The Impact of Squamous Histology on Survival in Patients with Muscle-invasive Bladder Cancer

Background: Bladder cancer is the ninth most common noncutaneous malignancy worldwide, though a fraction (2%-5%) are diagnosed as squamous cell carcinoma (SCC) in the Western world. Current understanding is based on small, single-institution studies and SEER-database reviews with conflicting results. We used the National Cancer Database to explore clinical characteristics and outcomes from a large cohort of invasive bladder SCC.

Methods: We queried the National Cancer Database for diagnoses of urothelial carcinoma (UC) or SCC using International Classification of Disease-O-3 morphologic codes from cases reported between 2004 and 2015. Primary outcome was overall survival in cT2-4N0M0 bladder cancer. Statistical analysis performed using chi-squared test, Kaplan-Meier survival, binomial logistic regression, and Cox proportional hazards.

Results: The final cohort included 394,979 bladder cancer patients, of which 4,783 (1.2%) were classified as SCC histology. In comparison to UC, patients with SCC were more likely female (49% vs. 24%; P < 0.01) and African American (11% vs. 5%; P < 0.01). Patients with SCC presented at a higher stage than UC with muscle-invasive bladder cancer (MIBC) present at diagnosis in 70% vs. 19%. On multivariate analysis, SCC independently predicted poorer prognosis (hazard-ratio [HR] 1.79, P < 0.01) when controlling for patient characteristics and treatment modality. Unlike UC, there was no benefit with the use of NAC over radical cystectomy alone (HR 0.93, P = 0.69) for patients with SCC.

Conclusions: Invasive SCC of the bladder carries a worse prognosis as compared to UC histology, both overall and on a stage-for-stage basis. As opposed to UC, we did not observe a survival benefit for NAC among SCC patients treated with cystectomy.