{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:02:21Z","timestamp":1791388941393,"version":"4.3.3"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"\n Importance<\/jats:title>\n The definition of cure in stage II to III colon cancer (CC) remains unclear due to limitations in conventional end points, which include deaths and second primary tumors as events. These can complicate communication with patients regarding long-term outcomes.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To distinguish relapses from competing health-related events to classify long-term outcomes years after surgery and explore when the incidence of true relapses of the initial CC approaches 0% to define cure in this disease.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This pooled analysis of individual patient\u2013level data from 15 phase 3 randomized clinical trials assessed time to CC-related relapse using Kaplan-Meier and Aalen-Johansen methods, with death and second primary tumors treated as competing risks. Cox regression models evaluated prognostic associations, stratified by sex, stage, and tumor. Patients with stage II to III CC who underwent adjuvant chemotherapy were included. All patients had undergone radical surgery for CC and received adjuvant chemotherapy with a median follow-up of at least 6 years. The Adjuvant Colon Cancer Endpoints (ACCENT) and the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) databases included adjuvant studies conducted between 1996 and 2015. Data were analyzed from February 2022 to June 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Adjuvant chemotherapy regimens varied across trials, including fluoropyrimidines alone or in combination with oxaliplatin or biologic agents.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was time to CC-related recurrence. The predefined threshold for cure was a recurrence risk below 0.5%.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 35\u202f213 included patients, 19 346 (54.9%) were male, and the mean (SD) age was 60.2 (10.8) years. The incidence rate of recurrence peaked at 6.4% (1993 of 31\u202f373) between month 6 and month 12 and decreased continuously until year 10 of follow-up never exceeding 0.5%. Recurrence rate appeared to increase again after year 10 and peaked at 2.0% during year 12.5 to year 13, a pattern observed exclusively in the MOSAIC trial. Competing-event analysis revealed that death and second primary tumors inflated the apparent recurrence rate, especially for older patients. The overall cumulative incidence of relapse with death as competing risk was lower among female patients (hazard ratio, 0.58; 95% CI, 0.45-0.76;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this pooled analysis of phase 3 randomized clinical trials, a recurrence rate less than 0.5% occurred after 6 years from surgery, supporting a practical definition of cure. Recognizing this milestone may improve patient communication, guide follow-up duration, and reduce unnecessary long-term surveillance.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2025.3760","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:31:32Z","timestamp":1759419092000},"page":"1440","source":"Crossref","is-referenced-by-count":8,"title":["The Definition of Cure in Colon Cancer"],"prefix":"10.1001","volume":"11","author":[{"given":"Alessandro","family":"Pastorino","sequence":"first","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Medical Oncology Unit 1, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, 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