Abstract 5943: The impact of radiotherapy on prognosis in microsatellite stable rectal cancer: A national analysis

Background: Approximately 80-85% of rectal cancer cases are microsatellite stable (MSS), indicating a functional mismatch repair (MMR) system. Rectal cancer patients with microsatellite instability (MSI) exhibit better survival rates, mainly due to enhanced treatment responses linked to high tumor mutational burden (TMB). Radiotherapy (RT) induces DNA damage, increasing TMB and immune recognition. We hypothesize that RT improves prognosis in MSS rectal cancer patients. Methods: A retrospective study was conducted using the National Cancer Database (NCDB), including patients aged ≥20 years diagnosed with MSS rectal cancer between 2004 and 2020 with documented tumor stages. All patients underwent surgical resection, chemotherapy, and immunotherapy. Collected data encompassed demographics, tumor grade, TNM stage, KRAS mutation status, lymphovascular invasion, and perineural invasion. RT was categorized into short-course RT (SC-RT; 25 Gy) and long-course RT (LC-RT; 45-54 Gy). The impact of RT on overall survival was assessed using multivariable Cox proportional hazards regression, adjusting for variables significant in univariate analysis. Results: Of the 460 patients included, 70.9% received RT, while 29.1% did not. RT recipients demonstrated a 40% reduction in mortality risk compared to non-recipients (P = 0.001). Specifically, SC-RT and LC-RT were associated with 39% (P = 0.042) and 40% (P = 0.002) lower mortality risks, respectively. In stage II-III patients, LC-RT significantly reduced mortality risk (HR: 0.26, P < 0.001), whereas SC-RT showed no significant impact. In stage IV patients, neither SC-RT nor LC-RT significantly affected prognosis. Conclusion: Radiotherapy is associated with improved prognosis in MSS rectal cancer patients, particularly with long-course RT in stages II-III. These findings advocate for clinical trials to further evaluate the role of RT in MSS rectal cancers. Citation Format: Mohyeddine El Sayed, Sassine Youssef, Raymond N. DuBois. The impact of radiotherapy on prognosis in microsatellite stable rectal cancer: A national analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5943.