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Timmermans QMMA, de Hingh IHJT, Elferink MAG, Wijnhoven BPL, Schoon EJ, de Wilt JHW, van der Geest LGM, Vissers PAJ. Trends in resection rates and postoperative mortality for gastrointestinal cancers between 2005 and 2020 in the Netherlands. Eur J Cancer 2025; 222:115469. [PMID: 40315591 DOI: 10.1016/j.ejca.2025.115469] [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: 01/10/2025] [Revised: 04/17/2025] [Accepted: 04/18/2025] [Indexed: 05/04/2025]
Abstract
AIM This study assesses trends in resection rates and postoperative mortality for oesophageal, gastric, colon, rectal, periampullary and pancreatic cancer in the Netherlands. METHODS This retrospective cohort study included all patients with gastrointestinal cancer diagnosed in the period 2005-2020 as registered in the Netherlands Cancer Registry. Cochran-Armitage trend tests were used to assess trends in resection rates. Multivariable logistic regression analyses were used to assess the association between time period and resection rates and postoperative mortality and were stratified for nonmetastatic versus metastatic disease at initial diagnosis. RESULTS A total of 226 925 patients with nonmetastatic and 92 343 with metastatic disease were included. A lower likelihood of undergoing resection was observed for patients diagnosed between 2017 and 2020 as compared to 2005-2008 for nonmetastatic colon (OR=0.73; 95 %CI:0.68-0.79) and rectal cancer (OR=0.44; 95 %CI:0.40-0.48). In contrast, higher resection rates were observed for nonmetastatic gastric (OR=1.17; 95 %CI:1.03-1.32), periampullary (OR=2.44;95 %CI:2.09-2.84) and pancreatic cancer (OR=2.81; 95 %CI:2.51-3.15 comparing the same time periods). Patients with nonmetastatic disease diagnosed in 2017-2020 had a lower likelihood of 90-day postoperative mortality compared to 2005-2008 for all cancer types with ORs ranging between 0.27 (95 %CI:0.22-0.33, rectal cancer) and 0.60 (95 %CI:0.43-0.84, periampullary cancer). In colon and rectal cancer patients presenting with metastatic disease, resection rates and postoperative mortality significantly decreased over time. CONCLUSION Resection rates decreased for some gastrointestinal cancer types possibly due to the introduction of treatment strategies without resection (e.g. watchful waiting). Postoperative mortality decreased for all patients, possibly as a result of increased quality of care, and improved patient selection.
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Affiliation(s)
| | | | - Marloes A G Elferink
- Department of Research and Development, Netherlands comprehensive Cancer organization (IKNL), Utrecht, the Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus University Medical Centre, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Erik J Schoon
- GROW, Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lydia G M van der Geest
- Department of Research and Development, Netherlands comprehensive Cancer organization (IKNL), Utrecht, the Netherlands
| | - Pauline A J Vissers
- Department of Research and Development, Netherlands comprehensive Cancer organization (IKNL), Utrecht, the Netherlands; Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands.
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Ang ZH, Wong SW. Management of the Malignant Rectal Polyp-A Narrative Review. Cancers (Basel) 2025; 17:1464. [PMID: 40361391 PMCID: PMC12071011 DOI: 10.3390/cancers17091464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 04/20/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
PURPOSE The aim of this review is to provide a contemporary update on the current management approaches and options with specific considerations in malignant rectal polyps. METHODS A literature review was carried out in PubMed, Embase and Cochrane databases using the keywords "malignant" and "polyp*". Only publications in English language were included. RESULTS Histopathological features including margins, depth of invasion, tumour grade, LVI and tumour budding determines the risk of lymph node metastasis in malignant polyps. Rectal malignant polyps should be considered differently compared to their colonic counterpart. A low threshold should be considered for utilising transrectal excision to fully excise the polyp and to assess the margins. The rates of complete pathological response associated with total neoadjuvant therapy as well as the advent of "watch and wait" adds to the complexity of managing malignant rectal polyps. CONCLUSIONS The management of malignant colorectal polyps lies in risk-stratifying patients who will benefit from an oncological resection.
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Affiliation(s)
- Zhen Hao Ang
- Department of Colorectal Surgery, Prince of Wales Hospital, Sydney, NSW 2031, Australia;
- Randwick Campus, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
| | - Shing Wai Wong
- Department of Colorectal Surgery, Prince of Wales Hospital, Sydney, NSW 2031, Australia;
- Randwick Campus, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
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3
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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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ACCORD study: a national multi-centre study of the watch and wait approach in patients with rectal cancer in Aotearoa New Zealand. ANZ J Surg 2025; 95:440-449. [PMID: 40071714 DOI: 10.1111/ans.19415] [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] [Revised: 12/21/2024] [Accepted: 01/10/2025] [Indexed: 03/27/2025]
Abstract
AIM The adoption of a watch and wait (W&W) approach in patients with rectal cancer, and a complete clinical response (cCR) following neoadjuvant therapy, is increasing worldwide. Despite this, pragmatic unbiased outcome data is limited. This study aimed to investigate national outcomes associated with W&W in Aotearoa New Zealand (AoNZ). METHODS A national retrospective study of patients with adenocarcinoma of the rectum managed with a W&W approach between January 2015 and December 2022 in AoNZ was performed by STRATA, a student and trainee led collaborative network. The Cancer Registry and the New Zealand Ministry of Health National Minimum Data Set were linked to identify patients who had rectal cancer and who were treated with neoadjuvant therapy but not rectal resection. Research teams across 17 AoNZ hospitals then screened these patients for inclusion and data collection. RESULTS One thousand five hundred and eighteen patients were screened across 17 hospitals, 133 met inclusion criteria. Median age was 71 years. Median follow-up was 2.2 years. The 2-year cumulative incidence of local regrowth was 18.2% (95% CI 10.7%-25.1%), of which 92% was present in the bowel wall, and 68% underwent surgery, all with curative intent. The 2-year cumulative distant metastasis rate was 8.8% (95% CI 3.0%-14.2%) and the 2-year overall survival was 94.8% (95% CI 90.4%-99.4%). CONCLUSION This nationwide study of a W&W approach has clinical outcomes similar to the international literature. This data will help guide further implementation of a W&W approach in the management of patients with rectal cancer and inform both clinicians and patients.
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Gandini A, Sciallero S, Martelli V, Pirrone C, Puglisi S, Cremante M, Grassi M, Andretta V, Fornarini G, Caprioni F, Comandini D, Pessino A, Mammoliti S, Sobrero A, Pastorino A. A Comprehensive Approach to Neoadjuvant Treatment of Locally Advanced Rectal Cancer. Cancers (Basel) 2025; 17:330. [PMID: 39858112 PMCID: PMC11763976 DOI: 10.3390/cancers17020330] [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: 12/10/2024] [Revised: 01/14/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025] Open
Abstract
At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2-3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Alessandro Pastorino
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (A.G.)
