The Impact of Intraoperative Radiotherapy on Margin Positive Locally Advanced Rectal Cancer: A Propensity-Matched Analysis of The National Cancer Database.

Purpose: Intraoperative radiotherapy (IORT) is utilized as an adjunctive treatment in advanced rectal cancer, particularly in cases with threatened surgical margins. Although IORT has shown benefits in enhancing local tumor control, its impact on overall survival (OS) remains unclear. This study assesses the effect of IORT on survival outcomes using a large cohort from the National Cancer Database (NCDB) and examines factors influencing its application in clinical practice across the United States.

Methods: The National Cancer Database was retrospectively reviewed (2006-2019) to identify patients with pathological T3-T4, M0 rectal cancer who underwent surgery following neoadjuvant chemotherapy. Patients with microscopically residual margin-positive were included and categorized into two groups: those who received neoadjuvant radiotherapy (RT) and those treated with intraoperative radiotherapy (IORT) combined with adjuvant/neoadjuvant RT. Groups were propensity score-matched (1:4) to balance baseline characteristics. The primary outcome was 5-year overall survival (OS), assessed using Kaplan-Meier analysis and Cox proportional hazards modeling.

Results: Among 1,788 patients with margin-positive rectal cancer, IORT was administered to 119 patients (6.7%) while 1,669 patients (93.3%) received neoadjuvant RT. Patients receiving IORT were younger, more likely to have private insurance, more frequently treated at academic/research programs, and more commonly underwent pelvic exenteration and Multiagent chemotherapy. After propensity score matching, 119 IORT patients were compared with 476 neoadjuvant RT patients. IORT was associated with lower mortality in univariate analysis (HR: 0.63; p < 0.001); however, this benefit was attenuated after adjusting for confounders (HR: 0.84; p = 0.07). The 5-year overall survival rates were 58.4% for IORT versus 54.9% for neoadjuvant RT alone (p = 0.18).

Conclusion: This nationwide analysis suggests that adding IORT to treatment does not significantly improve overall survival in margin-positive rectal cancer patients. However, due to heterogeneity in patient selection and dosing, further prospective trials are warranted to clarify its clinical role.