{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:32:28Z","timestamp":1762367548970,"version":"build-2065373602"},"reference-count":16,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turkish Society of Colon and Rectal Surgery"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. However, nCRT is associated with significant morbidity, impacting patients\u2019 quality of life. Recent advancements in MRI-based risk stratification have raised the possibility of omitting nCRT in selected patients without compromising oncologic outcomes. This study aims to evaluate whether upfront TME alone achieves similar 3-year disease-free survival compared to the standard approach of nCRT followed by TME in patients with cT2N+ and cT3Nx mid-rectal cancer without MRI-based high-risk features regarding local recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The CANO trial is a prospective, multicenter, observational cohort study involving 436 patients across T\u00fcrkiye. Eligible patients will be classified into two groups: those undergoing direct TME and those receiving nCRT followed by TME. The primary endpoint is 3-year disease-free survival (DFS), with secondary outcomes including 5-year DFS, overall survival, local recurrence rates, and quality of life assessments using validated questionnaires. Data will be prospectively collected and monitored by the steering committee with predefined interim analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The CANO trial addresses the ongoing debate regarding selective omission of nCRT in low-risk mid-rectal cancer. By leveraging MRI-based risk stratification and a collaborative national network, the study aims to provide high-quality evidence supporting a more personalized treatment approach. The findings have the potential to reduce treatment-related morbidity without compromising oncologic safety, contributing to the refinement of current guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT06823297 [registered before starting inclusion; Version 8, 23.06.2025].<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0321819","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T18:29:54Z","timestamp":1762367394000},"page":"e0321819","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Can neoadjuvant chemoradiotherapy be omitted in cT2N+ and cT3 mid-rectal cancer: Protocol for a prospective, observational, cohort study (CANO)"],"prefix":"10.1371","volume":"20","author":[{"given":"Feza","family":"Karakayali","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-7207","authenticated-orcid":true,"given":"Cigdem","family":"Arslan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayfun","family":"Bisgin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4878-0873","authenticated-orcid":true,"given":"Ilknur","family":"Erenler Bayraktar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onur","family":"Bayraktar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8257-5881","authenticated-orcid":true,"given":"Aras Emre","family":"Canda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"issue":"5","key":"pone.0321819.ref001","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/01.sla.0000257358.56863.ce","article-title":"The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma","volume":"246","author":"KCMJ Peeters","year":"2007","journal-title":"Ann Surg"},{"issue":"9666","key":"pone.0321819.ref002","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0140-6736(09)60484-0","article-title":"Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial","volume":"373","author":"D Sebag-Montefiore","year":"2009","journal-title":"Lancet"},{"issue":"9","key":"pone.0321819.ref003","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1056\/NEJMoa010580","article-title":"Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer","volume":"345","author":"E Kapiteijn","year":"2001","journal-title":"N Engl J Med"},{"issue":"17","key":"pone.0321819.ref004","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJMoa040694","article-title":"Preoperative versus postoperative chemoradiotherapy for rectal cancer","volume":"351","author":"R Sauer","year":"2004","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0321819.ref005","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/00000658-200204000-00001","article-title":"Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery","volume":"235","author":"KF Birbeck","year":"2002","journal-title":"Ann Surg"},{"issue":"7","key":"pone.0321819.ref006","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s10350-004-6317-7","article-title":"A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment in Norway. 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