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6
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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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Than NW, Pritchard DM, Hughes DM, Duckworth CA, Wong H, Ul Haq M, Sripadam R, Myint AS. Contact X-ray Brachytherapy as a Boost Therapy After Neoadjuvant (Chemo)Radiation in High-Risk Locally Advanced Rectal Cancer. Int J Radiat Oncol Biol Phys 2024:S0360-3016(24)03720-9. [PMID: 39674328 DOI: 10.1016/j.ijrobp.2024.11.113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 11/04/2024] [Accepted: 11/29/2024] [Indexed: 12/16/2024]
Abstract
PURPOSE Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A contact x-ray brachytherapy (CXB) boost can alternatively be used to treat residual disease postneoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low- to intermediate-risk patients. We have now evaluated the utility of CXB boost in high-risk rectal cancers after their tumors have been significantly downstaged by neoadjuvant (chemo)radiation. MATERIALS AND METHODS Oncological outcomes and treatment tolerability were evaluated in 328 patients based on rectal cancer treatment risk stratification: low-/intermediate-risk (cT1-3ab, N0-1, M0, no extramural venous invasion, mesorectal fascia involvement >1 mm) and high-risk (cT3cd-4/N2, M0, mesorectal fascia ≤1 mm, and/or extramural venous invasion positive). RESULTS With a median follow-up of 33 (IQR, 15-54) months and a median age of 73 (IQR, 62-80) years, no significant differences were found between low/intermediate and high-risk groups in clinical complete response (78% vs. 73%, P = .32), local regrowth (16.6% vs. 22.4%, P = .41), nodal (1.8% vs. 5.8%, P = .051) or regional (1.3% vs. 2.9%, P = .33) relapse, or postradiation toxicities (P = .16). However, the high-risk group had a higher distant relapse rate (21.2% vs. 10.7%, P = .01), with no significant differences in 3-year organ preservation (80% vs. 87%, P = .25), 5-year disease-free survival (62% vs. 64%, P = .46), or overall survival (67% vs. 64%, P = .88). Longer treatment time, treatment gap >24 weeks between therapies, and administration of a higher than standard CXB dose were newly identified factors that negatively impacted outcomes. CONCLUSIONS High-risk patients with rectal cancer treated with CXB boost had more distant relapses, but comparable locoregional tumor control, organ preservation, disease-free survival, and overall survival to lower risk patients, with acceptable toxicities. CXB boost is, therefore, a viable option for selected high-risk patients with rectal cancer. Timely reassessment, prompt referral, and CXB dose optimization are crucial for improving outcomes.
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Affiliation(s)
- Ngu Wah Than
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool; Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom
| | - D Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool
| | - David M Hughes
- Department of Health Data Science, Institute of Population Health, The University of Liverpool, Liverpool, United Kingdom
| | - Carrie A Duckworth
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool
| | - Helen Wong
- Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom
| | - Muneeb Ul Haq
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool; Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom
| | - Rajaram Sripadam
- Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom
| | - Arthur Sun Myint
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, The University of Liverpool; Papillon Suite, The Clatterbridge Cancer Centre National Health Service Foundation Trust, Bebington, Wirral, United Kingdom.
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8
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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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9
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Burger JWA, Grotenhuis BA. Neoadjuvant treatment of rectal cancer: from adjunct to surgery to primary organ sparing treatment. Br J Surg 2024; 111:znae300. [PMID: 39699219 DOI: 10.1093/bjs/znae300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 11/06/2024] [Indexed: 12/20/2024]
Affiliation(s)
- Jacobus W A Burger
- Department of Surgical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Brechtje A Grotenhuis
- Department of Surgical Oncology, National Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands
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Tribonias G, Papaefthymiou A, Zormpas P, Seewald S, Zachou M, Barbaro F, Kahaleh M, Andrisani G, Elkholy S, El-Sherbiny M, Komeda Y, Yarlagadda R, Tziatzios G, Essam K, Haggag H, Paspatis G, Mavrogenis G. Endoscopic Local Excision (ELE) with Knife-Assisted Resection (KAR) Techniques Followed by Adjuvant Radiotherapy and/or Chemotherapy for Invasive (T1bsm2,3/T2) Early Rectal Cancer: A Multicenter Retrospective Cohort. J Clin Med 2024; 13:6951. [PMID: 39598095 PMCID: PMC11594537 DOI: 10.3390/jcm13226951] [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: 09/17/2024] [Revised: 11/02/2024] [Accepted: 11/16/2024] [Indexed: 11/29/2024] Open
Abstract
Background: Resected rectal polyps with deep invasion into the submucosa (pT1b-sm2,3) or the muscle layer (pT2) are currently confronted with surgery due to non-curative resection. Aims: We evaluated the efficacy, safety, and locoregional control of adjuvant radiotherapy (RT) and/or chemotherapy (CT) following endoscopic KAR (knife-assisted resection) in patients with invasive early rectal cancers who are unwilling or unsuitable for additional surgical resection. Methods: Fifty-one patients with early rectal cancers, pT1b or pT2, underwent post-resection adjuvant RT and/or CT in 15 centers worldwide. "En bloc" macroscopic resection, R0 resection, recurrence rate, and adverse events following resection and adjuvant therapy were recorded in a multicenter retrospective cohort study. Results: Diagnostic staging (38/51, 75%) was the main reason for ELE. Macroscopic "en bloc" resection was demonstrated in 50/51 (98%), with an average follow-up of 20.6 months. Endoscopic recurrence occurred in 7/51 (13.7%) of patients, with mean time for diagnosis of recurrence at 8.9 months. Adjuvant therapy consisted of RT in 49.0% (25/51), CT in 11.8% (6/51), and combined CRT in 39.2% (20/51) of the cases. Perforation, severe post-procedural bleeding, and incontinence were the most frequent complications. The absence of superficial ulceration was associated with macroscopic complete resection, while the lesions with lower budding stage, clear lateral margins, lesion size < 40 mm, and needle-type knife used were associated with less endoscopic recurrencies. Conclusions: Our data investigated adjuvant RT and/or CT after endoscopic KAR of infiltrative rectal cancers (pT1bsm2,3-pT2) as being safe and effective for locoregional control and providing a non-surgical treatment option for patients with a non-curative resection.
