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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.
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.
Patients 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.
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.
For mismatch repair-deficient rectal cancer, six months of a single antibody now replaces chemotherapy, radiotherapy and an operation, and the same appears to be true for early-stage mismatch repair-deficient cancers of other organs.
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.
The origin of organ preservation in rectal cancer. Twenty years later OPRA made it a planned strategy and the dostarlimab series made it the expected outcome in mismatch repair-deficient disease.
Shares Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO), Total neoadjuvant therapy (TNT, rectal cancer), Total mesorectal excision (TME), Radiotherapy and the tag colorectal-evidence.
Shares Total mesorectal excision (TME), Radiotherapy, Surgery and radiotherapy cure most, get least, 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 and the tag colorectal-evidence.
Shares Total mesorectal excision (TME), Radiotherapy, Surgery and radiotherapy cure most, get least, MRI and the tag colorectal-evidence.
Shares Total mesorectal excision (TME), Radiotherapy, Surgery and radiotherapy cure most, get least, 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 and the tag colorectal-evidence.
Shares Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO), Total mesorectal excision (TME), Radiotherapy, MRI and the tag colorectal-evidence.
Shares Surgery and radiotherapy cure most, get least, CAPOX (capecitabine, oxaliplatin), 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Total mesorectal excision (TME), Surgery and radiotherapy cure most, get least, 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, Rectal cancer and the tag colorectal-evidence.
Shares CAPOX (capecitabine, oxaliplatin), 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, FOLFOX (5-FU, leucovorin, oxaliplatin), Toxicity and quality of life are undervalued and the tag colorectal-evidence.