A Phase I Trial of Image-Guided, Risk-Volume-Adapted Post-Prostatectomy Radiotherapy.

Abstract

Purpose: This is a phase I trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk-volume-adapted, hypofractionated, post-operative radiotherapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression free survival (bPFS) and quality of life (QOL).

Methods: Patients were treated with one of 3 isoeffective dose schedules (DS1: 20 fractions, DS2: 15 fractions, DS3: 10 fractions) that escalated dose to the imaging-defined local recurrence (73Gy₃ EQD2) and de-escalated dose to the remainder of the prostate bed (48Gy₃ EQD2). Escalation followed a standard 3+3 design with a 6-patient expansion at the maximally tolerated hypofractionated dose schedule (MTHDS). Dose limiting toxicity (DLT) was defined as CTCAE v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or grade 4 gastrointestinal (GI) or genitourinary (GU) toxicities thereafter. QOL was assessed longitudinally through 24 months with the EPIC-26.

Results: Between 01/2018 and 12/2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No DLTs were observed on any DS, and, thus, expansion occurred at DS3. The cumulative incidence of G3 GI and GU toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was 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 bPFS was 91% at both 24- and 60-months.

Conclusions: The maximally tolerated hypofractionated dose schedule for hypofractionated, risk-volume-adapted PORT was determined to be DS3 (36.4Gy to the prostate bed and 47.1Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.