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Affiliation(s)
- George Tribonias
- Department of Gastroenterology, Red Cross Hospital, 11526 Athens, Greece
| | | | - Petros Zormpas
- Department of Gastroenterology, Red Cross Hospital, 11526 Athens, Greece
| | - Stefan Seewald
- Center for Gastroenterology, Hirslanden Clinic Zurich, 8032 Zurich, Switzerland
| | - Maria Zachou
- Department of Gastroenterology, “Sismanogleio” General Hospital, 15126 Athens, Greece
| | - Federico Barbaro
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Michel Kahaleh
- Department of Gastroenterology, Rutgers Robert Wood Johnson Medical School New Brunswick, New Brunswick, NJ 08901, USA
| | - Gianluca Andrisani
- Digestive Endoscopy Unit, Campus Bio-Medico, University of Rome, 00128 Rome, Italy
| | - Shaimaa Elkholy
- Gastroenterology Division, Internal Medicine Department, Faculty of Medicine, Cairo University Kasr Alainy, Cairo 4240310, Egypt
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh 13713, Saudi Arabia
| | - Yoriaki Komeda
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka-Sayama 589-0014, Japan
| | | | - Georgios Tziatzios
- Department of Gastroenterology, “Konstantopoulio-Patision” General Hospital, 14233 Athens, Greece
| | - Kareem Essam
- Gastroenterology Division, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 4240310, Egypt
| | - Hany Haggag
- Gastroenterology Division, Internal Medicine Department, Faculty of Medicine, Cairo University Kasr Alainy, Cairo 4240310, Egypt
| | - Gregorios Paspatis
- Department of Gastroenterology, Venizeleion General Hospital, 71409 Heraklion, Greece
| | - Georgios Mavrogenis
- Unit of Hybrid Interventional Endoscopy, Department of Gastroenterology, Mediterraneo Hospital, 16675 Athens, Greece
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11
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Grotenhuis BA, Couwenberg AM, Marijnen CAM. TNT for organ preservation in rectal cancer: still looking for the right schedule and patient. Ann Oncol 2024; 35:928-929. [PMID: 39461746 DOI: 10.1016/j.annonc.2024.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 09/18/2024] [Indexed: 10/29/2024] Open
Affiliation(s)
- B A Grotenhuis
- Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam
| | - A M Couwenberg
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam
| | - C A M Marijnen
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam; Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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12
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Rao C, Sun Myint A. Watch and Wait is Changing: We Need to Change How We Count Costs. Ann Surg Oncol 2024; 31:7673-7675. [PMID: 39222299 DOI: 10.1245/s10434-024-16175-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 08/24/2024] [Indexed: 09/04/2024]
Affiliation(s)
- Christopher Rao
- Department of Colorectal Surgery, North Cumbria Integrated Care NHS Foundation Trust, Carlisle, UK.
- Department of Surgery and Cancer, Imperial College London, London, UK.
| | - Arthur Sun Myint
- The Clatterbridge Cancer Centre, Liverpool, UK
- University of Liverpool, Liverpool, UK
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13
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Geubels BM, van den Esschert AJ, Temmink SJD, Nilsson PJ, Martling A, Roodvoets AGH, Peeters KCMJ, Sonneveld DJA, van Westreenen HL, Bujko K, Melenhorst J, Burger JWA, Talsma AK, Malcomson L, Peters FP, Beets GL, Grotenhuis BA. Outcomes of watch and wait after short-course radiotherapy in an international multicentre watch-and-wait cohort. Br J Surg 2024; 111:znae242. [PMID: 39392106 DOI: 10.1093/bjs/znae242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/09/2024] [Accepted: 08/29/2024] [Indexed: 10/12/2024]
Affiliation(s)
- Barbara M Geubels
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
| | | | - Sofieke J D Temmink
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Per J Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Annet G H Roodvoets
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | - Koen C M J Peeters
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | | | | | - Krzysztof Bujko
- Department of Radiation Oncology, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland
| | - Jarno Melenhorst
- Department of Surgery, Maastricht University Hospital, Maastricht, The Netherlands
| | | | - A Koen Talsma
- Department of Surgery, Deventer Hospital, Deventer, The Netherlands
| | - Lee Malcomson
- Department of Surgery, The Christie NHS Foundation Trust, Manchester, UK
| | - Femke P Peters
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Geerard L Beets
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands
- GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
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14
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R SB, Sarin A, Aggarwal S, Halder S, Hukku S, Mustafa T, Arora V, Malik VK, Singh S, Rao GV, Saklani A, Bhojwani R, Rawat S, Selvasekar C, Parikh PM. Neoadjuvant Treatment in Rectal Cancer. South Asian J Cancer 2024; 13:274-280. [PMID: 40060347 PMCID: PMC11888809 DOI: 10.1055/s-0045-1802334] [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: 04/02/2025] Open
Abstract
A major advance in rectal cancer was the evidence supporting short-course radiotherapy and long-course chemoradiotherapy. Both have been shown to improve local outcomes. Total neoadjuvant therapy (TNT) is the new kid on the block that provides further benefit of improving local responses as well as reducing systemic relapses, thus increasing overall survival. Details of the four key TNT trials are discussed. They pave the way for nonoperative management for patients who achieve clinical complete responses.
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Affiliation(s)
- Srinath Bhradwaj R
- Department of Medical Oncology, Apollo Cancer Institutes, Hyderabad, Telangana, India
| | - Aditya Sarin
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - Shyam Aggarwal
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - Shikha Halder
- Department of Radiation Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - S Hukku
- Department of Radiation Oncology, BLK Max Hospital, New Delhi, India
| | - Taha Mustafa
- Department of Colo Rectal Surgery, Sir Ganga Ram Hospital, New Delhi, India
| | - Vijay Arora
- Department of Laparoscopic Surgery, Sir Ganga Ram Hospital, New Delhi, India
| | - V K Malik
- Department of Laparoscopic Surgery, Sir Ganga Ram Hospital, New Delhi, India
| | | | - G V Rao
- Department of Gastrointestinal and Minimally Invasive Surgery, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Avinash Saklani
- Department of Colorectal Surgery, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Rajesh Bhojwani
- Department of Surgical Gastroenterology, Santokba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India
| | - Saumitra Rawat
- Department of Surgical Gastroenterology, SGRH, New Delhi, India
| | - C Selvasekar
- Clinical Services and Specialist Surgery, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Purvish M Parikh
- Department of Clinical Hematology, Sri Ram Cancer Center, Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan, India
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15
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Duggan WP, Lenihan J, Clancy C, McNamara DA, Burke JP. The effect of implementing a transanal minimally invasive surgical programme for the local excision of early rectal neoplasia on outcomes in a tertiary referral rectal cancer centre. Eur J Gastroenterol Hepatol 2024; 36:861-866. [PMID: 38625823 DOI: 10.1097/meg.0000000000002773] [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: 04/18/2024]
Abstract
Transanal minimally invasive surgery (TAMIS) is a surgical alternative to proctectomy in the management of complex rectal polyps and early rectal cancers. In 2016, our institution introduced a TAMIS programme. The purpose of this study was to evaluate changes in practice and outcomes in our institution in the 3 years before and after the implementation of TAMIS. We conducted a retrospective analysis of a prospective database of patients who underwent proctectomy or TAMIS for the management of complex rectal polyps or early rectal cancers at our institution between 2013 and 2018. 96 patients were included in this study (41 proctectomy vs 55 TAMIS). A significant reduction was noted in the number of proctectomies performed in the 3 years after the implementation of TAMIS as compared to the 3 years before (13 vs 28) ( P < 0.001); 43% of patients ( n = 12) who underwent proctectomy in the period prior to implementation of TAMIS were American Society of Anaesthesiologists grade III, as compared to only 15% ( n = 2) of patients during the period following TAMIS implementation ( P = 0.02). TAMIS was associated with a significant reduction in length of inpatient stay ( P < 0.001). Oncological outcomes were comparable between groups (log rank P = 0.83). Our findings support TAMIS as a safe and effective alternative to radical resection. The availability of TAMIS has resulted in a significant reduction in the number of comorbid patients undergoing proctectomy at our institution. Consequently, we have observed a significant reduction in postoperative complications over this time period.
