Management of Locally Advanced Rectal Cancer

Published ahead of print August 8, 2024, DOI: 10.1200/JCO.24.01160

Aaron J. Scott, Erin B. Kennedy, Jordan Berlin, Gina Brown, Myriam Chalabi, May T. Cho, Mike Cusnir, Jennifer Dorth, Manju George, Lisa A. Kachnic, Hagen F. Kennecke, Jonathan M. Loree, Van K. Morris, Rodrigo Oliva Perez, J. Joshua Smith, Matthew R. Strickland, and Sepideh Gholami

Purpose

To provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer.

Methods

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.

Results

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.

Recommendations

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 totalmesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended.

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