Dose-Escalated Focal Salvage High-Dose-Rate Brachytherapy and Genomic Classifier Risk Stratification in Radiorecurrent Prostate Cancer: The F-SHARP Phase I/II Clinical Trial

Purpose Prospective data on the management of intraprostatic radiorecurrence (IPR) after definitive radiotherapy (RT) and use of genomic classifiers (GC) in this setting are limited. We hypothesized that dose-escalated focal salvage high-dose-rate brachytherapy (DE-fsHDR) would be safe and effective, and that GC would risk stratify patients who may benefit from treatment intensification. Methods F-SHARP is a multi-institutional phase I/II trial of DE-fsHDR for IPR after any form of RT for localized prostate cancer. Patients received up to 30 Gy in 1-2 fractions. The primary objective was to determine the acute RT-related grade ≥3 CTCAE v4.03 genitourinary and GI toxicity rates. Secondary end points included all-grade toxicity, quality of life (QoL; EPIC-26 and International Prostate Symptom Score), disease control, and survival. GC analysis used a clinical-grade transcriptome assay (Veracyte, San Diego, CA). Time-to-event outcomes included biochemical progression-free survival (bPFS), radiographic progression-free survival (rPFS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS). Results Twenty-four participants received one fraction and 38 received two fractions (N = 62). The median follow-up was 39.4 months. No acute grade 3 toxicities occurred. Two patients (3.2%) had late grade 3 toxicity. QoL changes did not meet criteria for a minimal clinically important difference. Three-year survival rates were 62.7% (bPFS), 67.5% (rPFS), 73.0% (LRFS), and 85.9% (MFS); there were no differences between fractionation groups (all P > .05). Among 31 patients with GC results, higher scores were associated with worse bPFS, rPFS, LRFS, and MFS. All patients with GC score >0.85 (n = 4) experienced biochemical, local, and metastatic recurrence. Conclusion DE-fsHDR is a safe and effective salvage treatment for IPR. GC score is a promising prognostic tool in patients undergoing salvage local therapy for IPR and warrants further study to guide treatment intensification.