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Affiliation(s)
- William P Duggan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - John Lenihan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin
| | - Cillian Clancy
- Department of Colorectal Surgery, Beaumont Hospital, Dublin
| | | | - John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin
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16
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Ghosh NK, Kumar A. Ultra-minimally invasive endoscopic techniques and colorectal diseases: Current status and its future. Artif Intell Gastrointest Endosc 2024; 5:91424. [DOI: 10.37126/aige.v5.i2.91424] [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: 12/28/2023] [Revised: 04/12/2024] [Accepted: 05/06/2024] [Indexed: 05/11/2024] Open
Abstract
Colorectal diseases are increasing due to altered lifestyle, genetic, and environmental factors. Colonoscopy plays an important role in diagnosis. Advances in colonoscope (ultrathin scope, magnetic scope, capsule) and technological gadgets (Balloon assisted scope, third eye retroscope, NaviAid G-EYE, dye-based chromoendoscopy, virtual chromoendoscopy, narrow band imaging, i-SCAN, etc.) have made colonoscopy more comfortable and efficient. Now in-vivo microscopy can be performed using confocal laser endomicroscopy, optical coherence tomography, spectroscopy, etc. Besides developments in diagnostic colonoscopy, therapeutic colonoscopy has improved to manage lower gastrointestinal tract bleeding, obstruction, perforations, resection polyps, and early colorectal cancers. The introduction of combined endo-laparoscopic surgery and robotic endoscopic surgery has made these interventions feasible. The role of artificial intelligence in the diagnosis and management of colorectal diseases is also increasing day by day. Hence, this article is to review cutting-edge developments in endoscopic principles for the management of colorectal diseases.
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Affiliation(s)
- Nalini Kanta Ghosh
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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17
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Smith HG, Schlesinger NH, Krarup PM, Nordholm-Carstensen A. Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study. Colorectal Dis 2024; 26:1175-1183. [PMID: 38807258 DOI: 10.1111/codi.17049] [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: 11/11/2023] [Revised: 02/28/2024] [Accepted: 05/05/2024] [Indexed: 05/30/2024]
Abstract
AIM Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. METHOD This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. RESULTS A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. CONCLUSION LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.
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Affiliation(s)
- Henry G Smith
- Abdominalcenter K, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Nis H Schlesinger
- Abdominalcenter K, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Peter-Martin Krarup
- Abdominalcenter K, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
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18
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Smith HG, Nilsson PJ, Shogan BD, Harji D, Gambacorta MA, Romano A, Brandl A, Qvortrup C. Neoadjuvant treatment of colorectal cancer: comprehensive review. BJS Open 2024; 8:zrae038. [PMID: 38747103 PMCID: PMC11094476 DOI: 10.1093/bjsopen/zrae038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 03/12/2024] [Accepted: 03/21/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. METHODS A narrative review of the most recent relevant literature was conducted. RESULTS Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. CONCLUSION Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.
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Affiliation(s)
- Henry G Smith
- Abdominalcenter K, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Per J Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Dept. of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Benjamin D Shogan
- Department of Surgery, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Deena Harji
- Department of Colorectal Surgery, Manchester University NHS Foundation Trust, Manchester, UK
| | - Maria Antonietta Gambacorta
- Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
- Dipartimento di Scienze Radiologiche ed Ematologiche, Universita Cattolica del Sacro Cuore, Rome, Italy
| | - Angela Romano
- Dipartimento di Diagnostica per Immagini, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
| | - Andreas Brandl
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Camilla Qvortrup
- Department of Oncology, Rigshospital, University of Copenhagen, Copenhagen, Denmark
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19
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Ma Y, Ma D, Xu X, Li J, Guan Z. Progress of MRI in predicting the circumferential resection margin of rectal cancer: A narrative review. Asian J Surg 2024; 47:2122-2131. [PMID: 38331609 DOI: 10.1016/j.asjsur.2024.01.131] [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: 10/27/2023] [Revised: 01/02/2024] [Accepted: 01/19/2024] [Indexed: 02/10/2024] Open
Abstract
Rectal cancer (RC) is the third most frequently diagnosed cancer worldwide, and the status of its circumferential resection margin (CRM) is of paramount significance for treatment strategies and prognosis. CRM involvement is defined as tumor touching or within 1 mm from the outermost part of tumor or outer border of the mesorectal or lymph node deposits to the resection margin. The incidence of involved CRM varied from 5.4 % to 36 %, which may associate with an in consistent definition of CRM, the quality of surgeries, and the different examination modalities. Although T and N status are essential factors in determining whether a patient should receive neoadjuvant therapy before surgery, CRM status is a powerful predictor of local and distant recurrence as well as survival rate. This review explores the significance of CRM, the various assessment methods, and the role of magnetic resonance imaging (MRI) and artificial intelligence-based MRI in predicting CRM status. MRI showed potential advantage in predicting CRM status with a high sensitivity and specificity compared to computed tomography (CT). We also discuss MRI advancements in RC imaging, including conventional MRI with body coil, high-resolution MRI with phased-array coil, and endorectal MRI. Along with a discussion of artificial intelligence-based MRI techniques to predict the CRM status of RCs before and after treatments.
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Affiliation(s)
- Yanqing Ma
- Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
| | - Dongnan Ma
- Yangming College of Ningbo University, Ningbo, Zhejiang, 315010, China.
| | - Xiren Xu
- Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
| | - Jie Li
- Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
| | - Zheng Guan
- Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
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20
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Valentini V, Alfieri S, Coco C, D'Ugo D, Crucitti A, Pacelli F, Persiani R, Sofo L, Picciocchi A, Doglietto GB, Barbaro B, Vecchio FM, Ricci R, Damiani A, Savino MC, Boldrini L, Cellini F, Meldolesi E, Romano A, Chiloiro G, Gambacorta MA. Four steps in the evolution of rectal cancer managements through 40 years of clinical practice: Pioneering, standardization, challenges and personalization. Radiother Oncol 2024; 194:110190. [PMID: 38438019 DOI: 10.1016/j.radonc.2024.110190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 02/26/2024] [Indexed: 03/06/2024]
Affiliation(s)
- Vincenzo Valentini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Sergio Alfieri
- Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Claudio Coco
- U.O.C. Chirurgia Generale 2, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Domenico D'Ugo
- Unità di chirurgia generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Fabio Pacelli
- Unità chirurgica del peritoneo e del retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Persiani
- Unità di chirurgia generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Luigi Sofo
- Divisione di Chirurgia Addominale, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Aurelio Picciocchi
- Dipartimento di Chirurgia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giovanni Battista Doglietto
- Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Brunella Barbaro
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Fabio Maria Vecchio
- Dipartimento di Patologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Riccardo Ricci
- Dipartimento di Patologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Andrea Damiani
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Chiara Savino
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Luca Boldrini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Cellini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Elisa Meldolesi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Angela Romano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giuditta Chiloiro
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
| | - Maria Antonietta Gambacorta
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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21
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Temmink SJD, Peeters KCMJ, Nilsson PJ, Martling A, van de Velde CJH. Surgical Outcomes after Radiotherapy in Rectal Cancer. Cancers (Basel) 2024; 16:1539. [PMID: 38672621 PMCID: PMC11048284 DOI: 10.3390/cancers16081539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/12/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.
