Incidence and Outcomes of Secondary Bladder Cancer Following Radiation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis

There is an established association between secondary bladder cancers (SBCs) and radiotherapy (RT) for prostate cancer (PC), which remains a significant concern. Our aim was to update the evidence on SBC incidence across different RT modalities and to compare oncological outcomes for patients diagnosed with SBC to those diagnosed with primary bladder cancer (PBC). We searched MEDLINE, Scopus, and Web of Science for studies on SBC following PC. Pairwise meta-analyses were conducted to compare SBC incidence in terms of odds ratios (ORs) between RT modalities (external beam radiation therapy [EBRT], brachytherapy [BT], and BT + EBRT) and PBC incidence after radical prostatectomy (RP). SBC incidence data are presented as proportions, and pairwise meta-analyses were used to compare overall survival (OS) between SBC and PBC using hazard ratios (HRs). Thirty-one studies (n = 576 341) were included. All RT modalities significantly increased the risk of SBC in comparison to RP at all time points investigated. BT alone had similar long-term SBC risk in comparison to EBRT (OR 0.56, 95% confidence interval [CI] 0.25-1.23 at 10 yr; OR 0.51, 95% CI 0.24-1.06 at 15 yr). There was no significant difference in OS between SBC and PBC in the overall cohort. However, among patients requiring radical cystectomy (RC), SBC resulted in a significant decrease in OS in comparison to PBC (HR 1.55, 95% CI 1.06-2.26; p = 0.02). All RT modalities increased the risk of SBC at each post-RT time point investigated. SBC patients requiring RC have worse survival than those with PBC. Our results highlight the need for ongoing surveillance and early detection. Despite the rarity of SBC, clinicians should monitor bladder symptoms in PC patients after RT. These data need to be included in the shared decision-making process with patients regarding therapeutic decisions to raise awareness of SBC in this setting.