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Giving all the chemotherapy and radiotherapy for rectal cancer before surgery rather than splitting it around the operation. It improves completion of chemotherapy, shrinks more tumours completely, and makes avoiding surgery possible for some patients.
Classic management was chemoradiation, surgery, then adjuvant FOLFOX, which a large share of patients never completed. TNT (RAPIDO: short-course radiotherapy then FOLFOX/CAPOX; PRODIGE 23: FOLFIRINOX then chemoradiation) halved distant metastases and doubled pathological complete responses, and OPRA showed that with consolidation chemotherapy about half of patients can be managed by watch-and-wait without surgery. PROSPECT showed FOLFOX alone can replace radiotherapy in selected intermediate-risk tumours, and dMMR rectal cancer is now treated with dostarlimab alone. The optimal sequence and who can safely skip which component remain active questions.
Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.
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.
The second total neoadjuvant therapy schedule to change practice, and the one that shows the advantage is partly deliverability: chemotherapy given before an operation is completed by far more patients than chemotherapy given after one.
The first total neoadjuvant therapy trial to change practice in high-risk rectal cancer, and the schedule that makes organ preservation possible by giving the tumour months rather than weeks to respond.
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.
Shares OPRA, Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA), Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint, 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.
Shares Watch and wait after chemoradiotherapy for rectal cancer, OPRA, Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA), Organ preservation (watch-and-wait, bladder-sparing, larynx preservation).
Shares Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA), Organ preservation (watch-and-wait, bladder-sparing, larynx preservation), Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint, Chemoradiation (chemoradiotherapy, CRT).
Shares Sauer 2004: chemoradiotherapy before rather than after surgery for rectal cancer (CAO/ARO/AIO-94), Total mesorectal excision (TME), Chemoradiation (chemoradiotherapy, CRT), 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.
Shares Organ preservation (watch-and-wait, bladder-sparing, larynx preservation), Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint, Chemoradiation (chemoradiotherapy, CRT), Rectal cancer.
Shares Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23), Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint, Chemoradiation (chemoradiotherapy, CRT), 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.
Shares Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO), Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint, Early-onset colorectal cancer (under 50), 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.
Shares Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO), Total mesorectal excision (TME), Chemoradiation (chemoradiotherapy, CRT), Rectal cancer.