Phase I/IIa trial of androgen deprivation therapy, external beam radiotherapy, and stereotactic body radiotherapy boost for high-risk prostate cancer (ADEBAR)

Abstract

Background To evaluate the clinical outcomes of combination of androgen deprivation therapy (ADT), whole pelvic radiotherapy (WPRT), and stereotactic body radiotherapy (SBRT) boost in high-risk prostate cancer patients. Methods This prospective phase I/IIa study was conducted between 2016 and 2017. Following WPRT of 44 Gy in 20 fractions, patients were randomized to two boost doses, 18 Gy and 21 Gy, in 3 fractions using the Cyberknife system. Primary endpoints were incidences of acute toxicities and short-term biochemical recurrence-free survival (BCRFS). Secondary endpoints included late toxicities and short-term clinical progression-free survival (CPFS). Results A total of 26 patients were enrolled. Twelve patients received a boost dose of 18 Gy, and the rest received 21 Gy. The Median follow-up duration was 35 months. There were no grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicities. Sixty-one and 4% of patients experienced grade 1–2 acute GU and GI toxicities, respectively. There were 12% late grade 1–2 GU toxicities and 8% late grade 1–2 GI toxicities. Patient-reported outcomes of urinary symptoms were aggravated after WPRT and SBRT boost. However, they resolved at 1 month and returned to the baseline level at 4 months. Three-year BCRFS was 88.1%, and CPFS was 92.3%. Conclusions The present study protocol demonstrated that the combination of ADT, WPRT, and SBRT boosts for high-risk prostate cancer is safe and feasible, and may reduce total treatment time to 5 weeks. Boost dose of 21 Gy in 3 fractions seems appropriate. Trial registration ClinicalTrials.gov, ID; NCT03322020 - Retrospectively registered on 26 October 2017.

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation

“…The cumulative incidence of GU and GI grade 2 toxicity was quite moderate, measured at 1.4% and 9.3%, respectively, and the 3-year biochemical relapse-free survival was nearly 90%. The second study from Korea explores an SBRT total boost dose question ( 25 ). Kim et al.…”

A Multicenter Phase 2 Study of Ultrahypofractionated Stereotactic Boost After External Beam Radiotherapy in Intermediate-risk Prostate Carcinoma: A Very Long-term Analysis of the CKNO-PRO Trial

“…An SBRT boost could be a noninvasive alternative to a BT boost after EBRT in intermediate- and high-risk prostate cancer. An SBRT boost has been evaluated in a few early-phase prospective studies, with a short follow-up period of <5 yr [9] , [10] , [11] , except for one [8] . In three of the five series, including ours, a rectal spacer was not used [8] , [9] .…”

“…An SBRT boost has been evaluated in a few early-phase prospective studies, with a short follow-up period of <5 yr [9] , [10] , [11] , except for one [8] . In three of the five series, including ours, a rectal spacer was not used [8] , [9] . The SBRT boost was delivered in two to three fractions, except in one phase 1 trial [8] .…”

“…Despite higher doses per fraction, in patients treated exclusively by SBRT, the toxicity profile has been shown to be comparable with that with conventionally fractionated radiotherapy [6] , [7] . SBRT has been evaluated as a boost after or before EBRT in very few small prospective trials with short follow-up periods [8] , [9] , [10] , [11] . A 5-yr analysis reported favorable gastrointestinal (GI) and genitourinary (GU) toxicity profiles and RFS results [12] .…”

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer

“…Posttreatment biopsy and comparative clinical trial data suggest room for further disease control improvement at doses >40 Gy in 5 fractions, with limited toxicity data (13,14). Brachytherapy boost treatments have shown that escalating the biological dose of RT can improve prostate cancer outcomes; however, this modality consists of invasive treatments associated with increased toxicity and technical requirements (26)(27)(28). SAbR offers a promising and non-invasive alternative to brachytherapy for improving localized PCa outcomes.…”