Whether pelvic radiotherapy increased the risk of secondary bladder cancer? A systematic review and meta-analysis

Abstract Background The question whether pelvic radiotherapy increases the risk of secondary bladder cancer remains unclear. In this review, we aimed to demonstrate the relationship between exposure to radiation therapy for pelvic malignancies and subsequent second primary bladder cancer risk. Methods We systematically searched Medline, Embase and Web of Science for all associated studies concerning secondary bladder cancer risk and radiotherapy for primary pelvic cancers up to 15 th December 2019. We extracted related study characteristics and outcomes. Risk of bias was assessed by the Newcastle-Ottawa Scale. Outcomes were synthesized with random effect models and Manhtel-Haenszel weighting. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational studies in Epidemiology (MOOSE) guidelines were used for reporting this systematic review and meta-analysis. We use GRADE system to assess the quality of main outcome. Results We identified 3958 references after literature searching and eventually 19 studies were selected for meta-analysis. Most studies were cohort studies with moderate risk of bias. Compared with patients treated without radiotherapy, our results showed an increased risk of secondary bladder cancer after radiotherapy for pelvic malignancies (RR 1.75,95% Confidence Interval [CI] 1.50-2.05) with moderate quality of evidence. Similar results were also found in organ-specific analysis of radiation therapy for testicular cancer(RR 2.25,95% CI 1.34-3.78),uterine cancer(RR 2.52,95%CI 1.12-5.67) and prostate cancer(RR 1.64 95%CI 1.39-1.93).Although a varied definitions of latency periods used in different studies, the results showed a consistently increased risk of bladder cancer in all analyzed latency periods, and lag time over 10 years ranked as the highest relative risk(RR 2.98,95%CI 1.88-4.71). When compared with no radiotherapy, EBRT and Any RT significantly increased the risk of second primary bladder cancer (RR 2.08,95%CI 1.67-2.61 and RR 1.77,95%CI 1.49-2.10), but not for BT group (RR 1.58,95%CI 0.98-2.55). Conclusion In conclusion, pelvic radiotherapy was associated with higher relative risk of secondary bladder cancer compared with those without radiotherapy. These findings may help outpatient counseling and early detection of secondary cancer after diagnosis and treatment of first primary cancer. Keywords: Secondary Bladder cancer, Pelvic malignancies, Radiotherapy, Meta-analysis