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

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, 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

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.

Trial registration: ClinicalTrials.gov NCT02816983.

Conflict of interest statement

Conflicts of Interest

The authors report no other relevant conflicts of interest.

©2021 American Association for Cancer Research.

Figures

Fig 1.. Patient outcomes.
Fig 1.. Patient outcomes.
(A) Overall survival of all patients in the study. (B) PSA progression-free survival of all patients in the study. (C-D) Local and distant progression-free survival by modality (conventional versus stereotactic RT).
Fig 2.. High baseline T TR levels…
Fig 2.. High baseline TTR levels predict superior PSA, local, and distant PFS.
(A) Biochemical progression-free survival. (B) Local progression-free survival. (C) Distant progression-free survival.
Fig 3.. T TR cell changes after…
Fig 3.. TTR cell changes after radiotherapy predict OS in oligometastatic CRPC.
(A) TTR cells are defined by expression of both CD8 and CD11a. (B) Patients with increasing TTR levels at day 14 after radiotherapy to oligometastases experience superior OS in CRPC.

Source: PubMed

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