Real-World Toxicity of Conventional Versus Hypofractionated Definitive Prostate Radiotherapy across a Large, Diverse, Academic and Community-Based Enterprise.

Abstract

Over the past 10-15 years there has been increasing adoption of moderate hypofractionation (HF) for definitive prostate radiotherapy as compared to conventional fractionation (CF). Based on several randomized trials hypofractionation results in equivalent treatment efficacy with similar rates of long-term toxicity. However, some studies suggest higher acute GI toxicity with moderate hypofractionation. We sought to compare the rates of toxicity between these two groups across our enterprise including 16 community-based practices and one academic NCI-designated comprehensive cancer center. We retrospectively extracted radiation treatment intent from our network-wide clinical pathways for patients diagnosed with prostate cancer between 3/2019 and 10/2022. Patients treated after prostatectomy and those treated with brachytherapy or SBRT were excluded. For the remaining 1529 patients treated with either conventional fractionation or moderate hypofractionation, we identified and merged physician-graded toxicity data using CTCAE version 5.0 recorded in their electronic medical record at each weekly on-treatment visit and follow-up. A total of 1051 patients had toxicity data available. Rates of toxicities were then compared between the cohort of patients who received CF and those who HF using the Chi-square test. Of the 1051 patients, 450 (43%) received CF and 601 (57%) received HF. These patients were treated by 40 different radiation oncologists (median patients per physician = 18, interquartile range = 7-35). Median age in the CF and HF cohorts was 71 (IQR: 66-76) and 71 (IQR: 66-77; p = 0.51), respectively. The CF cohort had more patients with Gleason 8+ disease (39% vs 19%; p<0.01), PSA >20 (26% vs 11%; p<0.01), or T3a+ (18% vs 8%; p<0.01). Rates of any grade 2+ toxicity were significantly higher in patients who received HF at 45.8% vs 39.6% for those treated with CF (p = 0.04). However, the respective rates of any grade 3+ toxicity were no different at 2.0% vs. 1.8% (p = 0.80). The difference in grade 2 toxicities appeared to be primarily driven by the rates of urinary frequency at 27.1% vs. 17.8% (p<0.01) and prostatic obstruction 14.8% vs. 10.2%, p = 0.03). Rates of grade 2 diarrhea were worse with MF at 5.3% vs. 2.8% for CF (p = 0.04). There were no significant differences between HF and CF in the rates of grade 2 dysuria (6% vs 5.2%), urinary urgency (6.5% vs. 4.2%), proctitis (3.0% vs. 3.6%), urinary incontinence (0.5% vs. 1.3%), rectal bleeding (0.3% vs. 0%), hematuria (0% vs. 0.4%), and fatigue (14.1% vs. 15.1%). In this large network-wide analysis, toxicity was slightly increased among patients with prostate cancer treated with HF compared to CF, consistent with published randomized data. However, the increased toxicity appeared to be primarily GU rather than GI. This study demonstrates the feasibility of analyzing impacts of treatment decisions on a large scale using real-world data through an integrated network of practices.