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Affiliation(s)
- Sofieke J. D. Temmink
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Koen C. M. J. Peeters
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Per J. Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
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22
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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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23
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Loria A, Ramsdale EE, Aquina CT, Cupertino P, Mohile SG, Fleming FJ. From Clinical Trials to Practice: Anticipating and Overcoming Challenges in Implementing Watch-and-Wait for Rectal Cancer. J Clin Oncol 2024; 42:876-880. [PMID: 38315943 DOI: 10.1200/jco.23.01369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 11/10/2023] [Accepted: 12/12/2023] [Indexed: 02/07/2024] Open
Affiliation(s)
- Anthony Loria
- Department of Surgery, University of Rochester Medical Center, Rochester, NY
| | - Erika E Ramsdale
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY
| | - Christopher T Aquina
- Departments of Colorectal Surgery and Surgical Oncology, AdventHealth Orlando, Orlando, FL
| | - Paula Cupertino
- Department of Surgery, University of Rochester Medical Center, Rochester, NY
| | - Supriya G Mohile
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY
| | - Fergal J Fleming
- Department of Surgery, University of Rochester Medical Center, Rochester, NY
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY
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Duggan WP, Heagney N, Gray S, Hannan E, Burke JP. Transanal minimally invasive surgery (TAMIS) for local excision of benign and malignant rectal neoplasia: a 7-year experience. Langenbecks Arch Surg 2024; 409:32. [PMID: 38191937 PMCID: PMC10774178 DOI: 10.1007/s00423-023-03217-4] [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] [Received: 08/02/2023] [Accepted: 12/29/2023] [Indexed: 01/10/2024]
Abstract
PURPOSE Transanal minimally invasive surgery (TAMIS) is an advanced transanal platform that can be utilised to perform high-quality local excision (LE) of rectal neoplasia. This study describes clinical and midterm oncological outcomes from a single unit's 7-year experience with TAMIS. METHODS Consecutive patients who underwent TAMIS LE at our institution between January 1st, 2016, and December 31st, 2022, were identified from a prospectively maintained database. Indication for TAMIS LE was benign lesions not amenable to endoscopic excision or histologically favourable early rectal cancers. The primary endpoints were resection quality, disease recurrence and peri-operative outcomes. The Kaplan-Meier survival analyses were used to describe disease-free survival (DFS) for patients with rectal adenocarcinoma that did not receive immediate salvage proctectomy. RESULTS There were 168 elective TAMIS LE procedures performed for 102 benign and 66 malignant lesions. Overall, a 95.2% negative margin rate was observed, and 96.4% of lesions were submitted without fragmentation. Post-operative morbidity was recorded in 8.3% of patients, with post-operative haemorrhage, being the most common complication encountered. The mean follow-up was 17 months (SD 15). Local recurrence occurred in 1.6%, and distant organ metastasis was noted in 1.6% of patients. CONCLUSIONS For carefully selected patients, TAMIS for local excision of early rectal neoplasia is a valid option with low morbidity that maintains the advantages of organ preservation.
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Affiliation(s)
- William P Duggan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Niall Heagney
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Sean Gray
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Enda Hannan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
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25
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Sijmons JML, Dekker JWT, Tuynman JB, Mohan HM, Smart P, Heriot AG, Walker K, Kuryba A, Matthiessen P, Tanis PJ. Evolution of surgical approach to rectal cancer resection: A multinational registry assessment. Int J Colorectal Dis 2024; 39:15. [PMID: 38183451 DOI: 10.1007/s00384-023-04578-4] [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: 12/06/2023] [Indexed: 01/08/2024]
Abstract
PURPOSE Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. METHODS Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). RESULTS Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5-9.0%). The MIS proportion was highly variable between countries in the period 2010-2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015-2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. CONCLUSIONS Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time.
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Affiliation(s)
| | | | | | - Helen M Mohan
- Bowel Cancer Outcomes Registry (BCOR), Melbourne, Australia
| | - Philip Smart
- Bowel Cancer Outcomes Registry (BCOR), Melbourne, Australia
| | | | - Kate Walker
- National Bowel Cancer Audit (NBOCA), Leeds, UK
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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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Smits LJH, van Lieshout AS, Debets S, Spoor S, Moons LMG, Peeters KCMJ, van Oostendorp SE, Damman OC, Janssens RJPA, Lameris W, van Grieken NCT, Tuynman JB. Patients' perspectives and the perceptions of healthcare providers in the treatment of early rectal cancer; a qualitative study. BMC Cancer 2023; 23:1266. [PMID: 38129790 PMCID: PMC10740344 DOI: 10.1186/s12885-023-11734-0] [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: 06/20/2023] [Accepted: 12/08/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Shared decision-making has become of increased importance in choosing the most suitable treatment strategy for early rectal cancer, however, clinical decision-making is still primarily based on physicians' perspectives. Balancing quality of life and oncological outcomes is difficult, and guidance on patients' involvement in this subject in early rectal cancer is limited. Therefore, this study aimed to explore preferences and priorities of patients as well as physicians' perspectives in treatment for early rectal cancer. METHODS In this qualitative study, semi-structured interviews were performed with early rectal cancer patients (n = 10) and healthcare providers (n = 10). Participants were asked which factors influenced their preferences and how important these factors were. Thematic analyses were performed. In addition, participants were asked to rank the discussed factors according to importance to gain additional insights. RESULTS Patients addressed the following relevant factors: the risk of an ostomy, risk of poor bowel function and treatment related complications. Healthcare providers emphasized oncological outcomes as tumour recurrence, risk of an ostomy and poor bowel function. Patients perceived absolute risks of adverse outcome to be lower than healthcare providers and were quite willing undergo organ preservation to achieve a better prospect of quality of life. CONCLUSION Patients' preferences in treatment of early rectal cancer vary between patients and frequently differ from assumptions of preferences by healthcare providers. To optimize future shared decision-making, healthcare providers should be aware of these differences and should invite patients to explore and address their priorities more explicitly during consultation. Factors deemed important by both physicians and patients should be expressed during consultation to decide on a tailored treatment strategy.
