Five-year outcomes of moderately hypofractionated proton therapy incorporating elective pelvic nodal irradiation for high-risk prostate cancer

Purpose: To assess the efficacy of moderately hypofractionated intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for high-risk (HR) or unfavorable intermediate-risk (UIR) prostate cancer (PCa) MATERIALS/METHODS: A prospective study (ClinicalTrials.gov: NCTXXX) of moderately hypofractionated IMPT accrued a target sample size of 56 patients with HR or UIR-PCa . The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 67.5 Gy and 45 Gy, respectively, in 25 daily fractions. All received androgen deprivation therapy (ADT). Its primary objective was late gastrointestinal (GI) and genitourinary (GU) adverse events (AEs), and secondary objectives were a recurrence-free rate (RFR) including freedom from PSA relapse and disease-free survival (DFS) at 5 years. PSA and AEs were evaluated at 3, 6, and 12 months post-IMPT, then every 6 months for 5 years and then yearly thereafter. The actuarial rates of late GI and GU AEs, RFR, and DFS were estimated with Kaplan-Meier method.

Results: Median age was 75 years. Median PSA was 10.5 ng/mL. Fifty-three patients had HR-PCa; 2 had UIR-PCa. Median ADT duration was 18 months. Median follow-up was 62 months. Late grade ≥ 2 and 3 GI AEs at 5 years were 16% and 4%, respectively. Late grade ≥ 2 and 3 GU AEs at 5 years were 41% and 0%, respectively. None had a grade ≥ 4 late AE. At 5 years, RFR and DFS were 90% and 89%, respectively. Seven patients had PCa recurrence, all detected by PSA relapse initially. Three patients died with PSA < 0.1 ng/mL at last follow-up. None died of PCa or treatment-related AEs.

Conclusions: This regimen of moderately hypofractionated IMPT for HR or UIR-PCa yielded encouraging 5-year RFR, DFS, and late AE outcomes. A phase III study is needed to assess any therapeutic gain of IMPT compared with photon-based radiotherapy.