SHORT- VERSUS LONG-COURSE RADIATION IN TOTAL NEOADJUVANT THERAPY FOR LOCALLY ADVANCED RECTAL CANCER: A PROPENSITY-MATCHED NATIONAL CANCER DATABASE ANALYSIS

BACKGROUND: Locally advanced rectal cancer is treated with total neoadjuvant therapy which consists of neoadjuvant chemotherapy, radiation, and surgery. The comparative efficacy of long and short course radiotherapy within total neoadjuvant therapy remains uncertain. OBJECTIVE: Compare overall survival and pathological outcomes between patients treated with long or short course radiation as components of total neoadjuvant therapy. DESIGN: Retrospective cohort study. SETTINGS: National Cancer Database, 2018 to 2023. PATIENTS: Adults with clinical Stage II or III rectal adenocarcinoma treated with neoadjuvant chemotherapy and radiation followed by radical surgical resection. MAIN OUTCOME MEASURES: Overall survival and pathological outcomes in a propensity score matched cohort comparing long and short course radiation. RESULTS: A total of 12,462 patients met inclusion criteria; 10,740 (86.2%) received long course radiation and 1,722 (13.8%) received short course radiation. After 1:1 propensity score matching, 1,721 per group were identified. Overall survival at 48 months did not differ (log rank p = 0.397). There were no differences in pathological complete response rate, pathological tumor stage, tumor downstaging, or pathological nodal stage. The long course radiotherapy group had higher nodal downstaging (66.5 vs 62.7%, p = 0.023) and a nonsignificant trend towards lower nodal disease (N0 73.9 vs 70.7%, N1 21.5 vs 23.3%, and N2 4.6 vs 6.0%, respectively, p = 0.062). LIMITATIONS: Residual confounding from unmeasured clinical and treatment details is possible. This cohort was restricted to patients who underwent resection. CONCLUSIONS: Among locally advanced rectal cancer patients treated with total neoadjuvant therapy and radical resection, long and short course radiotherapy had similar overall survival, but long course radiotherapy patients had higher rates of nodal downstaging. These findings support the use of either long or short course radiotherapy regimens when planned resection is intended, but the clinical significance of differences in nodal downstaging remain uncertain. See Video Abstract.