Comparative Effectiveness of Treatment Strategies for Squamous Cell Carcinoma of the Bladder

While there is established evidence supporting the use of radical cystectomy (RC) and perioperative chemotherapy for muscle-invasive urothelial carcinoma of the bladder, such evidence does not exist for squamous cell carcinoma.

We present the largest study to date of patients with squamous cell carcinoma and compare the effectiveness of possible treatment regimens for overall survival.

The National Cancer Data Base was queried for cases of localized, muscle-invasive pure squamous cell bladder cancer, classified as clinical stage T2/3N0M0. Permutations of surgery (RC), chemotherapy, and external beam radiation were selected.

A multinomial propensity score method was used to create treatment weights based on clinical characteristics predicting the probability of treatment receipt. These were then applied in weighted Cox proportional hazards models to assess the comparative effectiveness of treatments for overall survival, adjusting for age, TNM clinical stage, Charlson comorbidity index, race, sex, and facility and county level variables.

A total of 828 cases were included, comprising 465 RC alone, 53 neoadjuvant chemotherapy+RC, 48 RC+adjuvant chemotherapy, 72 chemotherapy alone, 88 radiation alone, and 102 chemoradiation cases. On weighted regression, RC treatment with or without perioperative chemotherapy was associated with significantly better overall survival compared to the other treatment modalities; chemotherapy alone, radiation alone, and chemoradiation were associated with a hazard ratio (HR) of death of 2.43 (95% confidence interval [CI] 1.65-3.59), 4.78 (95% CI 3.33-6.86), and 1.61 (95% CI 1.16-2.25), respectively, compared to RC alone (all p<0.005). A combination of RC and neoadjuvant chemotherapy was comparable to RC alone, with HR of death 1.33 (95% CI 0.89-1.98). The combination of RC and adjuvant chemotherapy was also similar to RC alone (HR 1.11, 95% CI 0.66-1.85). These findings are limited by small numbers and the retrospective nature of the study.

RC with or without perioperative chemotherapy should be considered an upfront therapy for squamous cell carcinoma of the bladder.

Using a national database, we compared treatments for muscle-invasive squamous cell bladder cancer. Patients undergoing radical cystectomy with or without chemotherapy had longer survival. Radical cystectomy with or without chemotherapy should be the standard of care for this disease.