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ABSTRACT: Purpose
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.Patients and methods
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.Results
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 (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7-CD45RA-) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS.Conclusions
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.
SUBMITTER: Zhang H
PROVIDER: S-EPMC8639778 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Zhang Henan H Orme Jacob J JJ Abraha Feven F Stish B J BJ Lowe Val J VJ Lucien Fabrice F Tryggestad Erik J EJ Bold Michael S MS Pagliaro Lance C LC Choo C Richard CR Brinkmann Debra H DH Iott Matthew J MJ Davis Brian J BJ Quevedo J Fernando JF Harmsen William S WS Costello Brian A BA Johnson Geoffrey B GB Nathan Mark A MA Olivier Kenneth R KR Pisansky Thomas M TM Kwon Eugene D ED Dong Haidong H Park Sean S SS
Clinical cancer research : an official journal of the American Association for Cancer Research 20210930 23
<h4>Purpose</h4>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.<h4>Patients and methods</h4>Eighty-nine patients with oligometastatic CRPC were identified by <sup>11</sup>C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survi ...[more]