Phase II Evaluation Of Stereotactic Ablative Radiotherapy (SABR) in 11C-Choline PET/CT (Cho-PET)-Identified Oligometastatic Castration-Resistant Prostate Cancer (CRPC)

Abstract

Outcomes for metastatic castration-resistant prostate cancer (CRPC) remain poor. We prospectively sought to improve clinical outcomes in a subgroup of CRPC patients (pts) with oligometastases identified by 11C-Choline (Cho)-PET and treated with stereotactic ablative radiotherapy (SABR). This is a single arm, single institution Phase II study which enrolled 94 pts from Aug 2016-Dec 2019; 4 pts voluntarily withdrew and 1 pt had only 1 month follow up. Nine pts who received 8 Gy in 1 were also included in survival analysis. Eligibility included ECOG 0-2, pathologically proven prostate cancer, ≤ 3 metastases identified on Cho-PET, testosterone < 50 ng/dL on androgen deprivation therapy, and life expectancy > 6 months. Primary endpoints were 2-year overall survival (OS) and 1-year PSA-progression (Prostate Cancer Working Group criteria). Secondary endpoints included 1-year SABR-treated metastasis failure (MF) and 6-month rates of grade ≥ 3 adverse events (AEs) per CTCAE V4.0. Peripheral blood samples were collected for exploratory immunologic biomarker analyses. 89 pts are included in this analysis, and median age was 71 years. 58 pts had one lesion, 23 pts two lesions, and 8 pts three lesions. Prior to SABR (n = 80), 61%, 52%, and 20% had progressed on second-line chemotherapy, abiraterone, or enzalutamide, respectively; 38% progressed on both chemotherapy and next generation androgen axis inhibitors. Median PSA at SABR was 0.7 (IQR 0.25, 3.1), and 64% had PSA < 2 ng/mL. Mode dose and fractionation was 20 Gy and 1. At median follow-up of 23 months, median OS was 29 mos. 1- and 2-year OS was 96% (95% CI: 91-100) and 80% (70-92), respectively, for all and also for SABR pts. The cumulative incidence of PSA progression was 58% (48-71) and 76% (67-88), and MF was 12% (6-24) and 18% (11-32) at 1-and 2-years, respectively, for SABR pts. No grade ≥ 3 AEs were noted. Grade 2 AEs included fatigue (1%), fracture (3%), and flare-up pain (8%) in SABR pts. We observed an estimated 2-year OS of 80% in heavily-treated CRPC pts after metastasis-directed therapy to Cho-PET-defined oligometastatic sites with no grade ≥ 3 AEs. Approximately 20% of pts did not have a change or additional systemic therapy following SABR. These results are favorable compared to historical series and support the study of Cho-PET and SABR in CRPC pts in Phase III trials.