A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy

This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL). Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy3 equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy3 equivalent dose in 2Gy fractions). Escalation followed a standard 3 + 3 design with a 6-patient expansion at the maximally tolerated hypofractionated DS. Dose-limiting toxicity was defined as Common Terminology Criteria for Adverse Events v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or G4 gastrointestinal (GI) or genitourinary toxicities thereafter. QOL was assessed longitudinally through 24 months with the Expanded Prostate Cancer Index Composite short form. Between January 2018 and December 2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No dose-limiting toxicities were observed on any DS, and thus, expansion occurred at DS3. The cumulative incidence of G3 GI and genitourinary toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was the most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The biochemical progression-free survival was 91% at both 24 and 60 months. The maximally tolerated hypofractionated DS for hypofractionated, risk volume-adapted PORT was determined to be DS3 (36.4 Gy to the prostate bed and 47.1 Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.