{"entity":{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","aka":["Rectal adenocarcinoma","Cancer of the rectum","Locally advanced rectal cancer","Rectum cancer"],"tldr":"Rectal cancer is bowel cancer in the last part of the large intestine, where surgery can mean a permanent stoma. Treatment now usually gives all the chemotherapy and radiotherapy first, and about half of people whose tumour disappears completely can keep their rectum and avoid surgery altogether.","summary":"Rectal cancer is staged by pelvic MRI, which shows the depth of invasion, the distance to the mesorectal fascia, extramural venous invasion and nodal disease and so decides who needs treatment before surgery. Total mesorectal excision, described by Heald in 1982, cut local recurrence from a quarter of patients to well under a tenth, and the German CAO/ARO/AIO-94 trial (2004) moved chemoradiation to before surgery, halving local recurrence again. Early tumours (cT1-2, node-negative) go straight to surgery, and small T1 tumours can be removed through the anus.\n\nFor locally advanced disease the sequence has been rebuilt as total neoadjuvant therapy: RAPIDO (2020) gave one week of radiotherapy then all the chemotherapy before surgery and cut distant failure and doubled complete responses; PRODIGE 23 (2021) gave induction mFOLFIRINOX before chemoradiation and improved disease-free and, later, overall survival. OPRA (2022) showed that with chemoradiation followed by consolidation chemotherapy about half of patients could avoid surgery through watch and wait without losing disease control, building on the Habr-Gama series from Sao Paulo. PROSPECT (2023) then showed that intermediate-risk tumours suitable for sphincter-sparing surgery can be treated with FOLFOX alone, with radiotherapy reserved for the 9 percent who do not respond.\n\nThe 5 to 10 percent of rectal cancers that are mismatch-repair deficient respond so completely to PD-1 blockade that surgery and radiotherapy can be omitted: in the Memorial Sloan Kettering study every patient treated with six months of dostarlimab had a clinical complete response (NEJM 2022, expanded 2025), and AZUR-1 is the registration study. Metastatic rectal cancer is treated as metastatic colorectal cancer, by genotype and sidedness. Open questions are how to select watch and wait safely, whether circulating tumour DNA can guide surveillance, and how to reduce the bowel, sexual and urinary harm that survivors carry.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Colorectal_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Colorectal_cancer"},{"label":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":["imrt-igrt","hypofractionated-radiotherapy","robotic-surgery","mri","checkpoint-inhibitor"],"targets":["pd1","egfr","vegf"],"drugs":["folfox","capox","dostarlimab","fluorouracil","capecitabine"],"companies":[],"institutions":[],"pathways":["colorectal-cancer-signalling"],"terms":["total-neoadjuvant-therapy","organ-preservation","clinical-complete-response","total-mesorectal-excision","chemoradiation","stoma","msi"],"trials":["rapido","prodige-23","opra","prospect","cao-aro-aio-94","azur-1","nct06640049"],"people":["angelita-habr-gama","julio-garcia-aguilar","andrea-cercek","luis-diaz"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"About a third of colorectal cancers start in the rectum, the last 15 cm of the bowel; because the rectum sits in the narrow pelvis next to the bladder, sexual organs and sphincter, local recurrence, stomas and function matter more than for colon cancer.","subtypes":["Low rectal cancer (within 5 cm of the anal verge; the sphincter is at risk)","Mid and upper rectal cancer (anterior resection with anastomosis)","Locally advanced rectal cancer (cT3-4 or node-positive on MRI; total neoadjuvant therapy)","Mismatch-repair deficient rectal cancer (immunotherapy alone, no surgery)","Rectal cancer in clinical complete response under watch and wait"],"biomarkers":["Pelvic MRI: T stage, mesorectal fascia involvement, extramural venous invasion, lateral nodes","Mismatch repair / microsatellite status (immunotherapy alone if deficient)","RAS, BRAF V600E and HER2 in metastatic disease","Carcinoembryonic antigen (CEA)","Circulating tumour DNA after treatment (under study)","Clinical complete response on endoscopy and MRI"],"standardOfCare":[{"setting":"Early (cT1-2, node-negative)","approach":"Total mesorectal excision, increasingly robotic or laparoscopic; transanal local excision for small, well-differentiated T1 tumours; no radiotherapy.","refs":["total-mesorectal-excision","robotic-surgery","mri"],"guideline":{"version":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}},{"setting":"Locally advanced, higher risk","approach":"Total neoadjuvant therapy: short-course radiotherapy then CAPOX or FOLFOX (RAPIDO), or induction mFOLFIRINOX then chemoradiation (PRODIGE 23); chemoradiation then consolidation chemotherapy when organ preservation is the goal (OPRA); surgery or watch and wait for complete responders.","refs":["rapido","prodige-23","opra","capox","folfox","hypofractionated-radiotherapy","total-neoadjuvant-therapy","organ-preservation","clinical-complete-response"],"guideline":{"version":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}},{"setting":"Intermediate risk, sphincter-sparing surgery planned","approach":"Six cycles of FOLFOX with chemoradiation only if the tumour shrinks by less than 20 percent (PROSPECT), then total mesorectal