of British Columbia, Vancouver V6Z2K5, British Columbia, Canada
- Division of Gastroenterology, St. Paul’s Hospital, Vancouver V6Z2K5, British Columbia, Canada
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12
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O’Donnell CDJ, Hubbard J, Jin Z. Updates on the Management of Colorectal Cancer in Older Adults. Cancers (Basel) 2024; 16:1820. [PMID: 38791899 PMCID: PMC11120096 DOI: 10.3390/cancers16101820] [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: 04/09/2024] [Revised: 05/04/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Colorectal cancer (CRC) poses a significant global health challenge. Notably, the risk of CRC escalates with age, with the majority of cases occurring in those over the age of 65. Despite recent progress in tailoring treatments for early and advanced CRC, there is a lack of prospective data to guide the management of older patients, who are frequently underrepresented in clinical trials. This article reviews the contemporary landscape of managing older individuals with CRC, highlighting recent advancements and persisting challenges. The role of comprehensive geriatric assessment is explored. Opportunities for treatment escalation/de-escalation, with consideration of the older adult's fitness level. are reviewed in the neoadjuvant, surgical, adjuvant, and metastatic settings of colon and rectal cancers. Immunotherapy is shown to be an effective treatment option in older adults who have CRC with microsatellite instability. Promising new technologies such as circulating tumor DNA and recent phase III trials adding later-line systemic therapy options are discussed. Clinical recommendations based on the data available are summarized. We conclude that deliberate efforts to include older individuals in future colorectal cancer trials are essential to better guide the management of these patients in this rapidly evolving field.
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Affiliation(s)
- Conor D. J. O’Donnell
- Mayo Clinic School of Graduate Education, Mayo Clinic College of Medicine and Science, Mayo Building, Rochester, MN 55905, USA;
| | - Joleen Hubbard
- Allina Health Cancer Institute, Minneapolis, MN 55407, USA
| | - Zhaohui Jin
- Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
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13
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Binda C, Secco M, Tuccillo L, Coluccio C, Liverani E, Jung CFM, Fabbri C, Gibiino G. Early Rectal Cancer and Local Excision: A Narrative Review. J Clin Med 2024; 13:2292. [PMID: 38673565 PMCID: PMC11051053 DOI: 10.3390/jcm13082292] [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: 03/20/2024] [Revised: 04/03/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
A rise in the incidence of early rectal cancer consequent to bowel-screening programs around the world and an increase in the incidence in young adults has led to a growing interest in organ-sparing treatment options. The rectum, being the most distal portion of the large intestine, is a fertile ground for local excision techniques performed with endoscopic or surgical techniques. Moreover, the advancement in endoscopic optical evaluation and the better definition of imaging techniques allow for a more precise local staging of early rectal cancer. Although the local treatment of early rectal cancer seems promising, in clinical practice, a significant number of patients who could benefit from local excision techniques undergo total mesorectal excision (TME) as the first approach. All relevant prospective clinical trials were identified through a computer-assisted search of the PubMed, EMBASE, and Medline databases until January 2024. This review is dedicated to endoscopic and surgical local excision in the treatment of early rectal cancer and highlights its possible role in current and future clinical practice, taking into account surgical completion techniques and chemoradiotherapy.
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Affiliation(s)
| | | | | | | | | | | | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, AUSL Romagna, 47121 Forlì, Italy; (C.B.); (M.S.); (L.T.); (C.C.); (E.L.); (C.F.M.J.); (G.G.)
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14
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Glimelius B. Recent advances in rectal cancer treatment - are we on the right track? Ups J Med Sci 2024; 129:10537. [PMID: 38449909 PMCID: PMC10916366 DOI: 10.48101/ujms.v129.10537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 01/25/2024] [Accepted: 01/25/2024] [Indexed: 03/08/2024] Open
Abstract
Background Staging and treatment of rectal cancer have evolved over several decades with considerably fewer locoregional recurrences but no marked improved survival since systemic recurrence risks remain virtually unchanged. This development will briefly be summarised followed by a thorough discussion of two recent developments. Methods A systematic approach towards the literature is aimed at focusing on organ preservation and the delivery of all non-surgical treatments prior to surgery or total neoadjuvant treatment (TNT). Results Organ preservation, that is to defer surgery if the tumour happens to disappear completely after any pre-treatment given to locally advanced tumours to decrease recurrence risks has increased in popularity and is, if not universally, widely accepted. To give neo-adjuvant treatment to intentionally obtain a clinically complete remission to avoid surgery is practised in some environments but is mostly still experimental. TNT, that is to provide both radiotherapy and chemotherapy aimed at killing microscopic disease in the pelvis or elsewhere has been subject to several trials. Collectively, they show that the chance of achieving a complete response, pathologically or clinically, has approximately doubled, increasing the chance for organ preservation, and the risk of distant metastasis has decreased at least in some trials. The best schedule remains to be established. Conclusions To obtain substantial progress and also improve survival, the systemic treatments need to be improved even if preoperative delivery is more effective and better tolerated than postoperative. The locoregional treatment may be further optimised through better risk prediction.
