Effect of chemotherapy on cancer specific mortality in female locally advanced urethral cancer

Objective: To quantify the effect of chemotherapy (CHT) in locally advanced female primary urethral cancer (fPUC). Methods: In the Surveillance, Epidemiology and Ends Results (SEER) database (2000–2021), we identified 295 fPUC patients with locally advanced stage treated with local therapy (surgery or radiation or both) with or without CHT. Multivariable Cox regression models addressed cancer specific mortality free survival (CSM). Sample power analyses were computed. Results: Of 295 fPUC patients, 141 (48%) underwent CHT. CHT rates increased from 40 to 61% (Δ22%) over the study span (2000–2021). Five-year CSM rates of CHT exposed vs. CHT-naïve patients were 58 vs. 43% (Δ15%). In multivariable Cox regression models (age and histology adjusted) CHT independently predicted lower CSM (HR = 0.67, p = 0.027). In squamous cell carcinoma (SCC) subgroup, CHT also independently predicted lower CSM (HR = 0.64, p = 0.01). In urothelial carcinoma (HR = 0.63, p = 0.2) and adenocarcinoma (HR = 0.7, p = 0.7) independent predictor status could not be demonstrated. Small sample sizes in urothelial carcinoma subgroup (UC) and adenocarcinoma subgroup (ADK) undermined the power of the analyses to as low as 48% in UC and 46% in ADK, respectively, versus ideal 80% power. Conclusion: In fPUC patients, CHT independently predicts lower CSM. This effect is generalizable to SCC patients. The same relationship between CHT status and CSM is also operational in UC and ADK subgroups, but limited power undermined confirmation of its’ statistical significance.