Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces anti-tumor immunity in clinical and preclinical studies, but immunological biomarkers are lacking.
89 patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016-December 2019 and treated with SABR. Pre-specified co-primary 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 one year and 21% at two years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no Grade {greater than or equal to} 3 AEs were observed. Baseline high levels of tumor reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7-CD45RA-) was associated with improved PSA PFS. An increase in TTR 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 oligometastatic CRPC patients treated with SABR.
ClinicalTrials.gov Identifier: NCT02816983 Oligometastatic Prostate cancer Radiotherapy Augmenting T Immune Cells (OPeRATIC).
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Sep 30 [Epub ahead of print]
Henan Zhang, Jacob J Orme, Feven Abraha, B J Stish, Val J Lowe, Fabrice Lucien, Erik J Tryggestad, Michael S Bold, Lance C Pagliaro, C Richard Choo, Debra H Brinkmann, Matthew J Iott, Brian J Davis, J Fernando Quevedo, William S Harmsen, Brian A Costello, Geoffrey B Johnson, Mark A Nathan, Kenneth R Olivier, Thomas M Pisansky, Eugene D Kwon, Haidong Dong, Sean S Park
Department of Immunology, Mayo Clinic., Division of Medical Oncology, Mayo Clinic., Department of Biostatistics, Mayo Clinic., Department of Radiation Oncology, Mayo Clinic., Radiology, Mayo Clinic., Urology, Mayo Clinic., Department of Radiology, Mayo Clinic., Oncology, Mayo Clinic., Radiation Oncology, Mayo Clinic., Medical Oncology, Mayo Clinic., Health Sciences Research, Mayo Clinic., Dept of Radiology and Dept of Immunology, Mayo Clinic., Department of Urology, Mayo Clinic., Immunology and Urology, Mayo Clinic., Radiation Oncology, Mayo Clinic .