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Affiliation(s)
- Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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Abstract
Nonoperative treatment of rectal cancer is gaining popularity. Several trials recently demonstrated advantages in disease-free survival with total neoadjuvant treatment (TNT) with the addition of the watch and wait (WW) strategy for locally advanced rectal cancer. On longer follow-up, an unexpected increased risk in local recurrence in the TNT group at the RAPIDO trial suggested early surgery for nonresponding tumours. The WW option is globally accepted for a complete clinical response; however, a high rate of regrowth was found in a registry with an increased risk of distant metastases, questioning the deleterious effect of deferral of surgery in this group. The short- and long-term toxic effects of neoadjuvant treatment are costs to consider in the National Comprehensive Cancer Network guidelines compared with the European Society for Medical Oncology guidelines, which favour surgery alone if good mesorectal resection is assured with increasing surgical proficiency adjusted to the precise anatomical location.
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Affiliation(s)
- Julio S Leite
- Department of Surgery, Coimbra University Hospital, Coimbra, Portugal
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Wojcieszynski AP, Chuong MD, Hawkins M, Jethwa KR, Kim H, Raldow A, Sanford NN, Olsen JR. Rectal Cancer Update: Which Treatment Effects Are the Least "Brutal"? Int J Radiat Oncol Biol Phys 2024; 118:1-7. [PMID: 38049215 DOI: 10.1016/j.ijrobp.2023.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/04/2023] [Accepted: 08/06/2023] [Indexed: 12/06/2023]
Affiliation(s)
| | - Michael D Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida
| | | | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Hyun Kim
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri
| | - Ann Raldow
- Department of Radiation Oncology, University of California, Los Angeles, California
| | - Nina N Sanford
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas
| | - Jeffrey R Olsen
- Department of Radiation Oncology, University of Colorado, Denver, Colorado.
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17
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Kwik C, El-Khoury T, Pathma-Nathan N, Toh JWT. Endoscopic and trans-anal local excision vs. radical resection in the treatment of early rectal cancer: A systematic review and network meta-analysis. Int J Colorectal Dis 2023; 39:13. [PMID: 38157077 DOI: 10.1007/s00384-023-04584-6] [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: 12/21/2023] [Indexed: 01/03/2024]
Abstract
PURPOSE The management of early-stage rectal cancer in clinical practice is controversial. The aim of this network meta-analysis was to compare oncological and postoperative outcomes for T1T2N0M0 rectal cancers managed with local excision in comparison to conventional radical resection. METHODS A systematic review of Medline, Embase and Cochrane electronic databases was performed. Relevant studies were selected using PRISMA guidelines. The primary outcomes measured were 5-year local recurrence and overall survival. Secondary outcomes included rates of postoperative complication, 30-day mortality, positive margin and permanent stoma formation. RESULTS Three randomized controlled trials and 27 observational studies contributed 8570 patients for analysis. Radical resection was associated with reduced 5-year local recurrence in comparison to local excision. This was statistically significant in comparison to trans-anal local excision (odds ratio (OR) 0.23; 95% confidence interval 0.16-0.30) and favourable in comparison to endoscopic techniques (OR 0.40; 95% confidence interval 0.13-1.23) although this did not reach clinical significance. Positive margin rates were lowest for radical resection. However, 30-day mortality rates, perioperative complications and permanent stoma rates all favoured local excision with no statistically significant difference between endoscopic and trans-anal techniques. CONCLUSION Radical resection of early rectal cancer is associated with the lowest 5-year local recurrence rates and the lowest rate of positive margins. However, this must be balanced with its higher 30-day mortality and complication rates as well as the increased risk of permanent stoma. The emerging potential role of neoadjuvant therapy prior to local resection, and the heterogeneity of its use, as an alternative treatment for early rectal cancer further complicates the treatment paradigm and adds to controversy in this field.
