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ASCO Guidelines follow the\n ASCO Conflict of Interest Policy for Clinical Practice Guidelines<\/jats:ext-link>\n <\/jats:italic>\n .\n <\/jats:p>\n \n \n Clinical Practice Guidelines and other guidance (\u201cGuidance\u201d) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in\n Appendix 1<\/jats:xref>\n and\n 2<\/jats:xref>\n <\/jats:italic>\n (online only) for more<\/jats:italic>\n .\n <\/jats:p>\n \n PURPOSE<\/jats:title>\n To provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n A systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Twelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.<\/jats:p>\n <\/jats:sec>\n \n RECOMMENDATIONS<\/jats:title>\n Following assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and\/or patients who are at higher risk for local and\/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. 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