Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in ¹¹C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

Abstract

Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. Eighty-nine patients with oligometastatic CRPC were identified by ¹¹C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (T_TR; CD8⁺CD11a^high) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (T_EM; CCR7^-CD45RA^-) were associated with improved PSA PFS. An increase in T_TR at day 14 from baseline was associated with superior OS. This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.