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Affiliation(s)
- Charlotte Kwik
- Department of Colorectal Surgery, Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, NSW, Australia.
| | - Toufic El-Khoury
- Department of Colorectal Surgery, Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, NSW, Australia
| | - Nimalan Pathma-Nathan
- Department of Colorectal Surgery, Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, NSW, Australia
| | - James Wei Tatt Toh
- Department of Colorectal Surgery, Westmead Hospital, Cnr Hawkesbury Road and Darcy Road, Westmead, NSW, Australia.
- Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
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Kennecke HF, Auer R, Cho M, Dasari NA, Davies-Venn C, Eng C, Dorth J, Garcia-Aguilar J, George M, Goodman KA, Kreppel L, Meyer JE, Monzon J, Saltz L, Schrag D, Smith JJ, Zell JA, Das P. NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer. J Natl Cancer Inst 2023; 115:1457-1464. [PMID: 37535679 PMCID: PMC11032701 DOI: 10.1093/jnci/djad143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/17/2023] [Accepted: 06/21/2023] [Indexed: 08/05/2023] Open
Abstract
The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.
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Affiliation(s)
- Hagen F Kennecke
- Medical Oncology, Providence Cancer Institute Franz Clinic, Portland, OR, USA
| | | | - May Cho
- University of CA–Irvine, Irvine, CA, USA
| | - N Arvind Dasari
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Cathy Eng
- Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jennifer Dorth
- University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | | | - Manju George
- Paltown Development Foundation, Crownsville, MD, USA
| | | | | | | | | | - Leonard Saltz
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Deborah Schrag
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - J Joshua Smith
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Prajnan Das
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Lynch P, Ryan OK, Donnelly M, Ryan ÉJ, Davey MG, Reynolds IS, Creavin B, Hanly A, Kennelly R, Martin ST, Winter DC. Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials. Int J Colorectal Dis 2023; 38:263. [PMID: 37924372 DOI: 10.1007/s00384-023-04558-8] [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: 10/26/2023] [Indexed: 11/06/2023]
Abstract
INTRODUCTION Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.
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Affiliation(s)
- Paul Lynch
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Odhrán K Ryan
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Mark Donnelly
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Éanna J Ryan
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
| | - Matthew G Davey
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Ian S Reynolds
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Ben Creavin
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Ann Hanly
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Rory Kennelly
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Seán T Martin
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Des C Winter
- Department of Colorectal Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
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Rouanet P, Castan F, Mazard T, Lemanski C, Nougaret S, Deshayes E, Chalbos P, Gourgou S, Taoum C. GRECCAR 14 - a multicentric, randomized, phase II-III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol. Colorectal Dis 2023; 25:2078-2086. [PMID: 37697712 DOI: 10.1111/codi.16740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/27/2023] [Accepted: 08/03/2023] [Indexed: 09/13/2023]
Abstract
AIM Total neoadjuvant treatment (TNT) is becoming standard in patients with locally advanced rectal carcinoma (LARC). Preoperative chemoradiotherapy (CRT) has proven side effects on bowel and genitourinary function. An early tumoral response to induction chemotherapy demonstrates its high prognostic value. Tailored management could be used as an alternative to systematic CRT. The GRECCAR 14 trial will attempt to personalize treatment strategy according to the patient's early tumour response to intensive chemotherapy with the aim of achieving the best toxicity-efficiency ratio. METHOD GRECCAR 14 is a multicentric, randomized, two-arm, phase II-III noninferiority trial. Patients with mid or low LARC with a predictive circumferential resection margin ≤2 mm or T3c-d stage with extramural venous invasion will be included. Evaluation of the tumoral response will be performed after six courses of high-dose FOLFIRINOX chemotherapy. Good responders (GRs) will be defined by a 60% decrease in tumoral volume on magnetic resonance imaging. Patients will be randomized to CRT before surgery. The primary endpoints will be R0 resection for phase II and the 3-year disease-free survival (DFS) for phase III. RESULTS Tailored management of LARC is becoming an exciting challenge for the modality of neoadjuvant treatment and for the type of surgery or its omission. Neoadjuvant FOLFIRINOX has established efficacy, with a significant increase in the 3-year DFS. Better control of systemic disease must be accompanied by the same locoregional control, with the lowest morbidity. Our previous GRECCAR 4 trial demonstrated the high value of the early tumoral response after induction chemotherapy and the long-term safety of tailored management for GRs. CONCLUSION If GRECCAR 14 demonstrates the ability to tailor TNT for LARC, this could lead to changes in clinical practice.
