Trends and Predictors of Hypofractionated and Intensity-Modulated Radiotherapy for Organ Preservation in Bladder Cancer

This National Cancer Database study of bladder cancer patients treated with definitive (chemo) radiotherapy uncovered significant under-utilization of hypofractionated RT (HFRT). Furthermore, chemotherapy was significantly underused with HFRT compared to patients receiving conventional fractionation. Use of both intensitymodulated RT (IMRT) and HFRT increased over time. IMRT was associated with similar or modestly increased survival, particularly in patients receiving HFRT. Introduction: : Use of hypofractionated radiation (HFRT) and intensity-modulated radiation (IMRT) for organ preservation in bladder cancer is controversial and highly variable. We investigated practice patterns, trends, and predictors of HFRT and IMRT. Patients and Methods: : The National Cancer Database was queried for patients with muscleinvasive, non-metastatic urothelial bladder cancer, treated with definitive (chemo)radiotherapy between 2004 and 2017. HFRT was defined as 50 to 60 Gy at 2 Gy/fraction. Multivariable logistic regression was used to identify predictors of receiving HFRT or IMRT. Multivariable Cox regression was used to model overall survival (OS), adjusting for potential confounders such as age, comorbidity, and chemotherapy. Results: : Of 5132 patients identified, 490 (9.5%) received HFRT, and only 334 (6.5%) received >= 2.5 Gy/fraction. HFRT patients were significantly older, less fit, and less likely to receive chemotherapy relative to CFRT, even after controlling for age and comorbidity (adjusted odds ratio 0.36, 95% confidence interval [CI] 0.29-0.45, P < .0001). Utilization of HFRT and IMRT increased over time ( P < .0001), reaching 22.5% and 47.7%, respectively, by 2017. Among patients treated with CFRT, OS was similar with or without IMRT ( P = .46). Among patients treated with HFRT, IMRT was associated with increased survival (3-year OS 35% vs. 24%, P = .03), which persisted in multivariable analysis (adjusted hazard ratio 0.71, 95% CI 0.52-0.98, P = .04). Conclusion: : HFRT is largely underutilized, being primarily reserved for older, frailer patients. Chemotherapy is significantly underused with HFRT relative to CFRT. IMRT is used frequently and was associated with equivalent or modestly increased overall survival.