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.