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Affiliation(s)
- Philippe Rouanet
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Florence Castan
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Thibault Mazard
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Claire Lemanski
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | | | - Emmanuel Deshayes
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Patrick Chalbos
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Sophie Gourgou
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Christophe Taoum
- Institut régional du Cancer de Montpellier (ICM), Montpellier, France
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21
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Paroder V, Fraum TJ, Nougaret S, Petkovska I, Rauch GM, Kaur H. Key clinical trials in rectal cancer shaping the current treatment paradigms: reference guide for radiologists. Abdom Radiol (NY) 2023; 48:2825-2835. [PMID: 37221342 DOI: 10.1007/s00261-023-03931-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 04/18/2023] [Accepted: 04/18/2023] [Indexed: 05/25/2023]
Abstract
Total neoadjuvant therapy (TNT), which includes chemotherapy and radiation prior to surgical resection, has been recently accepted as the new standard of care for patients with locally advanced low and mid rectal cancers. Multiple clinical trials have evaluated this approach in the last several decades and demonstrated improvement in, local control and reduced risk of recurrence. In addition, in the course of these investigations, it has been shown that between a third and a half of patients experience a clinical complete response (cCR) after being treated with the TNT approach, leading to the development of new organ preservation protocol, now known as watch-and-wait (W&W). On this protocol, cCR patients are not referred for surgery after total neoadjuvant treatment. Instead, they remain on close surveillance and, thus, avoid potential complications associated with surgical resection. Multiple clinical trials are ongoing, investigating the long-term outcomes of these new approaches and the development of less toxic and more effective TNT regimens for LARC. Improvements in technology and rectal MRI protocols position radiologists as vital members of multidisciplinary rectal cancer management teams. Rectal MRI has become a critical tool for rectal cancer initial staging, treatment response assessment, and surveillance on W&W protocols. In this review, we summarize the findings of the pivotal clinical trials that contributed to establishing the current treatment paradigms in locally advanced rectal cancer (LARC) management, with the intention of helping radiologists play more effective roles in their multidisciplinary teams.
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Affiliation(s)
- Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Tyler J Fraum
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA
| | - Stephanie Nougaret
- Department of Radiology, Montpellier Cancer Institute (ICM), Montpellier, France
| | - Iva Petkovska
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Gaiane M Rauch
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Harmeet Kaur
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Xiong X, Wang C, Cao J, Gao Z, Ye Y. Lymph node metastasis in T1-2 colorectal cancer: a population-based study. Int J Colorectal Dis 2023; 38:94. [PMID: 37055602 DOI: 10.1007/s00384-023-04386-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/26/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. METHODS The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. RESULTS Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. CONCLUSION Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue.
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Affiliation(s)
- Xiaoyu Xiong
- Department of Gastroenterological Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Chao Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Jian Cao
- Department of Gastroenterological Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - Zhidong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
| | - Yingjiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
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Li W, Xiang XX, Da Wang H, Cai CJ, Cao YH, Liu T. Transanal endoscopic microsurgery versus radical resection for early-stage rectal cancer: a systematic review and meta- analysis. Int J Colorectal Dis 2023; 38:49. [PMID: 36800079 PMCID: PMC9938057 DOI: 10.1007/s00384-023-04341-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 02/18/2023]
Abstract
