What they showed, said Dr. Phillips, was that patients with no additional untreated lesions detected by the PSMA PET scan at baseline (a state referred to as total consolidation) were significantly less likely to develop new metastatic lesions at six months (16% vs. 63%, p=0.006) than those whose PSMA PET scan showed at least one additional lesion at baseline (a state referred to as subtotal consolidation). Patients with total consolidation of lesions also had significantly better (4.8 times greater) progression-free survival than patients whose PSMA PET scans showed additional lesions.
What this suggests, said Dr. Tran, is that the high-dose radiation treatments are not just destroying the tumors targeted by SABR, but they are changing the course of metastatic disease.
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“Importantly, patients with subtotal consolidation had more new lesions,” he said. “It isn’t just that the untreated lesions are continuing to grow. This phenomenon suggests that treating macroscopic metastatic disease alters the natural history of the disease; that existing macroscopic metastases can influence the non-visible or microscopic disease development into new visible metastases.”
Currently, PSMA PET scans are not widely available for physicians to use in treatment planning, said Dr. Phillips, but this study should add to the growing body of evidence of their usefulness. “That extra imaging information gave us extra power to prevent disease progression and new metastases,” he said. “In our experience, these scans add to our ability to control the disease.”
Finally, the trial also analyzed circulating tumor DNA (ctDNA) using an ultra-sensitive liquid biopsy test developed by Max Diehn, MD, PhD, an associate professor of radiation oncology at Stanford University. Using ctDNA, the group identified a specific mutational signature that predicted which men most benefited from SABR.
“There is now accumulating evidence that SABR is effective for patients with oligometastatic disease, but there are currently no biomarkers that help us to determine who benefits most from this treatment. Our findings represent the first molecular marker that may predict a benefit of SABR in patients with oligometastatic disease. If additional validation of this mutational signature bears out in other cohorts, then we could potentially use it to personalize which patients with oligometastatic prostate cancer should receive SABR,” commented Dr. Diehn.
The abstract, “Primary outcomes of a phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer (ORIOLE),” will be presented in detail at ASTRO’s 61st Annual Meeting in Chicago. To schedule an interview with Dr. Phillips and/or outside experts, contact ASTRO’s media relations team.
