Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer

• Type of Material: Article
• Authors: Eddie Zhang, Fox Chase Cancer Center; Karen J. Ruth, Fox Chase Cancer Center; Mark K. Buyyounouski, Stanford University; Robert A. Price, Jr., Fox Chase Cancer Center; Robert G. Uzzo, Fox Chase Cancer Center; Mark L. Sobczak, Fox Chase Cancer Center; Alan Pollack, University of Miami; J. Karen Wong, Fox Chase Cancer Center; David Y. T. Chen, Fox Chase Cancer Center; Mark A. Hallman, Fox Chase Cancer Center; Richard E. Greenberg, Fox Chase Cancer Center; Deborah W. Bruner, Emory University; Tahseen Al-Saleem, Fox Chase Cancer Center; Eric M. Horwitz, Fox Chase Cancer Center
• Language: English
• Date: 2023-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.ijrobp.2022.12.008
• Title of Journal or Parent Work: International Journal of Radiation Oncology, Biology, Physics
• Volume: 115
• Issue: 5
• Grant/Funding Information: The Fox Chase Cancer Center institution is supported by the P30 CA006927 NCI Grant.
• Keywords: prostate cancer; IMRT; corporal bodies (CB); erectile function; dose; risk; penile bulb (PB)
• Research Categories: Health Sciences, Oncology

Abstract

Purpose/Objective(s): To prospectively determine if a novel technique to limit the doses delivered to the penile bulb (PB) and corporal bodies (CB) with IMRT preserves erectile function to a greater degree compared to standard IMRT in men with low to intermediate risk prostate cancer. Materials/Methods: From 2003–2012, 116 patients with low to intermediate risk, clinical T1a-T2c prostate adenocarcinoma were enrolled to a single-institution, prospective, single blind, phase III randomized trial. All patients received definitive IMRT to 74–80 Gy in 37–40 fractions. Patients were assigned to receive standard IMRT (s-IMRT) or erectile tissue sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the PB and CB to ≤ 15 Gy and ≤ 7 Gy, respectively. Erectile potency was defined as the ability to attain and maintain penile erection sufficient for satisfactory sexual performance > 50% of the time and was measured using the simplified International Index of Erectile Function (IIEF-5) and PDE5 medication records. Potency preservation outcomes, biochemical failure, overall survival, and acute/late toxicity were compared. Results: 62 patients received ETS-IMRT and 54 received s-IMRT. Treatment arms were balanced with respect to age (median 62 years [range 42–77]), race, smoking status, BMI, baseline AUA score, hypertension, diabetes, and hypercholesterolemia. The majority of patients presented with Gleason 6 disease (ETS-IMRT 79%, s-IMRT 93%, p=0.06), T1c stage (ETS-IMRT 73%, s-IMRT 82%, p=0.32), and pre-treatment PSA < 10 (ETS-IMRT 94%, s-IMRT 93%, p=0.99). Prior to treatment, all patients in both arms reported erectile potency. With a median follow-up time of 6.1 years, 85 patients were eligible for potency preservation analysis. At 24 months after treatment, erectile potency was seen in 52% of patients in the ETS-IMRT arm and 51% of patients in the s-IMRT arm (p=0.95). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (p=0.54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (91.8% vs 90.7%, p=0.77) with a median follow-up of 7.4 years. There were no differences in acute or late GI or GU toxicity. Due to significant baseline PB and CB dose-sparing in the control arm (D90 to PB ≤ 15 Gy was met in 88% of ETS-IMRT patients and 75% of s-IMRT patients; D90 to the CB ≤ 7 Gy was met in 71% of ETS-IMRT patients and 43% of s-IMRT patients), an unplanned per-protocol analysis was performed. No differences in potency preservation or secondary endpoints were seen between patients who exceeded erectile tissue-sparing constraints and those who met constraints. Conclusions: Erectile tissue sparing IMRT that limits dose to the PB and CB is safe and feasible, although there was no significant difference in potency preservation with long-term follow-up.