Thursday, July 11, 202410:30 AM - 11:30 AMPPP01 Presentation Time: 10:30 AM

Purpose

A high radiation dose (≥ 75 Gy EQD2) is required to achieve tumor control in intermediate / high-risk prostate cancer (PCa). Brachytherapy (BT) provides a steep dose gradient, resulting in a higher dose to the tumor while minimizing dose to surrounding organs. Therefore, a combination of external beam radiotherapy (EBRT) and a BT boost may potentially result in less gastrointestinal (GI) and genitourinary (GU) toxicity. This multicenter, randomized trial was designed to compare the toxicity of EBRT alone with that of EBRT plus a BT boost. Here we present the primary endpoint: the 3 years late GI and GU toxicity. Overall survival (OS), biochemical disease-free survival (bDFS) and relapse-free survival (RFS) were analyzed as secondary endpoints.

Materials and Methods

Patients with PCa, stage T1c-T3a, N0, M0, PSA ≤ 60 ug/l and Gleason ≤ 8, were randomized to: EBRT alone (35 × 2.2 Gy) or EBRT (20 × 2.2 Gy) + BT boost (HDR: 1 × 13 Gy or PDR: 24 × 1.27 Gy, 2.2 hour interval). Both arms received an EQD2 of 79 Gy. EBRT was given using intensity modulated radiotherapy. The toxicity was assessed with the RTOG Late Radiation Morbidity Scoring criteria from both physicians’ records (clinical record form) and patients’ self-assessment questionnaires, at baseline, every 6 months for the first 3 years, and at 4 and 5 years post treatment. For both GI and GU toxicity, the highest score and the earliest date corresponding to the occurrence of grade ≥2 toxicity was registered for analysis. For the cumulative incidence of grade ≥ 2 late GI / GU toxicity, a competing risk regression analysis was performed considering death without toxicity as the competing event. First a univariate regression analysis was performed, followed by a multivariate regression analysis with adjustment for significant univariable prognostic factors. With age, PSA, Gleason, T-stage, risk classification, smoking, urinary flow, hormonal therapy, diabetes, abdominal surgery, GI comorbidity, prostate volume and overall GI/GU at baseline considered as candidate prognostic factors. OS, bDFS and RFS were assessed from randomization using the Kaplan-Meier method and univariate / multivariate Cox regression.

Results

From March 2013 to March 2019, 196 evaluable patients were enrolled. Baseline patient and tumor characteristics as well as baseline toxicity were well balanced between arms. The 3-year cumulative incidence of grade ≥ 2 GI toxicity (Fig. 1a) was 22% (EBRT+BT) vs 31% (EBRT), not statistically different in univariate (HR 0.67; 95% CI 0.41 - 1.12; p=0.129). Since no factor seem to have prognostic value for grade ≥ 2 GI toxicity based on the univariate analysis, no multivariate analysis was conducted. The 3-year cumulative incidence of grade ≥ 2 GU toxicity (Fig. 1b) was 43% (EBRT+BT) vs 29% (EBRT), not statistically different in univariate (HR 1.49; 95% CI 0.98 - 2.27; p=0.064) nor multivariate analysis adjusted for diabetes mellitus (yes/no) (HR 1.44; 95% CI 0.94 - 2.20; p=0.090). At 3 years, OS was 95% vs 98%, bDFS 97% vs 98% and RFS 97% vs 97%, in EBRT+BT vs EBRT, respectively. No significant differences between the arms were found.

Conclusions

In this multicenter, randomized trial that investigated the added value of a BT boost compared to EBRT alone, the observed decrease in grade ≥ 2 late GI and increase in grade ≥ 2 late GU toxicity did not reach statistical significance.