PURPOSE: We aimed to explore the risk of secondary prostate cancer (SPC) and secondary bladder cancer (SBC) in male rectal cancer (RC) patients after radiotherapy (RT) and to assess survival outcomes. METHODS: This large population-based study included men with RC from nine registries in the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2015. Fine-Gray competing risks and Poisson regression were used to assess the RT-related risk of SPC and SBC in patients who received RT versus those who did not (NRT). RESULTS: After exclusion, 28,886 RC patients were included in further analysis, including 9763 RT-treated patients (33.8%) and 19,123 patients not treated with RT (66.2%). In competing risk regression analysis, RT was associated with a low risk of developing SPC (adjusted HR = 0.67
95% CI = 0.64-0.82
P <
0.001) and with a high risk of developing SBC (adjusted HR = 1.44
95% CI = 1.15-1.80
P = 0.001). In the survival analysis of SPC patients, the NRT group exhibited better 10-year OS and CSS than the RT group (OS: HR = 0.52
95% CI = 0.43-0.64
P <
0.001
CSS: HR = 0.39
95% CI = 0.26-0.56
P <
0.001). CONCLUSION: Male rectal cancer patients receiving RT had a decreased risk of SPC and an increased risk of SBC, and the prognosis of SPC patients in the RT group was worse compared to that of the NRT group. Follow-up and monitoring of SBC and SPC should not be ignored.