PURPOSE In the treatment of early-stage rectal cancer, a growing number of studies have shown that transanal endoscopic microsurgery is one of the alternatives to radical surgery adhering to total mesorectal excision that can reduce the incidence of adverse events without compromising treatment outcomes. The purpose of this meta-analysis is to compare the safety and treatment effect of transanal endoscopic microsurgery and radical surgery adhering to total mesorectal excision to provide a basis for clinical treatment selections. METHOD We searched the literatures of four major databases, PubMed, Embase, Web of science, and Cochrane Library, without limitation of time. The literatures included randomized controlled studies and cohort studies comparing two surgical procedures of transanal endoscopic microsurgery and radical surgery adhering to total mesorectal excision. Treatment effectiveness and safety results of transanal endoscopic microsurgery and radical surgery were extracted from the included literatures and statistically analyzed using RevMan5.4 and stata17. RESULT Ultimately, 13 papers were included in the study including 5 randomized controlled studies and 8 cohort studies. The results of the meta-analysis showed that the treatment effect and safety of both transanal endoscopic microsurgery and radical surgery in distant metastasis (RR, 0.59 (0.34, 1.02), P > 0.05), overall recurrence (RR, 1.49 (0.96, 2.31), P > 0.05), disease-specific-survival (RR, 0.74 (0.09, 1.57), P > 0.05), dehiscence of the sutureline or anastomosis leakage (RR, 0.57 (0.30, 1.06), P > 0.05), postoperative bleeding (RR, 0.47 (0.22, 0.99), P > 0.05), and pneumonia (RR, 0.37, (0.10, 1.40), P > 0.05) were not significantly different. However, they differ significantly in perioperative mortality (RR, 0.26 (0.07, 0.93, P < 0.05)), local recurrence (RR, 2.51 (1.53, 4.21), P < 0.05),_overall survival_ (RR, 0.88 (0.74, 1.00), P < 0.05), disease-free-survival (RR, 1.08 (0.97, 1.19), P < 0.05), temporary stoma (RR, 0.05 (0.01, 0.20), P < 0.05), permanent stoma (RR, 0.16 (0.08, 0.33), P < 0.05), postoperative complications (RR, 0.35 (0.21, 0.59), P < 0.05), rectal pain (RR, 1.47 (1.11, 1.95), P < 0.05), operation time (RR, -97.14 (-115.81, -78.47), P < 0.05), blood loss (RR, -315.52 (-472.47, -158.57), P < 0.05), and time of hospitalization (RR, -8.82 (-10.38, -7.26), P < 0.05). CONCLUSION Transanal endoscopic microsurgery seems to be one of the alternatives to radical surgery for early-stage rectal cancer, but more high-quality clinical studies are needed to provide a reliable basis.
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Affiliation(s)
- Wei Li
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan , Hubei Province, 430022, China
| | - Xing Xing Xiang
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan , Hubei Province, 430022, China
| | - Hong Da Wang
- Department of Trauma Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan , Hubei Province, 430022, China
| | - Chen Jun Cai
- Department of Trauma Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan , Hubei Province, 430022, China
| | - Ying Hao Cao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Tao Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Šemanjski K, Lužaić K, Brkić J. Current Surgical Methods in Local Rectal Excision. Gastrointest Tumors 2023; 10:44-56. [PMID: 39015761 PMCID: PMC11249472 DOI: 10.1159/000538958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 04/10/2024] [Indexed: 07/18/2024] Open
Abstract
Background The treatment of rectal cancer has evolved with the advancement of surgical techniques. Less invasive approaches are becoming more accepted as the primary treatment method. Summary Such methods as transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery can reduce morbidity and mortality rates. However, not all patients are suitable candidates for these procedures, and proper diagnostics are necessary to establish indications. Compared to total mesorectal excision, transanal excision techniques have been shown to have fewer complications and comorbidities while still being able to remove cancerous tissue entirely. Transanal excision is the simplest method, where the operator removes visible rectal lesions. The basic principle of transanal endoscopic microsurgery is to dilate the rectum mechanically and by air insufflation and then use special surgical instruments to remove suspicious lesions under the vision of a telescope. Transanal minimally invasive surgery combines transanal endoscopic microsurgery and single-incision laparoscopic surgery, making the hard-to-reach proximal rectum accessible to classic laparoscopic instruments. Key Message Local excision techniques, when used as a monotherapy for treating patients with rectal cancer, have established themselves as a curative and less radical treatment for strictly selected patients with early rectal carcinoma, leading to improved quality of life. When combined with other modalities such as neoadjuvant chemoradiotherapy, total neoadjuvant therapy, and immunotherapy, transanal surgery can be offered to patients with locally advanced rectal cancer as part of the organ preservation strategy. This review will discuss the patient selection and technical aspects of transanal surgery, showcasing its current role in treating rectal carcinoma.
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Affiliation(s)
| | - Karla Lužaić
- Institute of Emergency Medicine of Sisak - Moslavina County, Sisak, Croatia
| | - Jure Brkić
- Department of Surgery, Clinical Hospital Sveti Duh, Zagreb, Croatia
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Rumpold H, Wolf D. Editorial: Current innovations in GI-oncology: Where do we stand? Front Oncol 2022; 12:1048082. [DOI: 10.3389/fonc.2022.1048082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 09/30/2022] [Indexed: 11/13/2022] Open
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