Rates of acute GI and GU toxicities with dose-escalated intensity modulated proton therapy (IMPT) for the treatment of node-positive prostate cancer.

380 Background: Node-positive prostate cancer (PCa) poses a unique treatment challenge since bowel radiation tolerance often limits the delivery of doses of 60-70Gy or more required to control gross nodal disease. IMPT is a novel therapeutic option which utilizes beam stopping properties to achieve dose sparing of normal organs with the ability to dose escalate (DE) with potentially greater safety. However, the safety of DE-IMPT in node positive PCa has not been well described. Methods: Data were reviewed for consecutive patients treated between 9/2018-4/2024 with DE-IMPT for radiographically detected node-positive PCa. Treatment to the prostate and seminal vesicles consisted of 78Gy/39fractions; elective nodal regions received 46-48.6Gy in 1.8-2Gy/fraction, as part of whole pelvis treatment, while positive nodes were DE to a mean equivalent dose at 2 Gy/fraction (EQD2) dose of 66Gy (54-77.1Gy) in 1.8-2.5Gy/fraction, based on respecting predefined surrounding organs at risk (OAR) tolerances. Acute toxicities were assessed at baseline, weekly during treatment, and up to 3 months post-IMPT using Common Terminology Criteria for Adverse Events (CTCAE version 5). Results: The study included 58 patients presenting with a mean of 3 positive nodes (1-12). Median follow up was 19.5 months (3-67 months). Median age was 73 years (49-86). Majority were high-risk: Gleason 8-10 (67.2%), T3a-b (50%), PSA > 20 (44.8%). Median prostate gland volume was 52cc (19-157). All pts received androgen deprivation therapy (ADT) with 97% completing at least 6 months; Androgen receptor pathway inhibitors were added in 26 pts (45%). Overall mean rectal V70, V60 and V50 were 6.7%, 11.2% and 16.5% while mean bladder V70, V60 and V50 were 12%, 17.3% and 24%, respectively. Mean small bowel dose to 1 cc volume D 1cc was 50.7Gy (45.6-57Gy), while mean Dmax point dose to 0.03cc was 52.2Gy (47.8-61.8). Worst acute Genitourinary (GU) toxicities Grade 0 and 1 were 1.7% and 12%, respectively. During treatment, 18/58 patients (31%) were started on Alpha-blockers for increased urinary frequency, retention and urgency, consistent with GU Grade 2 toxicity of which 7(39%) had discontinued medication by 3 months post-treatment. Before treatment, 32/58 (55.1%) were already on Alpha-blockers. There were no GU Grade ≥ 3 toxicities observed. Acute gastrointestinal (GI) Grade 0 and 1 were 43.1% and 53.5%, respectively. Grade 2 GI toxicities were observed in 2 (3.4%) patients consisting of diarrhea and proctitis. One patient (1.7%) developed transient Grade 3 enteritis. Conclusions: This contemporary series demonstrates that DE-IMPT is a safe treatment option for node-positive PCa with acceptable rates of acute grade 1 or 2 toxicity. Acute grade 3 toxicity was rare, occurring in only one patient in this cohort.