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Affiliation(s)
- Lisanne J H Smits
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands.
| | - Annabel S van Lieshout
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands
| | - Saskia Debets
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands
| | - Sacha Spoor
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands
| | - Leon M G Moons
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Koen C M J Peeters
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | | | - Olga C Damman
- Department of Public and Occupational Health, Vrije Universiteit Amsterdam, Public Health Research Institute, Amsterdam, the Netherlands
| | | | - Wytze Lameris
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands
| | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, the Netherlands
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Chen Y, Wang Y, Zhang H, Wan J, Shen L, Wang Y, Zhou M, Wu R, Yang W, Zhou S, Cai S, Li X, Zhang Z, Xia F. Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E). BMJ Open 2023; 13:e076048. [PMID: 37802608 PMCID: PMC10565143 DOI: 10.1136/bmjopen-2023-076048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 09/19/2023] [Indexed: 10/10/2023] Open
Abstract
INTRODUCTION Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a 'Watch & Wait' (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer. METHODS AND ANALYSIS TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3-4 adverse effects rate and patients' quality of life. ETHICS AND DISSEMINATION This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER NCT05555888 (ClinicalTrials.gov).
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Affiliation(s)
- Yajie Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Yaqi Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Hui Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Juefeng Wan
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Lijun Shen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Yan Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Menglong Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Ruiyan Wu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Wang Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shujuan Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Sanjun Cai
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xinxiang Li
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhen Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Fan Xia
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China
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El Khababi N, Beets-Tan RGH, Tissier R, Lahaye MJ, Maas M, Curvo-Semedo L, Dresen RC, Nougaret S, Beets GL, Lambregts DMJ. Predicting response to chemoradiotherapy in rectal cancer via visual morphologic assessment and staging on baseline MRI: a multicenter and multireader study. Abdom Radiol (NY) 2023; 48:3039-3049. [PMID: 37358604 PMCID: PMC10480283 DOI: 10.1007/s00261-023-03961-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/11/2023] [Accepted: 05/13/2023] [Indexed: 06/27/2023]
Abstract
PURPOSE Pre-treatment knowledge of the anticipated response of rectal tumors to neoadjuvant chemoradiotherapy (CRT) could help to further optimize the treatment. Van Griethuysen et al. proposed a visual 5-point confidence score to predict the likelihood of response on baseline MRI. Aim was to evaluate this score in a multicenter and multireader study setting and compare it to two simplified (4-point and 2-point) adaptations in terms of diagnostic performance, interobserver agreement (IOA), and reader preference. METHODS Twenty-two radiologists from 14 countries (5 MRI-experts,17 general/abdominal radiologists) retrospectively reviewed 90 baseline MRIs to estimate if patients would likely achieve a (near-)complete response (nCR); first using the 5-point score by van Griethuysen (1=highly unlikely to 5=highly likely to achieve nCR), second using a 4-point adaptation (with 1-point each for high-risk T-stage, obvious mesorectal fascia invasion, nodal involvement, and extramural vascular invasion), and third using a 2-point score (unlikely/likely to achieve nCR). Diagnostic performance was calculated using ROC curves and IOA using Krippendorf's alpha (α). RESULTS Areas under the ROC curve to predict the likelihood of a nCR were similar for the three methods (0.71-0.74). IOA was higher for the 5- and 4-point scores (α=0.55 and 0.57 versus 0.46 for the 2-point score) with best results for the MRI-experts (α=0.64-0.65). Most readers (55%) favored the 4-point score. CONCLUSIONS Visual morphologic assessment and staging methods can predict neoadjuvant treatment response with moderate-good performance. Compared to a previously published confidence-based scoring system, study readers preferred a simplified 4-point risk score based on high-risk T-stage, MRF involvement, nodal involvement, and EMVI.
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Affiliation(s)
- Najim El Khababi
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Regina G H Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Renaud Tissier
- Biostatistics Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Max J Lahaye
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Monique Maas
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Luís Curvo-Semedo
- Department of Radiology, Faculty of Medicine, Centro Hospitalar e Universitario de Coimbra EPE, University of Coimbra, Coimbra, Portugal
| | - Raphaëla C Dresen
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Stephanie Nougaret
- Medical Imaging Department, Montpellier Cancer Institute, Montpellier Cancer Research Institute (U1194), University of Montpellier, Montpellier, France
| | - Geerard L Beets
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Doenja M J Lambregts
- Department of Radiology, The Netherlands Cancer Institute, P.O. Box 90203, 1106 BE, Amsterdam, The Netherlands.
- GROW School for Oncology & Developmental Biology, University of Maastricht, Maastricht, The Netherlands.
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30
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Tanaka MD, Geubels BM, Grotenhuis BA, Marijnen CAM, Peters FP, van der Mierden S, Maas M, Couwenberg AM. Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal. Cancers (Basel) 2023; 15:3945. [PMID: 37568760 PMCID: PMC10417363 DOI: 10.3390/cancers15153945] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/27/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might improve predictive accuracy. The aim of this systematic review was to summarize and critically appraise validated pretreatment prediction models (other than radiomics-based models or image-based deep learning models) for response to neoadjuvant therapy in patients with rectal cancer and provide evidence-based recommendations for future research. MEDLINE via Ovid, Embase.com, and Scopus were searched for eligible studies published up to November 2022. A total of 5006 studies were screened and 16 were included for data extraction and risk of bias assessment using Prediction model Risk Of Bias Assessment Tool (PROBAST). All selected models were unique and grouped into five predictor categories: clinical, combined, genetics, metabolites, and pathology. Studies generally included patients with intermediate or advanced tumor stages who were treated with neoadjuvant chemoradiotherapy. Evaluated outcomes were pathological complete response and pathological tumor response. All studies were considered to have a high risk of bias and none of the models were externally validated in an independent study. Discriminative performances, estimated with the area under the curve (AUC), ranged per predictor category from 0.60 to 0.70 (clinical), 0.78 to 0.81 (combined), 0.66 to 0.91 (genetics), 0.54 to 0.80 (metabolites), and 0.71 to 0.91 (pathology). Model calibration outcomes were reported in five studies. Two collagen feature-based models showed the best predictive performance (AUCs 0.83-0.91 and good calibration). In conclusion, some pretreatment models for response prediction in rectal cancer show encouraging predictive potential but, given the high risk of bias in these studies, their value should be evaluated in future, well-designed studies.
