Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial


Ryan Phillips 1, William Yue Shi 2, Matthew Deek 1, Noura Radwan 1, Su Jin Lim 3, Emmanuel S Antonarakis 3, Steven P Rowe 4 5, Ashley E Ross 5, Michael A Gorin 4 5, Curtiland Deville 1, Stephen C Greco 1, Hailun Wang 1, Samuel R Denmeade 3, Channing J Paller 3, Shirl Dipasquale 1, Theodore L DeWeese 1 3 5, Daniel Y Song 1 3 5, Hao Wang 3, Michael A Carducci 3, Kenneth J Pienta 3 5, Martin G Pomper 4 5, Adam P Dicker 6, Mario A Eisenberger 3, Ash A Alizadeh 7, Maximilian Diehn 2, Phuoc T Tran

Main idea: Treatment with stereotactic ablative radiotherapy for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by prostate-specific membrane antigen -targeted positron emission tomography. Stereotactic ablative radiotherapy induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from stereotactic ablative radiotherapy.


Importance: Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).

Objective: To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.

Design, setting, and participants: The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.

Interventions: Patients were randomized in a 2:1 ratio to receive SABR or observation.

Main outcomes and measures: The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.

Results: In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).


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