Does neoadjuvant chemotherapy and radical cystectomy in muscle-invasive bladder cancer obliterate survival differences between genders?

Background: The 5-year survival rate in muscle-invasive bladder cancer (MIBC) is approximately 50%, cross over computed tomography (CT) stage in chemo-naive patients. Studies indicate lower survival rates in females when compared to males. The theories that explain the sex disparity are hormonal factors and delayed diagnosis for females. New investigations suggest that neoadjuvant chemotherapy (NAC) might be a possible method for bridging the gender survival gap. The aim of this study was to investigate whether complete treatment with NAC (≥3 cycles) prior to cystectomy reduces the gender gap in survival rates for MIBC and improves the surrogate marker of downstaging.

Methods: A multicenter retrospective cohort from five Swedish urological centers, from 1st January 2005 to 17th July 2023 based on NAC-eligible patients divided in NAC-receiving and non-NAC-receiving subgroups and further divided by sex (males and females). Survival was analyzed based on the Kaplan-Meier method, using log-rank test and adjusted analyses were made with the Cox regression model. Outcome measurements were overall survival (OS), disease-free survival (DFS), and downstaging.

Results: In the analysis of the total cohort (n=412), we could not detect any statistically significant differences in OS between NAC and non-NAC, nor between sexes, in the unadjusted analysis. In the adjusted analysis, we did not observe any significant differences in OS between sexes, either in total or within the NAC subgroups. Further analyzing the NAC group, we could see a significant increased downstaging rate in the NAC group compared to the non-NAC group (P<0.001) which indicates an increased survival in those receiving NAC treatment. There was no relationship between sexes and downstaging (P=0.72). Neither could we see any significant difference in downstaging between males and females in the NAC/non-NAC subgroups (P=0.41 and P=0.92, respectively).

Conclusions: NAC-eligible female and male MIBC patients who underwent radical cystectomy (RC) after at least three cycles of NAC, demonstrated similar OS and DFS. NAC seems to obliterate survival differences between genders in MIBC patients.