Abstract
PURPOSE: Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. CONCLUSION: In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.