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

Abstract

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. From 2003-2012, 116 patients with low to intermediate risk, clinical T1a-T2c prostate adenocarcinoma were enrolled to a single-institution, prospective, 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. Patients were blinded to the treatment arm. Erectile potency was defined as the ability to attain and maintain penile erection sufficient for satisfactory sexual performance >50% of the time and was assessed using the simplified International Index of Erectile Function (IIEF-5) and PDE5 inhibitor medication records. Comparison of potency preservation outcomes was conducted at various time points in an intention-to-treat analysis using two-sample, two-sided chi-square tests. Biochemical failure and late toxicities were compared using Kaplan-Meier survival analysis and the log-rank test. Sixty-two 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. 4 patients (6%) on the ETS-IMRT arm and 1 patient (2%) on the s-IMRT arm reported PDE5 inhibitor use prior to treatment (P = 1.00). D90 to the 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. With a median follow-up time of 6.1 years, 85 patients were eligible for potency preservation analysis. At 19-30 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 52% of ETS-IMRT patients and 44% of s-IMRT patients (P = 0.49). 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. 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 at 6 years.