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Affiliation(s)
- Max D. Tanaka
- Department of Radiation Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
| | - Barbara M. Geubels
- Department of Surgery, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
- Department of Surgery, Catharina Hospital, 5602 ZA Eindhoven, The Netherlands
- GROW School for Oncology and Reproduction, Maastricht University, 6200 MD Maastricht, The Netherlands
| | - Brechtje A. Grotenhuis
- Department of Surgery, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
| | - Corrie A. M. Marijnen
- Department of Radiation Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
- Department of Radiation Oncology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands
| | - Femke P. Peters
- Department of Radiation Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
| | - Stevie van der Mierden
- Scientific Information Service, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
| | - Monique Maas
- GROW School for Oncology and Reproduction, Maastricht University, 6200 MD Maastricht, The Netherlands
- Department of Radiology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
| | - Alice M. Couwenberg
- Department of Radiation Oncology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
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Hofste LSM, Geerlings MJ, von Rhein D, Rütten H, Westenberg AH, Weiss MM, Gilissen C, Hofste T, van der Post RS, Klarenbeek BR, de Wilt JHW, Ligtenberg MJL. Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1283-1290. [PMID: 36740555 DOI: 10.1016/j.ejso.2023.01.026] [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: 11/03/2022] [Revised: 12/30/2022] [Accepted: 01/24/2023] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. MATERIALS AND METHODS Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. RESULTS Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). CONCLUSION These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.
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Affiliation(s)
- Lisa S M Hofste
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Maartje J Geerlings
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Daniel von Rhein
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Heidi Rütten
- Department of Radiation Oncology, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - A Helen Westenberg
- Institute for Radiation Oncology Arnhem, 6815, AD, Arnhem, the Netherlands
| | - Marjan M Weiss
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Christian Gilissen
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Tom Hofste
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Bastiaan R Klarenbeek
- Department of Surgery, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands
| | - Marjolijn J L Ligtenberg
- Department of Human Genetics, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands; Department of Pathology, Radboud University Medical Center, 6525, GA, Nijmegen, the Netherlands.
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Rooney MK, De B, Corrigan K, Smith GL, Taniguchi C, Minsky BD, Ludmir EB, Koay EJ, Das P, Koong AC, Peacock O, Chang G, You YN, Morris VK, Nogueras-González G, Holliday EB. Patient-reported Bowel Function and Bowel-related Quality of Life After Pelvic Radiation for Rectal Adenocarcinoma: The Impact of Radiation Fractionation and Surgical Resection. Clin Colorectal Cancer 2023; 22:211-221. [PMID: 36878805 PMCID: PMC10213111 DOI: 10.1016/j.clcc.2023.02.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 02/10/2023] [Indexed: 02/17/2023]
Abstract
INTRODUCTION Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited. METHODS Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management. RESULTS Of 204 patients surveyed, 124 (60.8%) responded. Median (interquartile range) time from radiation to survey completion was 30.1 (18.3-43) months. Seventy-nine (63.7%) respondents received LCRT, and 45 (36.3%) received SCRT; 101 (81.5%) respondents underwent surgery, and 23 (18.5%) pursued nonoperative management. There were no differences in LARS, FIQoL or FACT-G7 between patients receiving LCRT versus SCRT. On multivariable analysis, only nonoperative management was associated with lower LARS score signifying less bowel dysfunction. Nonoperative management and female sex were associated with a higher FIQoL score signifying less disruption and distress from fecal incontinence issues. Finally, lower BMI at the time of radiation, female sex, and higher FIQoL score were associated with higher FACT-G7 scores signifying better overall QOL. CONCLUSIONS These results suggest long-term patient-reported bowel function and QOL may be similar for individuals receiving SCRT and LCRT for the treatment of LARC, but nonoperative management may lead to improved bowel function and QOL.
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Affiliation(s)
- Michael K Rooney
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brian De
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kelsey Corrigan
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Grace L Smith
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Cullen Taniguchi
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bruce D Minsky
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ethan B Ludmir
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eugene J Koay
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Albert C Koong
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Oliver Peacock
- Department of Colorectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - George Chang
- Department of Colorectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Y Nancy You
- Department of Colorectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | - Emma B Holliday
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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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: 25] [Impact Index Per Article: 12.5] [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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34
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de Wilt JHW, Bach SP. Is it time for a paradigm shift in early rectal cancer treatment? Ann Oncol 2023; 34:336-338. [PMID: 36646319 DOI: 10.1016/j.annonc.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/15/2023] Open
Affiliation(s)
- J H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - S P Bach
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
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35
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Li J, Ma Y, Wen L, Zhang G, Yao X. Outcomes after the watch-and-wait strategy and local excision treatment for rectal cancer: a meta-analysis. Expert Rev Anticancer Ther 2023; 23:555-564. [PMID: 36795784 DOI: 10.1080/14737140.2023.2181796] [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: 02/17/2023]
Abstract
BACKGROUND The watch-and-wait (W&W) strategy and local excision (LE) have been used in patients with clinical complete response (cCR) for rectal cancer, but the comparative outcomes of the two strategies are controversial. We compared the efficacy of the W&W strategy with LE for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) or total neoadjuvant therapy (TNT). RESEARCH DESIGN AND METHODS Several domestic and foreign databases were searched for the relevant literature on comparative trials of the W&W strategy and LE surgery for rectal cancer after neoadjuvant therapy with the following outcomes; differences in local recurrence (LR), distant metastasis (DM/DM+LR), 3-year disease-free survival (DFS), 3-year local recurrence-free survival (LRFS) and 3-year overall survival (OS). RESULTS Nine articles, were analyzed. Overall, 442 patients were included, with 267 and 175 patients in the W&W and LE groups, respectively. Meta-analysis results showed no significant differences the between W&W and LE groups with respect to LR, DM/DM+LR, 3-year DFS, 3-year LRFS, and 3-year OS. This study has been registered in PROSPERO (registration number: CRD42022331208). CONCLUSION The W&W strategy may be preferred for some rectal cancer patients who select LE and reach cCR or near cCR after nCRT or TNT.
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Affiliation(s)
- Jinghui Li
- Gannan Medical university, Ganzhou, Jiangxi, China.,Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.,Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, PR, China
| | - Yongli Ma
- Gannan Medical university, Ganzhou, Jiangxi, China.,Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China
| | - Liang Wen
- Gannan Medical university, Ganzhou, Jiangxi, China.,Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.,Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, PR, China
| | - Guosheng Zhang
- Gannan Medical university, Ganzhou, Jiangxi, China.,Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China
| | - Xueqing Yao
- Gannan Medical university, Ganzhou, Jiangxi, China.,Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.,Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, PR, China
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36
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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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37
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Assessment of Quality of Life in Rectal Cancer with Organ-Preservation Treatment: Are We There yet? Clin Oncol (R Coll Radiol) 2023; 35:e110-e120. [PMID: 36443138 DOI: 10.1016/j.clon.2022.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/14/2022] [Accepted: 11/02/2022] [Indexed: 11/27/2022]
Abstract
Rectal cancer is a common cancer and shows an increased incidence with older age. Although the gold standard treatment is surgical excision, minimally invasive approaches are increasingly used and organ preservation is becoming a reasonable approach. The conservative treatment approach includes local excision, external beam radiotherapy and brachytherapy. However, these all carry a risk of side-effects. It is crucial to provide patients with information to quantify the improvement or detriment in quality of life with their cancer treatment. This can only be done with patient-reported outcome measures (PROMs) as tools within current and future trials. Colorectal cancer has numerous publications with specific PROMs. However, PROMs reporting in rectal cancer is more sparse; PROMs are generally extrapolated from colorectal cancer. Rectal PROMs trials hold small population samples and PROMs as an end point is scarce. We present a review of recent literature based on the PROMs reporting of quality of life for rectal cancer patients and introduce the CITRuS trial as an innovative feasibility study related to electronic PROMs data collection.
