{"entity":{"id":"paper-sauer-preoperative-chemoradiotherapy-rectal-nejm-2004","kind":"paper","name":"Sauer 2004: chemoradiotherapy before rather than after surgery for rectal cancer (CAO/ARO/AIO-94)","aka":[],"tldr":"Giving chemotherapy and radiotherapy before surgery rather than after halved local recurrences of rectal cancer, caused less toxicity and let more patients keep their anal sphincter, without changing overall survival.","summary":"The German Rectal Cancer Study Group randomised 823 patients with locally advanced rectal cancer (clinical stage T3 or T4 or node-positive) to fluorouracil-based chemoradiotherapy either before or after total mesorectal excision, with both groups receiving further chemotherapy. Preoperative treatment reduced five-year local recurrence, lowered acute and long-term toxicity and increased sphincter-preserving surgery among patients whose tumours had been judged to need an abdominoperineal resection, while overall survival was the same in both arms.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa040694"}],"tags":[],"related":["colorectal-roadmap","paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009","paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["chemoradiation","neoadjuvant-adjuvant","total-neoadjuvant-therapy","organ-preservation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa040694","authors":"Sauer R, Becker H, Hohenberger W, et al.","paperType":"rct","findings":["823 patients with locally advanced rectal cancer; chemoradiotherapy before or after total mesorectal excision.","Five-year local recurrence 6% with preoperative vs 13% with postoperative treatment.","Five-year overall survival 76% vs 74%, not significantly different.","Grade 3 or 4 acute toxicity 27% vs 40%; long-term toxicity 14% vs 24%; sphincter preservation rose in patients initially judged to need an abdominoperineal resection."],"whatItMeans":"This trial made preoperative chemoradiotherapy the standard for locally advanced rectal cancer worldwide and is the foundation on which total neoadjuvant therapy and watch-and-wait organ preservation were later built.","caveats":["Overall survival was unchanged; the gain is in local control, toxicity and function.","Chemotherapy was fluorouracil alone by the standards of 2004.","Staging relied on endorectal ultrasound and CT rather than modern MRI."],"changedPractice":true,"participants":823},"route":"/key-papers/paper-sauer-preoperative-chemoradiotherapy-rectal-nejm-2004/","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/"}],"paper":[{"id":"paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001","kind":"paper","name":"Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer (Dutch TME trial)","route":"/key-papers/paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001/"},{"id":"paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009","kind":"paper","name":"Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016)","route":"/key-papers/paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"organ-preservation","kind":"term","name":"Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)","route":"/terms/organ-preservation/"},{"id":"total-neoadjuvant-therapy","kind":"term","name":"Total neoadjuvant therapy (TNT, rectal cancer)","route":"/terms/total-neoadjuvant-therapy/"}],"trial":[{"id":"cao-aro-aio-94","kind":"trial","name":"CAO/ARO/AIO-94 (German Rectal Cancer Study)","route":"/trials/cao-aro-aio-94/"}]}}