High prevalence of secondary bladder cancer in men on radiotherapy for prostate cancer: evidence from a meta-analysis

Objective: To assess whether radiotherapy (RT) for prostate cancer (PCa) was a risk factor for secondary bladder cancer (BLCa) through a meta-analysis. Materials and methods: The MEDLINE, Embase, and the Cochrane Library were systematically searched for all studies investigating the risk of BLCa in patients with RT. The association between RT and risk of BLCa was summarized using hazard ratio with a 95% CI. The protocol for this meta-analysis is available from PROSPERO (CRD42018090075). Results: Overall, 619,479 participants (age: 57-79 years) were included from 15 studies, 206,852 of whom were patients who received RT. Synthesis of results indicated that RT was significantly associated with an increased risk of BLCa compared with the risk in those who received radical prostatectomy or non-RT (overall HR=1.6, 95% CI: 1.33-1.92, P<0.001). The results were consistent when restricted to a 5-year lag period (HR=1.84, 95% CI: 1.26-2.69, P=0.002) and multivariable adjustment (HR=1.96, 95% CI: 1.47-2.62, P<0.001), but not for 10-year lag period (HR=1.93, 95% CI: 0.9-4.16, P=0.093) and brachytherapy subgroup (HR=1.33, 95% CI: 0.87-2.05, P=0.188). The GRADE-profiler revealed that the rate of events of BLCa on average in the RT-patients and the non-RT control was 2,462/183,669 (1.3%) and 4,263/382,761(1.1%), respectively; the overall quality of the evidence was low. Conclusion: Patients who received RT for PCa was associated with higher risks of developing secondary BLCa compared to those unexposed to RT, but the absolute effect was low.