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Sex-specific differences in the quality of treatment of muscle-invasive bladder cancer do not explain the overall survival discrepancy

  • Marieke J. Krimphove,
  • Julie Szymaniak,
  • Maya Marchesea,
  • Karl H. Tully,
  • David D’Andrea,
  • Matthew Mossanen,
  • Stuart R. Lipsitz,
  • Kerry Kilbridge,
  • Adam S. Kibel,
  • Luis A. Kluth,
  • Shahrokh F. Shariat,
  • Quoc-Dien Trinh





Background

While bladder cancer is less common among women, female sex is associated with worse oncological outcomes.

Objective

To evaluate sex-specific differences in initial presentation and treatment patterns of muscle-invasive bladder cancer.

Design, setting, and participants

A retrospective study using the National Cancer Database to identify individuals diagnosed with muscle-invasive bladder cancer (cT2-T4aN0M0) between 2004 and 2013.

Outcome measurements and statistical analysis

Multivariable logistic regression and negative binomial regression with Bonferroni correction were used to investigate seven treatment measures: care at a high-volume facility, receipt of definitive therapy, delayed treatment, receipt of neoadjuvant or adjuvant chemotherapy, receipt of pelvic lymph node dissection, and number of lymph nodes removed. The secondary outcome was overall survival.

Results and limitations

We identified 27 525 patients, 27.4% of whom were females. Females were diagnosed significantly more often with nonurothelial carcinoma (15.1% vs 9.9%, p < 0.001), with squamous carcinoma being the most prevalent variant (46.9%). After Bonferroni correction, there was no difference in six out of seven treatment quality measures. Females were significantly less likely to experience delayed treatment (odds ratio 0.89, 95% confidence interval [CI] 0.84–0.93, p < 0.001). Females had significantly worse overall survival compared with males (hazard ratio 1.04, 95% CI 1.00–1.07, p = 0.030). Limitations arise from the retrospective design of the study.

Conclusions

Despite little difference in treatment quality measures, female sex is associated with worse overall survival among individuals with muscle-invasive bladder cancer. Our findings suggest that differences in treatment patterns are unlikely to explain the differences in overall survival. Future initiatives should focus on root causes for gender-specific differences in pathological staging and features at diagnosis.

Patient summary

In this study, we did not find differences in the treatment of bladder cancer between men and women that could readily explain why women diagnosed with this disease are more likely to die.


Commentary by Dr. Evanguelos Xylinas

In the June edition of European Urology Focus, Krimphove and colleagues have investigated the potential negative effect of female gender on the oncological outcomes of patients treated for bladder cancer. While bladder cancer is less common among women, female gender has been long associated with worse oncological outcomes. The main hypotheses on top of potential different (more aggressive) biology, have been differences in initial presentation and treatment patterns leading to under- (suboptimal) or delayed treatment in female patients.

The authors performed a retrospective study including 27525 patients (27.4% of whom were females) using the National Cancer Database in order to identify patients diagnosed with muscle-invasive bladder cancer (cT2-T4aN0M0) between 2004 and 2013. They used a multivariable logistic regression and negative binomial regression with Bonferroni correction, to investigate seven treatment measures: care at a high-volume facility, receipt of definitive therapy, delayed treatment, receipt of neoadjuvant or adjuvant chemotherapy, receipt of pelvic lymph node dissection, and number of lymph nodes removed. The secondary outcome was overall survival.

They found that female patients were more likely to be diagnosed with non-urothelial carcinoma (15.1% vs 9.9%, p<0.001), with squamous carcinoma being the most prevalent variant (46.9%). After Bonferroni correction, there was no difference in six out of seven treatment quality measures between male and female patients. Moreover, female patients were significantly less likely to experience delayed treatment (odds ratio 0.89, 95% confidence interval [CI] 0.84-0.93, p<0.001). Finally, the authors confirmed using the National Cancer Database that female patients had significantly worse overall survival outcomes (hazard ratio 1.04, 95% CI 1.00-1.07, p=0.030).

These findings suggest that differences in treatment patterns are unlikely to explain the differences in overall survival of female patients with muscle-invasive bladder cancer. Future initiatives should focus on the biology of the disease as well as on initial presentation management and awareness among female patients.