Characteristics of Radiation-Associated Bladder Cancer Compared To Primary Bladder Cancer

Abstract

Radiation-associated muscle-invasive bladder cancer (RA-MIBC) has been suggested to represent a more aggressive disease variant compared to primary (non-radiation associated) MIBC. We sought to characterize the presentation, patterns of care, and outcomes of RA-MIBC compared to primary MIBC. We identified 60,117 patients diagnosed with non-metastatic or metastatic MIBC between 1988 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database and stratified patients based on whether radiation had been administered to a pelvic primary prior to the development of bladder cancer. We used logistic regression to compare rates of chemotherapy, surgery, or radiation for patients with RA-MIBC compared to primary MIBC. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC. There were 1,093 patients with RA-MIBC and 59,024 patients with primary MIBC. Patients with RA-MIBC were older compared to patients with primary MIBC (mean age 77.4 years vs 72.4 years, p < 0.001) and more likely to be male (86.8% vs 73.3%, p<0.001). RA-MIBCs were more likely to be high-grade (57.5% vs 47.6%, p<0.001) more likely to have T4 disease at diagnosis (21.0% vs 17.3%, p<0.001), and less likely to be node-positive (4.2% vs 8.1%, p < 0.001). In terms of treatment, primary MIBC patients with non-metastatic disease were more likely to undergo radiation (14.0% vs 3.1%, p<0.001) as well as radiation with cystectomy (1.9% vs 0.8%, p<0.001) compared to those with RA-MIBC. Median survival was significantly shorter for patients with RA-MIBC (13 mo. vs 19 mo.; p<0.001). RA-MIBCs tend to present with higher grade and higher stage disease and are less likely to receive curative treatment. Even when adjusting for stage, grade, and receipt of treatment, patients with RA-MIBC have worse survival compared to those with primary MIBC. These findings raise the possibility that RA-MIBC represents a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand biological differences between RA-MIBC and primary MIBC and develop improved therapeutics for radiation-associated cancers.