SABR Promising Alternative to ADT for Oligometastatic Prostate Cancer

Study findings posit stereotactic ablative radiotherapy (SABR) as a promising treatment for patients with recurrent hormone-sensitive oligometastatic prostate cancer who want to delay starting androgen deprivation therapy (ADT; JAMA Oncol. 2020 Mar 26. Epub ahead of print).

“Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of [ADT],” explained lead investigator Ryan Phillips, MD, PhD, Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues, who conducted the Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 clinical trial.

Between May 2016 and March 2018, a total of 54 patients (median age, 68 years) with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases evident via conventional imaging who had not received ADT within 6 months of enrollment or for ≥3 years total were enrolled in the study from 3 radiation treatment facilities in the United States.

These patients were randomized in a 2:1 ratio to receive SABR (n = 36) or observation (n = 18). The primary end point of the study was progression at 6 months by increase in prostate-specific antigen level, progression detected via conventional imaging, symptomatic progression, ADT initiation for any reason, or death.

The secondary end points were SABR-based toxicities, 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 detecting metastatic disease.

Overall, 7 (19%) recipients of SABR and 11 (61%) patients undergoing observation had progression at 6 months (P = .005). Furthermore, SABR was found to improve the median progression-free survival (not reached vs 5.8 months, respectively; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002).

The risk for new lesions at 6 months was reduced from total consolidation of PSMA radiotracer-avid disease (16% in recipients of SABR vs 63% in patients who underwent observation; P = .006).

There were no toxicities grade ≥3 reported. In addition, T-cell receptor sequencing led to the detection of significant increased clonotypic expansion after SABR and a correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).

“Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR,” said Dr Phillips and colleagues.

“These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates,” they concluded.—Hina Porcelli