excision.","refs":["prospect","folfox","chemoradiation","total-mesorectal-excision"],"guideline":{"version":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}},{"setting":"Mismatch-repair deficient","approach":"Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders; surgery reserved for the rare non-responder.","refs":["dostarlimab","azur-1","msi","organ-preservation"],"guideline":{"version":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}},{"setting":"Metastatic","approach":"As metastatic colorectal cancer: doublet chemotherapy with bevacizumab or, for RAS and BRAF wild-type left-sided tumours, an anti-EGFR antibody; primary tumour managed by symptoms; liver-limited disease resected.","refs":["folfox","folfiri","bevacizumab","cetuximab","panitumumab","hepatectomy"],"guideline":{"version":"NCCN Guidelines: Rectal Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461"}}],"stateOfArt":["Total neoadjuvant therapy (RAPIDO, PRODIGE 23, OPRA) has replaced chemoradiation then surgery then chemotherapy as the default for locally advanced disease.","Watch and wait after clinical complete response spares about half of selected patients the operation, with salvage surgery for the regrowths.","PROSPECT removed pelvic radiotherapy from the pathway for intermediate-risk tumours.","Mismatch-repair deficient rectal cancer is treated with immunotherapy alone."],"history":[{"year":1908,"title":"Miles describes the abdominoperineal resection with permanent colostomy","refs":["abdominoperineal-resection"]},{"year":1982,"title":"Heald describes total mesorectal excision, cutting local recurrence to under 10 percent","refs":["total-mesorectal-excision"]},{"year":2004,"title":"CAO/ARO/AIO-94: preoperative chemoradiation halves local recurrence","refs":["cao-aro-aio-94"]},{"year":2004,"title":"Habr-Gama reports watch and wait after complete clinical response in Sao Paulo","refs":["angelita-habr-gama","organ-preservation"]},{"year":2020,"title":"RAPIDO: short-course radiotherapy then chemotherapy establishes total neoadjuvant therapy","refs":["rapido","total-neoadjuvant-therapy"]},{"year":2021,"title":"PRODIGE 23: induction mFOLFIRINOX improves disease-free survival","refs":["prodige-23"]},{"year":2022,"title":"OPRA: about half of patients keep their rectum after total neoadjuvant therapy","refs":["opra","julio-garcia-aguilar"]},{"year":2022,"title":"Dostarlimab alone produces complete responses in every mismatch-repair deficient rectal cancer treated","refs":["dostarlimab","andrea-cercek","luis-diaz"]},{"year":2023,"title":"PROSPECT: FOLFOX with selective chemoradiation is as good as routine chemoradiation","refs":["prospect"]},{"year":2026,"title":"AZUR-1 confirms non-operative management with dostarlimab in mismatch-repair deficient rectal cancer","refs":["azur-1"]}],"pipeline":["azur-1","nct06640049","dostarlimab","signatera","idea-ctdna-guided-adjuvant-crc"],"openProblems":["No validated test predicts which clinical complete responders will regrow under watch and wait.","Long-term bowel, sexual and urinary function after total neoadjuvant therapy is poorly measured.","Whether circulating tumour DNA can safely guide surveillance after organ preservation is untested in randomised trials.","Lateral pelvic node disease is managed differently in Japan and the West with no comparative trial."],"parent":"colorectal"},"route":"/cancers/rectal-cancer/","neighbours":{"technology":[{"id":"hypofractionated-radiotherapy","kind":"technology","name":"Hypofractionated radiotherapy","route":"/technologies/hypofractionated-radiotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"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/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"capox","kind":"drug","name":"CAPOX (capecitabine, oxaliplatin)","route":"/drugs/capox/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, irinotecan)","route":"/drugs/folfiri/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"pathway":[{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"}],"term":[{"id":"abdominoperineal-resection","kind":"term","name":"Abdominoperineal resection","route":"/terms/abdominoperineal-resection/"},{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"clinical-complete-response","kind":"term","name":"Clinical complete response (cCR)","route":"/terms/clinical-complete-response/"},{"id":"hepatectomy","kind":"term","name":"Hepatectomy (liver resection)","route":"/terms/hepatectomy/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"organ-preservation","kind":"term","name":"Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)","route":"/terms/organ-preservation/"},{"id":"stoma","kind":"term","name":"Stoma (colostomy, ileostomy, urostomy)","route":"/terms/stoma/"},{"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/"}],"trial":[{"id":"nct06640049","kind":"trial","name":"A Study of Dostarlimab in Participants With Untreated Locally Advanced Rectal Cancer in China","route":"/trials/nct06640049/"},{"id":"azur-1","kind":"trial","name":"AZUR-1","route":"/trials/azur-1/"},{"id":"cao-aro-aio-94","kind":"trial","name":"CAO/ARO/AIO-94 (German Rectal Cancer Study)","route":"/trials/cao-aro-aio-94/"},{"id":"opra","kind":"trial","name":"OPRA","route":"/trials/opra/"},{"id":"prodige-23","kind":"trial","name":"PRODIGE 23","route":"/trials/prodige-23/"},{"id":"prospect","kind":"trial","name":"PROSPECT (Alliance N1048)","route":"/trials/prospect/"},{"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/"},{"id":"luis-diaz","kind":"person","name":"Luis A. Diaz Jr.","route":"/people/luis-diaz/"}],"idea":[{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}]}}