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38
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Bach SP. STAR-TREC: An International Three-arm Multicentre, Partially Randomised Controlled Trial Incorporating an External Pilot. Clin Oncol (R Coll Radiol) 2023; 35:e107-e109. [PMID: 36577551 DOI: 10.1016/j.clon.2022.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/08/2022] [Accepted: 12/12/2022] [Indexed: 12/27/2022]
Abstract
AIM Organ saving treatment for early-stage rectal cancer can reduce patient reported side effects compared to standard total mesorectal excision (TME) and preserve quality of life (QOL). An optimal strategy for achieving organ preservation and longer-term oncological outcomes are unknown, thus there is a need for high quality trials. METHOD Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC) is an international 3-arm multi-centre, partially randomised controlled trial incorporating an external pilot. In phase III, patients with cT1-3b N0 tumours, ≤40mm in diameter, who prefer organ preservation are randomised 1:1 between mesorectal long course chemoradiation versus mesorectal short course radiotherapy, with selective transanal microsurgery. Patients preferring radical surgery receive TME. STAR-TREC aims to recruit 380 patients to organ preservation and 120 to TME surgery. The primary outcome is the rate of organ preservation at 30 months. Secondary clinician reported outcomes include acute treatment-related toxicity, rate of non-operative management, non-regrowth pelvic tumour control at 36 months, non-regrowth disease free survival at 36 months, and overall survival at 60 months and patient reported toxicity, health related QOL at baseline, 12 and 24 months. Exploratory biomarker research uses circulating tumour DNA to predict response and relapse. DISCUSSION STAR-TREC will prospectively evaluate contrasting therapeutic strategies and implement new measures including a smaller mesorectal target volume, 2-step response assessment and non-operative management for complete response. The trial will yield important information to guide routine management of patients with early-stage rectal cancer.
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Affiliation(s)
- S P Bach
- Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
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39
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Development of a Patient Decision Aid for Rectal Cancer Patients with Clinical Complete Response after Neo-Adjuvant Treatment. Cancers (Basel) 2023; 15:cancers15030806. [PMID: 36765766 PMCID: PMC9913303 DOI: 10.3390/cancers15030806] [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: 11/19/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 02/01/2023] Open
Abstract
Surgery is the primary component of curative treatment for patients with rectal cancer. However, patients with a clinical complete response (cCR) after neo-adjuvant treatment may avoid the morbidity and mortality of radical surgery. An organ-sparing strategy could be an oncological equivalent alternative. Therefore, shared decision making between the patient and the healthcare professional (HCP) should take place. This can be facilitated by a patient decision aid (PtDA). In this study, we developed a PtDA based on a literature review and the key elements of the Ottawa Decision Support Framework. Additionally, a qualitative study was performed to review and evaluate the PtDA by both HCPs and former rectal cancer patients by a Delphi procedure and semi-structured interviews, respectively. A strong consensus was reached after the first round (I-CVI 0.85-1). Eleven patients were interviewed and most of them indicated that using a PtDA in clinical practice would be of added value in the decision making. Patients indicated that their decisional needs are centered on the impact of side effects on their quality of life and the outcome of the different options. The PtDA was modified taking into account the remarks of patients and HCPs and a second Delphi round was held. The second round again showed a strong consensus (I-CVI 0.87-1).
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40
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Gilbert A, Homer V, Brock K, Korsgen S, Geh I, Hill J, Gill T, Hainsworth P, Tutton M, Khan J, Robinson J, Steward M, Cunningham C, Kaur M, Magill L, Russell A, Quirke P, West NP, Sebag-Montefiore D, Bach SP. Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision. THE LANCET. HEALTHY LONGEVITY 2022; 3:e825-e838. [PMID: 36403589 PMCID: PMC9722406 DOI: 10.1016/s2666-7568(22)00239-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 09/15/2022] [Accepted: 09/20/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1-2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84-99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. METHODS Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. FINDINGS Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67-80] vs 65 years [61-71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6-12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. INTERPRETATION The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. FUNDING Cancer Research UK.
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Affiliation(s)
- Alexandra Gilbert
- Leeds Institute for Medical Research, University of Leeds, Leeds, UK.
| | - Victoria Homer
- Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Kristian Brock
- Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Stephan Korsgen
- Department of Colorectal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Ian Geh
- Department of Radiation Oncology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - James Hill
- Department of Colorectal Surgery, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Talvinder Gill
- Department of Colorectal Surgery, North Tees and Hartlepool NHS Foundation Trust, Durham, UK
| | - Paul Hainsworth
- Department of Colorectal Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Matthew Tutton
- Department of Colorectal Surgery, East Suffolk and North Essex NHS Foundation Trust, Colchester, UK
| | - Jim Khan
- Department of Colorectal Surgery, Portsmouth Hospital NHS Trust, Portsmouth, UK
| | - Jonathan Robinson
- Department of Colorectal Surgery, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Mark Steward
- Department of Colorectal Surgery, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Christopher Cunningham
- Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Manjinder Kaur
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Laura Magill
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Ann Russell
- National Cancer Research Institute, London, UK
| | - Philip Quirke
- Division of Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, UK
| | - Nicholas P West
- Division of Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, UK
| | | | - Simon P Bach
- Department of Colorectal Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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41
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Wanigasooriya K, Barros-Silva JD, Tee L, El-asrag ME, Stodolna A, Pickles OJ, Stockton J, Bryer C, Hoare R, Whalley CM, Tyler R, Sillo T, Yau C, Ismail T, Beggs AD. Patient Derived Organoids Confirm That PI3K/AKT Signalling Is an Escape Pathway for Radioresistance and a Target for Therapy in Rectal Cancer. Front Oncol 2022; 12:920444. [PMID: 35860583 PMCID: PMC9289101 DOI: 10.3389/fonc.2022.920444] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models. Design To understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens. Results RNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected (p=0.027) which was abrogated with dual PI3K/mTOR inhibitors and lead to significant radiosensitisation of the HCT116 cell line and radiation resistant PDO lines. Conclusions The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.
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Affiliation(s)
- Kasun Wanigasooriya
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Joao D. Barros-Silva
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Louise Tee
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Mohammed E. El-asrag
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Agata Stodolna
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Oliver J. Pickles
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Joanne Stockton
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Claire Bryer
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Rachel Hoare
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Celina M. Whalley
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Robert Tyler
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Toritseju Sillo
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Christopher Yau
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
| | - Tariq Ismail
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Andrew D. Beggs
- Institute of Cancer and Genomic Science, College of Medical and Dental Science, University of Birmingham, Birmingham, United Kingdom
- Department of Surgery, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
- *Correspondence: Andrew D. Beggs,
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