In a phase II trial reported in JAMA Oncology, Phillips et al found that stereotactic ablative radiotherapy (SABR) was associated with improved outcomes vs observation in men with oligometastatic prostate cancer. The benefit was augmented in patients with total consolidation of disease identified by prostate-specific membrane antigen (PSMA)-targeted positron-emission tomography (PET).
As noted by the investigators, complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen-deprivation therapy (ADT) in this setting.
The trial, conducted at three affiliated radiation treatment facilities in the United States, enrolled 54 men with recurrent hormone-sensitive prostate cancer and one to three metastases detected by conventional imaging who had not received ADT within 6 months of enrollment or for ≥ 3 years in total. Patients were randomly assigned 2:1 between May 2016 and March 2018 to receive SABR (n = 36) or observation (n = 18).
SABR was planned based on the size and location of each lesion, with doses ranging from 19.5 to 48.0 Gy in three to five fractions. The primary outcome measure was disease progression at 6 months, with progression defined as prostate-specific antigen level increase, and with disease progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death.
Disease progression at 6 months occurred in 7 (19%) of 36 patients receiving SABR and 11 (61%) of 18 undergoing observation (P = .005). With a median follow-up of 18.8 months, median progression-free survival was not reached vs 5.8 months (hazard ratio = 0.30, P = .002).
A total of 16 SABR patients had baseline PET-avid lesions that were not included in the treatment fields. Disease progression at 6 months was observed in 1 (5%) of 19 evaluable patients with no untreated lesions vs 6 (38%) of 16 with any untreated lesions (P = .03). Development of new metastatic lesions at 180 days was observed in 3 (16%) of 19 vs 10 (63%) of 16, respectively (P = .006).
Peripheral T-cell receptor sequencing in patients receiving SABR showed enhanced differential clonotype expansion and clusters of similar expanded T-cell receptors at 90 days, and clinical benefit associated with greater baseline clonality. In addition, it was found that progression-free survival was significantly improved with SABR vs observation in a subgroup of patients who were high-risk mutation–negative but not in a high-risk mutation–positive subgroup. No grade ≥ 3 adverse events were observed in the SABR group.
The investigators concluded, “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. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.”
Phuoc T. Tran, MD, PhD, of the Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Nesbitt-McMaster Foundation, Ronald Rose and Joan Lazar, the Movember Foundation and Prostate Cancer Foundation, the National Cancer Institute, and others. For full disclosures of the study authors, visit jamanetwork.com.
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