Comparison of Conventional Versus Hyperfractionated Chemoradiation for Bladder Preservation Treatment of Muscle Invasive Bladder Cancer in the National Cancer Database

Abstract

It is unclear whether hyperfractionated (HF) chemoradiation therapy (CRT) results in a different overall survival (OS) outcomes compared to conventional daily fractionated CRT for bladder preservation treatment of muscle invasive bladder cancer. We compared these two treatment strategies using data from the National Cancer Database (NCDB). Using data from the NCDB between 2004 and 2013, we identified 3010 patients with bladder cancer treated with CRT for bladder preservation. Patients with stage T2-T4a transitional cell or squamous cell carcinoma of the bladder who received trans-urethral resection of bladder tumor (TURBT) and CRT were included. Average number of fractions delivered per week was calculated based on the total number of fractions of radiation, and the time interval between the first and last fraction in the NCBD. Conventional CRT was defined as five or fewer fractions per week, on average, over the course of CRT, and HF CRT was defined as more than five fractions a week on average. We compared the OS outcomes between the conventional CRT and HF CRT using the Kaplan-Meier method with log-rank statistics, and Cox univariate and multivariate analysis. Of the 3010 patients analyzed, 2822 (93.8%) received conventional CRT and 188 (6.2%) received HF CRT. The median age was 78 (range, 37-90), and 2208 (73.4%) were males and 802 (26.6%) were females. The median follow up time was 42.2 months (range, 2.5-143 months) for surviving patients. The pathology was transitional cell carcinoma in 2,919 (97%) and squamous cell carcinoma in 91 (3%). Distribution of stages was 2,360 (78.4%) for T2, 371 (12.3%) for T3, and 279 (9.3%) for T4a. 5-year OS in patients treated with standard fractionation was 28.9% vs. HF treatment with 22.7% (p=0.86). HF RT was associated with a similar hazard for death when compared to the standard radiation, which was 1.02 (95% CI 0.853-1.208, p=0.863). Several variables were associated with improved OS on univariate analysis including: age, Charlson/Deyo comorbidity score, histology, T stage, N stage and total dose. After adjusting for these factors in a step-wise model, standard fractionation vs. HF was not significant (p=0.396). Additionally, HF RT was not associated with improved OS compared to standard fractionated RT in subsets including patients with: stage T2 (p=0.507), T3 (p=0.331), and T4a (p=0.208). HF CRT resulted in similar overall survival when compared to standard fractionated CRT in patients with T2-T4a bladder cancer receiving bladder preservation therapy.