{"entity":{"id":"idea-crc-organ-preservation-randomised-in-pmmr-rectal","kind":"idea","name":"Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint","aka":[],"tldr":"Half of rectal cancer patients given all their chemotherapy and radiotherapy first can keep their rectum. Nobody has ever randomised that against having the operation, so the trade-off between avoiding a stoma and the risk of the cancer regrowing is still guesswork.","summary":"Habr-Gama watched 71 of 265 patients whose rectal cancers vanished after chemoradiotherapy and reported ten-year overall survival of 97.7 percent across the series; OPRA made the strategy plannable, with three-year survival free of total mesorectal excision of 53 percent after consolidation chemotherapy and disease-free survival matching the 75 percent historical rate. In mismatch repair-deficient disease the question has been answered emphatically: every one of 49 rectal cancers treated with six months of dostarlimab had a clinical complete response, 82 of 103 patients across both Cercek cohorts avoided surgery, and two-year recurrence-free survival was 92 percent.\n\nFor the mismatch repair-proficient 90 percent, the evidence remains single-arm or historically controlled. OPRA's comparison is against historical data; regrowth continues beyond three years; and the assumption that salvage surgery after regrowth costs nothing rests on subgroup comparisons within the same non-randomised cohort. Meanwhile the thing patients actually weigh, long-term bowel, urinary and sexual function after watch and wait against after total mesorectal excision, has never been a primary endpoint.","asOf":"2026-09-24","links":[{"label":"Garcia-Aguilar et al.: OPRA (J Clin Oncol 2022)","url":"https://europepmc.org/article/MED/35483010"},{"label":"Cercek et al.: nonoperative management of mismatch repair-deficient tumours (N Engl J Med 2025)","url":"https://europepmc.org/article/MED/40293177"},{"label":"ClinicalTrials.gov NCT05610163","url":"https://clinicaltrials.gov/study/NCT05610163"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","surgery-roadmap"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery","radiation"],"technologies":["radiotherapy","mri","imrt-igrt","robotic-surgery"],"targets":[],"drugs":["folfox","capox","capecitabine","dostarlimab"],"companies":[],"institutions":[],"pathways":[],"terms":["organ-preservation","clinical-complete-response","total-neoadjuvant-therapy","total-mesorectal-excision"],"trials":["opra","rapido","prodige-23","azur-1"],"people":["julio-garcia-aguilar","andrea-cercek","angelita-habr-gama"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-trial-design"],"keyPapers":["paper-garcia-aguilar-opra-organ-preservation-jco-2022","paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In mismatch repair-proficient locally advanced rectal cancer with a clinical complete response after total neoadjuvant therapy, watch and wait is non-inferior to immediate total mesorectal excision for five-year disease-free survival and superior for patient-reported bowel function at two years.","rationale":"Organ preservation is already offered outside trials on the strength of OPRA and the international watch-and-wait registry, so the randomised comparison is becoming harder to run each year; and the function benefit that justifies the strategy has never been measured against the comparator it replaces.","test":"A randomised non-inferiority trial in patients with a clinical complete response after total neoadjuvant therapy, stratified by response assessment method, with five-year disease-free survival and two-year patient-reported bowel function as co-primary endpoints, MRI and endoscopic restaging centrally reviewed, and stoma-free survival, local regrowth and salvage resection rates reported as secondary outcomes. JANUS and the running total neoadjuvant therapy trials supply the platform.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":6},"route":"/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"surgery-roadmap","kind":"roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"section":[{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"},{"id":"surgery","kind":"section","name":"Surgery & Interventional","route":"/fronts/surgery/"}],"term":[{"id":"clinical-complete-response","kind":"term","name":"Clinical complete response (cCR)","route":"/terms/clinical-complete-response/"},{"id":"organ-preservation","kind":"term","name":"Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)","route":"/terms/organ-preservation/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"},{"id":"total-mesorectal-excision","kind":"term","name":"Total mesorectal excision (TME)","route":"/terms/total-mesorectal-excision/"},{"id":"total-neoadjuvant-therapy","kind":"term","name":"Total neoadjuvant therapy (TNT, rectal cancer)","route":"/terms/total-neoadjuvant-therapy/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"}],"trial":[{"id":"azur-1","kind":"trial","name":"AZUR-1","route":"/trials/azur-1/"},{"id":"opra","kind":"trial","name":"OPRA","route":"/trials/opra/"},{"id":"prodige-23","kind":"trial","name":"PRODIGE 23","route":"/trials/prodige-23/"},{"id":"rapido","kind":"trial","name":"RAPIDO","route":"/trials/rapido/"}],"person":[{"id":"andrea-cercek","kind":"person","name":"Andrea Cercek","route":"/people/andrea-cercek/"},{"id":"angelita-habr-gama","kind":"person","name":"Angelita Habr-Gama","route":"/people/angelita-habr-gama/"},{"id":"julio-garcia-aguilar","kind":"person","name":"Julio Garcia-Aguilar","route":"/people/julio-garcia-aguilar/"}],"bottleneck":[{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","kind":"paper","name":"Nonoperative management of mismatch repair-deficient tumors","route":"/key-papers/paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025/"},{"id":"paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","kind":"paper","name":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results","route":"/key-papers/paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004/"},{"id":"paper-garcia-aguilar-opra-organ-preservation-jco-2022","kind":"paper","name":"Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA)","route":"/key-papers/paper-garcia-aguilar-opra-organ-preservation-jco-2022/"},{"id":"paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021","kind":"paper","name":"Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)","route":"/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/"}]}}