{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:08:41Z","timestamp":1791562121269,"version":"4.3.4"},"reference-count":188,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Institute Hospital, Japanese Foundation for Cancer Research"},{"id":[{"id":"https:\/\/ror.org\/00bv64a69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Perioperative treatment for colorectal cancer (CRC) is undergoing a paradigm shift from uniform cytotoxic regimens toward strategies guided by tumor location, microsatellite instability (MSI)\/mismatch repair (MMR) status, and recurrence risk. Four clinically relevant subgroups now shape decision-making: microsatellite stable (MSS)\/proficient MMR (pMMR) colon cancer, microsatellite instability-high (MSI-H)\/deficient MMR (dMMR) colon cancer, MSS\/pMMR rectal cancer, and MSI-H\/dMMR rectal cancer. In MSS\/pMMR colon cancer, adjuvant therapy is being refined through risk-adapted treatment duration and selective use of neoadjuvant chemotherapy. In MSS\/pMMR rectal cancer, total neoadjuvant therapy, selective omission of pelvic radiotherapy, and watch-and-wait strategies are redefining treatment sequencing and organ preservation. In MSI-H\/dMMR colon cancer, immune checkpoint inhibitor (ICI) therapy has shown marked activity in both adjuvant and neoadjuvant settings. In MSI-H\/dMMR rectal cancer, neoadjuvant ICI therapy is being explored as a non-operative organ preservation strategy. In parallel, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assessment is emerging as a tool for postoperative escalation, de-escalation, and surveillance. Across these settings, the maturity of the evidence varies widely, ranging from established phase III standards to guideline-endorsed but still single-arm approaches and investigational strategies that require prospective validation before routine adoption. This review summarizes the current evidence and remaining challenges in biology-, site-, and risk-adapted perioperative management of CRC.<\/jats:p>","DOI":"10.3390\/ijms27167261","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"7261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Paradigm Shifts in Perioperative Management of Colorectal Cancer: Personalization Based on Tumor Biology, Primary Site, and Recurrence Risk, and the Evolving Role of Organ Preservation"],"prefix":"10.3390","volume":"27","author":[{"given":"Kaoru","family":"Yoshikawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7618-5775","authenticated-orcid":false,"given":"Akira","family":"Ooki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-5894","authenticated-orcid":false,"given":"Eiji","family":"Shinozaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8220-0282","authenticated-orcid":false,"given":"Eiichiro","family":"Toyokawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keito","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1912-5948","authenticated-orcid":false,"given":"Manabu","family":"Shiozawa","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Kanagawa Cancer Center, Yokohama 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-1594","authenticated-orcid":false,"given":"Shin","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6887-5709","authenticated-orcid":false,"given":"Kensei","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4742-0446","authenticated-orcid":false,"given":"Hiroki","family":"Osumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kanagawa Cancer Center, Yokohama 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0140-6736(24)00360-X","article-title":"Colorectal Cancer","volume":"404","author":"Eng","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1056\/NEJMoa032709","article-title":"Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer","volume":"350","author":"Boni","year":"2004","journal-title":"N. 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