According to findings from the phase I/II F-SHARP trial reported by Solanki et al in the Journal of Clinical Oncology, dose-escalated focal salvage high–dose rate brachytherapy demonstrated favorable disease control with low rates of severe toxicity in patients with locally recurrent prostate cancer following definitive radiotherapy. The investigators also found that genomic classifier scores may help identify patients at increased risk of disease progression who could benefit from treatment intensification.
Study Details
F-SHARP was a multicenter, nonrandomized phase I/II trial involving 62 patients with biopsy-confirmed intraprostatic recurrence following definitive radiotherapy for localized prostate cancer. Eligible patients had no evidence of regional or distant metastasis on imaging. Between August 2017 and December 2023, 24 patients (38.7%) received a single fraction of focal salvage high–dose rate brachytherapy, and 38 (61.3%) received two fractions, with treatment delivering up to 30 Gy. Concurrent androgen-deprivation therapy was permitted and administered to five patients (8.1%).
The primary endpoint was acute grade 3 or higher genitourinary or gastrointestinal toxicity within 3 months of treatment. Secondary endpoints included disease control, survival, late toxicity, and patient-reported quality of life. Investigators also performed an exploratory genomic analysis using the Decipher Prostate genomic classifier on recurrent tumor biopsy specimens from 31 patients to assess associations between genomic risk and clinical outcomes.
Key Results
After a median follow-up of 39.4 months (interquartile range = 23.9–60.9 months), no patients experienced acute grade 3 or higher genitourinary or gastrointestinal toxicity. Two patients (3.2%), both in the two-fraction group, developed late grade 3 urethral strictures. Patient-reported quality-of-life changes did not reach thresholds for minimal clinically important differences, and no significant differences in toxicity or quality of life were observed between fractionation groups.
At 3 years, biochemical progression–free survival was 62.7% (95% confidence interval [CI] = 46.6%–75.1%), radiographic progression–free survival was 67.5% (95% CI = 51.9%–79.1%), local recurrence–free survival was 73.0% (95% CI = 57.5%–83.6%), and metastasis-free survival was 85.9% (95% CI = 72.2%–93.1%). The 3-year rate of freedom from palliative androgen-deprivation therapy was 83.1%. No significant differences in disease control were observed between the single- and two-fraction groups (all P > .05).
Among the 31 patients with genomic classifier results, higher scores were significantly associated with worse biochemical progression–free survival (hazard ratio [HR] = 1.55, P = .03), radiographic progression–free survival (HR = 2.92, P = .004), local recurrence–free survival (HR = 2.50, P = .02), and metastasis-free survival (HR = 3.62, P = .02). Patients with very high genomic classifier scores (> 0.85) experienced biochemical, local, and metastatic recurrence during follow-up, whereas patients with low or intermediate scores experienced no local or metastatic progression.
The investigators concluded: “[Dose-escalated focal salvage high–dose rate brachytherapy] is a safe and effective salvage treatment for [intraprostatic radiorecurrence]. [Genomic classifier] score is a promising prognostic tool in patients undergoing salvage local therapy for [intraprostatic radiorecurrence] and warrants further study to guide treatment intensification.”
Abhishek A. Solanki, MD, MS, of the Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois, and Loyola University Medical Center, Maywood, Illinois, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Cardinal Bernardin Cancer Center Translational Research Development Grant. For full disclosures of the study authors, visit ascopubs.org.
