3241 - Outcomes with Salvage Dose-Escalated Intensity Modulated Proton Therapy in Node-Positive Recurrence after Prostatectomy

Purpose/Objective(s): Intensity modulated proton therapy (IMPT) has dosimetric advantages allowing for high dose radiation near organs at risk. We hypothesize that IMPT may permit safe dose escalation in prostate cancer (PCa) patients with node positive (N+) recurrences after prostatectomy. Here we examine initial outcomes with dose escalated IMPT (DE-IMPT) in a cohort of salvage N+ PCa patients.

Materials/Methods: We retrospectively analyzed consecutive PCa patients treated with DE-IMPT for image-detected N+ relapse after prostatectomy between 2017 and 2024. Node positivity was determined using size criteria (>1 cm) or PSMA avidity. Biochemical control was assessed with post-treatment PSA levels. Patient characteristics and outcomes were evaluated using the Kaplan–Meier method, Cox proportional hazards models, and logistic regression.

Results: A total of 36 patients were analyzed with a median age of 69 years (range, 52–84 years). Most patients had 1 N+ (61.1%) with the remainder having 2–5 N+. Target dose ranges included 66-74 Gy / 33-37 fractions to the prostate bed and 45–48.6 Gy / 23-27 fractions to elective pelvic nodes. N+ targets received a median equivalent dose at 2Gy/fraction (EQD2) of 66Gy (range, 54-73.5 Gy) in 1.8-2.5Gy/fraction. The majority of patients were pT2-3 (97.3%), N0 (75.0%), and R0 (66.7%) at prostatectomy. Most patients harbored clinical grade group 2 (22.2%), group 3 (41.7%) or group 5 (30.6%) disease. Median pre-radiation PSA at relapse was 0.65 ng/mL (range, 0.01-21.5 ng/mL). All patients received androgen deprivation therapy concurrent with DE-IMPT. Median follow-up was 22.7 months (range, 1.1-64.3 months). There were no acute or late grade 2+ gastrointestinal (GI) toxicities. Grade 2 genitourinary (GU) toxicity rates were 16% for both acute and late events, respectively. Only one patient (3%) experienced acute grade 3 GU toxicity with no cases of late grade 3+ events. The overall median biochemical progression free survival (bPFS) was 50.2 months. Median bPFS was 50.1 months in patients with multiple N+, but the median bPFS timepoint was not reached in patients with only one N+. There was no association between dose levels to N+ targets and bPFS (p=0.489).

Conclusion: IMPT permits safe dose escalation with low rates of grade 2+ GI and GU toxicities. Increased N+ tumor burden is associated with higher risk of progression, suggesting the need for treatment intensification in this subgroup. Our study did not show an association with nodal dose-escalation and bPFS, likely due to the small sample size and limited follow-up (median 22.7 months) with few biochemical failure events. Nevertheless, the current study provides initial safety data for future prospective trials with sufficient power to analyze bPFS benefits from N+ dose escalation.