Risk of secondary bladder cancer after postoperative radiotherapy for rectal cancer: A population-based cohort study

This study aimed to investigate the risk of secondary bladder cancer (SBC) among rectal cancer patients receiving rectal radiotherapy.

We conducted a large population-based cohort study to evaluate the risk of secondary bladder cancer (SBC) development in patients diagnosed with rectal cancer between January 1973 and December 2015. The study utilized data from nine cancer registries within the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, USA. SBC was operationally defined as cases diagnosed more than five years following the initial rectal cancer diagnosis. Cumulative incidence of SBC was calculated using Fine-Gray competing risk regression models. Poisson regression analyses were employed to quantify SBC risk among study participants. Survival outcomes for SBC patients were assessed through Kaplan-Meier survival analysis.

Out of a total of 45,710 patients, 14,253 underwent radiotherapy while 31,457 were treated with NRT. Over a 30-year follow-up period, the cumulative incidence of SBC was 0.97 % in the radiotherapy group compared to 0.49 % in the no radiotherapy (NRT) group. The competing risk regression analysis revealed that radiotherapy was associated with SBC (adjusted HR, 1.81; 95 % CI, 1.41-2.33, P = 0.0001), and the association was different with gender, for male patients (adjusted HR, 1.5; 95 % CI, 1.13-2, P = 0.019) and female patients (adjusted HR, 2.5; 95 % CI, 0.4-4.2, P = 0.0036). The dynamic prediction model indicates that radiotherapy significantly reduces the risk of SBC with increasing age and time since diagnosis. However, the risk of developing SBC increases with prolonged latency. The overall survival rate of male and female patients with and without radiotherapy-related SBC was not significantly different (HR,0.71; 95 % CI, 0.5-1.01). However, after propensity score matching, it was shown that the survival rate of SBC is significantly lower compared to primary bladder cancer (BC).

Radiotherapy for rectal cancer is associated with an increased risk of bladder cancer, and the risk is higher in female patients than in male patients. Special attention should be paid to SBC and improve their prognosis.

Clinicians should emphasize long-term bladder cancer surveillance following radiotherapy for rectal cancer, particularly in female patients and younger individuals. When evaluating radiotherapy regimens, the risk of secondary bladder cancer should be incorporated into patient-clinician discussions. We recommend implementing individualized screening protocols for high-risk populations:1 Initiate surveillance at 5 years post-radiotherapy and maintain for a minimum of 15 years (extended duration recommended for female patients)0.2 For male patients and those aged >40 years: Annual basic screening with urinalysis and urinary cytology. 3 For female patients and those aged <40 years: Annual cystoscopy or imaging examinations.