Patients With Muscle-Invasive Squamous Cell Carcinoma Of The Bladder Have Worse Survival Compared To Other Histologies When Undergoing Definitive Radiation Therapy

Although transitional cell carcinoma (TCC) is the most common histology in muscle-invasive bladder cancer (MIBC), multiple other histologies can also occur in the bladder. These patients are typically treated similarly to those with TCC, but given the rarity of these other histologies in the U.S., there are limited studies comparing the survival outcomes between histologies, and prior prospective trials have few patients with non-TCC histologies. The objective of our study was to use the National Cancer Database (NCDB) to explore differences in survival between the histologies when treated with radiotherapy. We conducted a retrospective cohort study of patients with cT2-4 N0-3 M0 MIBC in the NCDB treated with curative radiotherapy (≥60 Gy) with or without concurrent chemotherapy (CC). Histologies were identified as TCC, squamous cell carcinoma (SCC), small cell carcinoma (SmC) and sarcoma. Chi-square tests were used to determine differences in clinical characteristics between each histology group. Overall survival was estimated using the Kaplan-Meier method and univariate analysis (UVA) was conducted using the Log Rank test to identify the impact of histology and other clinical and sociodemographic characteristics on overall survival (OS). Multivariable analysis (MVA) was conducted using the Cox Proportional Hazards model, and included all covariates with p-value < 0.1 on UVA. Our cohort consisted of 4,056 patients (TCC = 3,833, SCC = 127, SmC = 83, sarcoma = 13). Median follow-up was 21 months (interquartile range 11.5-43.1 months). Compared to TCC, the other histologies were more likely to be node positive (7.57% for TCC, 14.96% for SCC, 9.64% for SmC, and 15.38% for sarcoma, p=0.014). SCC patients were the most likely to have T3/T4 disease (24.86% for TCC, 44.88% for SCC, 20.48% for SmC, and 15.38% for sarcoma, p<0.001). Sarcoma patients had the highest proportion with charlson-deyo comorbidity score (8.92% for TCC, 7.87% for SCC, 1.20% for SmC, and 15.38% for sarcoma, p=0.032). Two year OS was 50%. This was 51% for TCC, 26% for SCC, 47% for SmC and 46% for sarcoma. On UVA, SCC histology was associated with OS (p<0.001), as were increasing t-stage (p<0.001), n-stage (p<0.001), age (p<0.001), charlson-deyo comorbidity score (p<0.001). Census region (p=0.028) and lack of CC (p<0.001) also had worse OS. On MVA, SCC histology was associated with worse OS compared to TCC (hazard ratio 1.99 (1.63-2.42); p<0.001), while the others had similar OS compared to TCC (p=0.545 for SmC, p=0.424 for sarcoma). Increasing age (p<0.001), charlson-deyo comorbidity score (p<0.001), T-stage (p<0.001), N-stage (p<0.001), and lack of CC (p<0.001) were also associated with worse OS. Independent of extent of disease and comorbidity, patients with SCC have worse survival compared to other histologies when treated with curative radiotherapy. Further investigation into novel approaches in this cohort of patients with a poor prognosis is necessary.