Targeted High-Dose Radiation Improves PFS, Progression in Oligometastatic Prostate Cancer | OncLive

Targeted High-Dose Radiation Improves PFS, Progression in Oligometastatic Prostate Cancer

October 16, 2019

In men with oligometastatic prostate cancer, treatment with stereotactic ablative radiation led to significant improvements in progression-free survival, especially in highrisk mutation-negative patients, and confirmed the value of tests for predicting benefit from SABR, according to findings from the phase II ORIOLE trial presented at the 61st Annual Meeting of the American Society for Radiation Oncology.

Ryan Phillips, MD, PhD

In men with oligometastatic prostate cancer (OMPC), treatment with stereotactic ablative radiation (SABR) led to significant improvements in progression-free survival (PFS), especially in highrisk mutation-negative patients, and confirmed the value of tests for predicting benefit from SABR, according to findings from the phase II ORIOLE trial presented at the 61st Annual Meeting of the American Society for Radiation Oncology. SABR also stimulated levels of immune system activity that were thought impossible to achieve in prostate cancer.1

Patients (N = 54) were randomized 2:1 to SABR or observation for 6 months following evidence of disease spread to a limited number of sites outside the prostate after treatment with surgery or radiation. Those in the treatment arm received SABR to the metastatic sites outside of the prostate.

More than a year after treatment, median PFS was not reached in the SABR arm versus 5.8 months in the observation arm (HR, 0.30; 95% CI, 0.11-0.81; P =.0023). At 6 months, 19% of patients in the SABR arm experienced progression compared with 61% in the observation arm (P = .005). Neither arm received any additional treatment.

“ORIOLE provides additional randomized trial data to support what previous studies have been suggesting,” lead author Ryan Phillips, MD, PhD, chief resident in radiation oncology at the Johns Hopkins School of Medicine in Baltimore, Maryland, said in a news release.2 “Compared with retrospective reports, our study provides a higher level of evidence that SABR benefits these patients because we can see how the patients who didn’t get SABR did in comparison.”

Previous results have demonstrated that high-dose radiation is safe and effective for men with localized or nonmetastatic prostate cancer. However, physicians have generally considered OMPC, cancer that has been treated and later returned to a limited number of other parts of the body (≤3 sites), to be incurable.

The primary endpoint in ORIOLE, the second randomized clinical trial to report findings on SABR for OMPC, was progression at 6 months as assessed by prostate-specific antigen increase, conventional imaging, or symptomatic decline. Thirty-five patients in the SABR arm received prostate-specific membrane antigen-based positron emission tomography (PET)/ computed tomography (CT) imaging at baseline and at 6 months. The 19 patients who had total consolidation, meaning no additional untreated lesions, had significantly longer median PFS (unreached vs 11.8 months; P =.003) and distant metastasis-free survival (29 vs 6.0 months; P = .0008) compared with those who had subtotal consolidation (n = 16). Furthermore, patients with total consolidation were less likely to develop new lesions at 6 months (16% vs 63%; P = .006).

“Importantly, patients with subtotal consolidation had more new lesions. It isn’t just that the untreated lesions are continuing to grow,” Phuoc Tran, MD, PhD, principal investigator of the trial and an associate professor of radiation oncology and molecular radiation sciences at the Johns Hopkins Kimmel Cancer Center, said in a news release. “This phenomenon suggests that treating macroscopic metastatic disease alters the natural history of the disease; that existing macroscopic metastases can influence the nonvisible or microscopic disease development into new visible metastases.”

Tran added that SABR also induced an expansion of more T-cell clones. Investigators found “significant, measurable changes” in the T cells of patients on the SABR arm when they analyzed blood cells collected prior to radiation therapy and 90 days after treatment.

“This is the first bit of evidence that I’m aware of showing that SABR can induce a systemic immune response in patients with prostate cancer,” Tran said. “Cancer of the prostate is a tumor that does not typically incite a response from the immune system, so seeing this response is exciting. There is still much work to be done to understand how radiation and the immune system interact.”

ORIOLE investigators used bone scans, magnetic resonance imaging, and CT—all standard tests—to identify eligible patients based on metastatic sites. But prostate-specific membrane antigen PET, a more sensitive, advanced imaging technology, was used to positive effect. And circulating tumor DNA testing was also found helpful in this context. “There may be a measurable circulating mutational profile that would help us determine who will benefit versus who would do better with another approach,” Phillips said.

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