3347 - The Safety and Efficacy of PSMA-PET-Guided Comprehensive Radiotherapy for Oligo-Residual Disease after Treatment in High-Volume Metastatic Prostate Cancer
Presenter(s)
Q. H. Peng1, X. Qi1, W. Yu2, Y. Song3, J. H. Zhang4, X. H. Liao4, and H. Z. Li1; 1Department of Radiation Oncology, Peking University First Hospital, Beijing, China, 2Department of Urology, Peking Universtiy First Hospital, Beijing, China, 3Department of urology, Peking University First Hospital, Beijing, China, 4Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
Purpose/Objective(s): For patients with high-volume prostate cancer, progression to treatment-refractory castration-resistant prostate cancer (CRPC) remains common even after triple therapy. This study evaluates whether definitive radiotherapy directed at both the prostate and all residual metastases can delay castration resistance in patients with high-volume mHSPC (as defined by CHAARTED criteria) who achieve oligopersistent disease (=5 PSMA PET-positive lesions) following systemic therapy.
Materials/Methods: This prospective cohort study enrolled patients from a single center between 2022 and 2025. After systemic therapy, patients received definitive RT to residual active lesions: 67.5–70 Gy/25 fractions (fx) or 36.25–40 Gy/5 fx to the primary, and 60–70 Gy/25 fx or 30–40 Gy/5 fx to metastases (location-adapted simultaneous integrated boost or hypofractionation). Primary endpoints: 1)2-year non-progression to CRPC rate; 2) CBR rate (PSA<0.2ng/mL at 6mo post-RT, excluding unevaluable). Secondary endpoints included overall survival, toxicity (CTCAE v5.0), and quality of life (EORTC QLQ-C30).
Results: To date, 89 high-volume mHSPC patients were enrolled. Median age at diagnosis was 65 years (IQR: 59-68). Twenty-eight patients (96.6%) presented with clinical stage T3-T4 prostate cancer. Gleason scores were 7 in 4 patients (4.5%), 8 in 31 (34.8%), 9 in 45 (50.6%), and 10 in 6 (6.7%), three patient had missing data. Baseline PSA levels were <50 ng/mL in 21 patients (23.6%), 50-100 ng/mL in 18 (20.2%), and >100 ng/mL in 50 (56.2%). Metastatic sites included bone in 87 (97.8%), lymph nodes in 80 (89.9%), and visceral organs in 13 (14.6%). All patients received ADT plus novel hormonal therapy, with 46.0% also receiving docetaxel. After a median systemic therapy duration of 9 months (IQR: 7-13), oligopersistent status was achieved with a median of 2 residual lesions. Median pre-RT PSA was 0.045 ng/mL (range: 0-14.2). Genomic testing was performed in 41 patients (46.0%). Among the several major mutations, the mutation rates were 2.4% for BRCA1, 24.4% for BRCA2, and 26.3% for TP53. All patients underwent PSMA PET-CT prior to radiotherapy to evaluate the activity of residual lesions. As of February 2026, the median follow-up from diagnosis to last follow-up or death was 27months (IQR: 20-38 months). 3 deaths occurred. Acute genitourinary (GU) toxicities: G1(24.7%), G2(7.8%). Acute gastrointestinal (GI) toxicities: G1(24.7%), G2 (3.3%). Late genitourinary (GU) toxicities: G1(10.3%), G2(3.0%).Late gastrointestinal (GI) toxicities: G1(4.4%), G2(1.5%).CBR was 76.5% (52/68; 22 patients unevaluable at cutoff due to insufficient follow-up). A total of 10 patients progressed to CRPC. The estimated 2-year non-progression to CRPC rate after radiotherapy was 85.5% (95% CI: 77.4–94.4).
Conclusion: Comprehensive radiotherapy to all residual lesions in patients with oligopersistent high-volume mHSPC delays progression to castration-resistant stage and demonstrates a favorable safety profile.