Phase 1-2 trial of dose-escalated focal salvage HDR brachytherapy and genomic classifier risk stratification in radiorecurrent prostate cancer

Prospective data on the management of intraprostatic radiorecurrence (IPR) after definitive radiotherapy (RT) and use of genomic classifiers (GC) in this setting are limited. The multicenter phase 1-2 F-SHARP trial in the USA evaluated dose-escalated focal salvage high-dose-rate brachytherapy (DE-fsHDR) for IPR after any form of RT for localized prostate cancer, and investigated use of GC using a clinical-grade transcriptome assay. A total of 62 patients received up to 30 Gy in one (n=24) or two (n=38) fractions. The primary objective was to determine the acute RT-related grade ≥3 GU and GI toxicity rates. The median duration of follow-up was 39.4 months. No acute grade 3 toxicities occurred; two patients (3.2%) had late grade 3 toxicity. Quality of life changes did not meet criteria for a minimal clinically important difference. Three-year survival rates were 62.7% (biochemical PFS), 67.5% (radiographic PFS), 70.3% (local recurrence-free survival), amd 85.9% (metastasis-free survival); there were no significant differences between fractionation groups. Among 31 patients with GC results, higher scores were associated with worse survival outcomes. All 4 patients with GC score > 0.85 experienced biochemical, local, and metastatic recurrence. The authors conclude that DE-fsHDR is a safe and effective salvage treatment for IPR, and that GC score is a promising prognostic tool in patients undergoing salvage local therapy for IPR.