Stereotactic body radiation reduced the likelihood for future PSA rises and significantly prolonged survival in men with oligometastatic prostate cancer (≤3 metastases), according to recently published findings from ORIOLE, a phase II, multicenter, randomized, observation-controlled trial.
Stereotactic body radiation (SABR) reduced the likelihood for future PSA rises and significantly prolonged survival in men with oligometastatic prostate cancer (≤3 metastases), according to recently published findings from ORIOLE, a phase II, multicenter, randomized, observation-controlled trial.
Additional data from the study, published in JAMA Oncology (March 26, 2020 [Epub ahead of print]), showed that SABR had a very favorable toxicity profile-it was not associated with any grade 3 or higher adverse events nor adverse effect on quality of life-and suggested that SABR may act by inducing a systemic adaptive immune response. A potential biomarker for predicting response to SABR was also identified, said Phuoc T. Tran, MD, PhD, of Johns Hopkins School of Medicine, Baltimore.
“Single-institution studies and limited prospective data have recently suggested that SABR may be effective for men whose prostate cancer had spread. Now, we have data from a randomized controlled trial confirming those observations,” Dr. Tran told Urology Times.
“The accumulating evidence are convincing supporting clinical practice change, but ultimately the data need to be validated in larger, phase III clinical trials.”
ORIOLE enrolled men at three Johns Hopkins area hospitals. Eligible patients had hormone-sensitive prostate cancer recurring after definitive surgical or radiation treatment, one to three asymptomatic metastases identified by conventional imaging, and had not received androgen deprivation therapy (ADT) during the previous 6 months or for ≥3 years total. They were randomized 2:1 to receive SABR or observation.
Progression at 6 months, a composite endpoint including rise in PSA, progression on conventional imaging, symptomatic progression, ADT initiation, or death, was the primary outcome measure for the study. It occurred at a significantly lower rate in the SABR group compared with the control arm (19% vs. 61%; p=.005). Median progression-free survival, analyzed as a predefined secondary endpoint, was not yet reached in the SABR arm and occurred at 5.8 months in the observation arm (p=.002).
Patients also underwent imaging with prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET). Data from that more sensitive technique for metastasis detection showed that men who achieved total consolidation of detectable metastases (ie, absence of untreated lesions detected by PSMA PET scan at baseline) were at significantly lower risk for developing new metastatic lesions at 6 months compared with those who had subtotal consolidation (ie, one or more additional lesions) (16% vs. 63%; p=.006). In addition, progression-free survival was almost five-fold greater among patients achieving total consolidation of lesions than among patients whose PSMA PET scans showed additional lesions.
“These findings suggest that total consolidation of detectable metastases may eliminate or dampen signals that promote development of micrometastases,” said Dr. Tran.
Analyses of peripheral blood mononuclear cells collected at baseline and 90 days after treatment showed statistically significant, measurable changes in the T cells of patients in the SABR arm, but no change in the T cells of men in the observation arm.
“The magnitude of change in the immune system response was similar to what would be seen after a vaccination, suggesting that the radiation therapy may spark the immune system to more aggressively fight the cancer,” Dr. Tran said.
“This is the first piece of evidence that I am aware of showing that SABR can induce a systemic immune response in patients with prostate cancer.”
Liquid biopsy using plasma samples to analyze circulating tumor DNA identified a specific mutational signature that predicted which men most benefited from SABR.
“While evidence is accumulating that SABR is effective treatment for patients with oligometastatic disease, there are currently no biomarkers to help us determine which patients are most likely to benefit. Our study is the first to identify a potentially predictive molecular marker,” Dr. Tran said.
As next steps, researchers will be testing rationale combinations of SABR with systemic therapies using precision medicine informed approaches.
Dr. Tran receives consulting fees and honoraria from RefleXion Medical, Inc., research funding from RefleXion Medical, Inc, Astellas Pharma, and Bayer Healthcare. He is co-owner of Patent#: 9114158 licensed to Natsar Pharm. Dr. Tran is funded by the Nesbitt-McMaster Foundation, Ronald Rose and Joan Lazar, Movember-PCF and the NIH (R01CA166348, U01CA2120007 & R21CA223403).