Impact of Gender on Chemotherapeutic Response and Oncologic Outcomes in Patients Treated With Radical Cystectomy and Perioperative Chemotherapy for Bladder Cancer: A Systematic Review and Meta-Analysis

Female patients with bladder cancer (BCa) have had more advanced disease than their male counterparts at diagnosis and have experienced worse oncologic outcomes. However, the effect of gender on the chemotherapeutic response and oncologic outcomes after radical cystectomy (RC) and perioperative chemotherapy remains to be elucidated. We performed a systematic literature search to identify eligible studies that had investigated the effect of gender on the chemotherapeutic response and oncologic outcomes after RC and perioperative chemotherapy. We identified 15 studies reported from 2008 to 2019. For the patients who had received neoadjuvant chemotherapy (NAC), female gender was not associated with a complete response (pooled odds ratio [OR], 0.94; 95% confidence interval [CI], 0.69-1.26) nor a complete or partial response (pooled OR, 0.96; 95% CI, 0.73-1.27). In addition, women experienced had less upstaging (pooled OR, 0.3; 95% CI, 0.14-0.68) at RC compared with their male counterparts. Moreover, female patients who had undergone RC and NAC were likely to have better disease recurrence and cancer-specific mortality rates than were the male patients (pooled hazard ratio [HR], 0.66 and 95% CI, 0.44-0.98; and pooled HR, 0.49 and 95% CI, 0.29-0.81, respectively). For the patients who had undergone adjuvant chemotherapy, female gender was not associated with overall mortality (pooled HR, 1.15; 95% CI, 0.7-1.89), disease recurrence (pooled HR, 0.95; 95% CI, 0.74-1.23), or cancer-specific mortality (pooled HR, 1.07; 95% CI, 0.81-1.43). Female patients with BCa seem to benefit more from NAC than do their male counterparts. This potential differential sensitivity of female BCa to cisplatin-based combination chemotherapy might help close the gender gap in BCa, suggesting that gender could be a biomarker to help select the best systemic therapy for patients with advanced BCa.