{"entity":{"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)","aka":[],"tldr":"Planning for watch and wait from the start, rather than stumbling into it, let half of 324 rectal cancer patients keep their rectum with no loss of disease-free survival.","summary":"Garcia-Aguilar, Patil, Gollub and colleagues randomised 324 patients with stage II or III rectal adenocarcinoma to induction chemotherapy followed by chemoradiotherapy, or chemoradiotherapy followed by consolidation chemotherapy, and then to total mesorectal excision or watch and wait on the basis of tumour response. Both groups received four months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation with concurrent fluorouracil or capecitabine. The trial was designed as two stand-alone studies with disease-free survival as the primary endpoint for each, compared against a null hypothesis based on historical data; the secondary endpoint was survival free of total mesorectal excision.\n\nPatients who underwent total mesorectal excision after restaging and those who underwent it after regrowth had similar disease-free survival, which is the finding that makes a trial of watch and wait ethically defensible.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00032"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35483010/"},{"label":"Europe PMC full text (PMC9362876)","url":"https://europepmc.org/article/MED/35483010"}],"tags":["colorectal-evidence"],"related":["paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery","radiation"],"technologies":["radiotherapy","mri"],"targets":[],"drugs":["folfox","capox","capecitabine","fluorouracil"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["organ-preservation","clinical-complete-response","total-neoadjuvant-therapy","total-mesorectal-excision"],"trials":["opra"],"people":["julio-garcia-aguilar","andrea-cercek"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00032","pmid":"35483010","authors":"Garcia-Aguilar J, Patil S, Gollub MJ, et al.","paperType":"rct","findings":["Three-year disease-free survival 76 percent (95 percent CI 69 to 84) after induction chemotherapy then chemoradiotherapy and 76 percent (69 to 83) after chemoradiotherapy then consolidation chemotherapy, matching the 75 percent historical rate.","Three-year survival free of total mesorectal excision 41 percent (33 to 50) and 53 percent (45 to 62) respectively.","No differences between groups in local recurrence-free, distant metastasis-free or overall survival.","Disease-free survival was similar whether total mesorectal excision followed restaging or followed regrowth."],"whatItMeans":"Organ preservation became a plan rather than an accident: consolidation chemotherapy after chemoradiotherapy gives the best chance of keeping the rectum, and salvage surgery after regrowth does not appear to cost survival.","caveats":["The disease-free survival comparison is against historical controls, not a randomised surgical arm.","Median follow-up three years; regrowth continues after that and the durability of organ preservation is not settled.","Quality of life and bowel function after watch and wait against surgery are reported separately and are not uniformly better."],"changedPractice":true,"participants":324},"route":"/key-papers/paper-garcia-aguilar-opra-organ-preservation-jco-2022/","neighbours":{"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-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/"}],"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":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"trial":[{"id":"opra","kind":"trial","name":"OPRA","route":"/trials/opra/"}],"person":[{"id":"andrea-cercek","kind":"person","name":"Andrea Cercek","route":"/people/andrea-cercek/"},{"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/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"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/"}],"idea":[{"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","route":"/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/"}]}}