Abstract 4674: Pathological outcomes of short course vs. long course neoadjuvant radiation for stage II/III rectal cancer

Abstract Background: Total neoadjuvant therapy for rectal cancer has emerged as a favorable treatment plan. However, a definitive treatment algorithm has not been identified. Our study compares pathological response rates for neoadjuvant induction therapy regarding short and long course radiation across various demographic and disease-specific criteria. Methods: Using the National Cancer Database (NCDB), data were collected for patients with clinical stage II and III rectal cancer who underwent neoadjuvant induction chemoradiation with either short or long course radiation from 2004-2021. Chi-squared test was used to compare the proportion of pathologic downstaging, pathologic compete response, positive surgical margin, and decreasing T and N stages individually for short course versus long course radiation. Logistic regression was used to perform multivariable analysis of factors impacting pathologic downstaging. Kaplan-Meier survival curves were used to compare overall survival between groups. Results: A total of 1, 470 patients underwent induction chemoradiation for stage II or III rectal cancer; 293 underwent short course radiation, while 1, 177 underwent long course. Patients with stage II/III rectal cancer who underwent long course radiation were more likely to achieve pathologic downstaging (OR 1.83 [1.13, 2.97]) and decreasing T stage (OR 1.82 [1.14, 2.95]). On multivariate analysis, patients who received care at a community cancer program were less likely to achieve pathologic downstaging than those who received care at an academic program (OR 0.35 [0.14, 0.87]), patients with initial cN1 and cN2 tumors were more likely to achieve pathologic downstaging than those with cN0 tumors (OR 2.86 [1.94, 4.22] and OR 3.20 [1.80, 5.68], respectively), and patients who underwent long course radiation were more likely to achieve pathologic downstaging than those who underwent short course (OR 2.04 [1.19, 3.47]). Overall survival was improved for the long course group compared to the short course group (p=0.02). Median overall survival was 165 months for patients who underwent long course radiation and 104 months for those who underwent short course radiation. Conclusion: Based on a retrospective review of NCDB data from 2004-2021, patients who underwent induction therapy with long course radiation for stage II/III rectal cancer were more likely to achieve pathologic downstaging than those who underwent short course radiation. Furthermore, overall survival was improved in patients who underwent long course radiation. This leads us to recommend long course over short course neoadjuvant radiation in induction therapy of patients with stage II/III rectal cancer. Given the extended median overall survival reported here, we call for long-term follow-ups from the randomized clinical trials reporting on long course vs short course radiation before the controversy can be settled. Citation Format: Alyssa Habermann, Patrick Chizek, Xiaoyan Deng, Dipankar Bandyopadhyay, Adam Khader, Stephen P. Sharp. Pathological outcomes of short course vs. long course neoadjuvant radiation for stage II/III rectal cancer [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 4674.