Stereotactic body radiation therapy (SBRT) — a form of targeted, high-dose radiation therapy — significantly extends the time without detectable disease progression when given to prostate cancer patients with limited metastatic lesions, data from a Phase 2 trial show.
These findings were presented at the recent 2019 American Society for Radiation Oncology (ASTRO) Annual Meeting in Chicago, in the presentation “Primary outcomes of a phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer (ORIOLE)” (LBA 3).
Radiation has previously been demonstrated to be an effective treatment for prostate cancer that has not spread. However, whether this treatment is effective for oligometastatic prostate cancer — cancer that has spread to a limited number of places in the body — remains unclear.
The ORIOLE Phase 2 trial (NCT02680587) was designed to address this in prostate cancer patients whose cancer had returned after surgery or radiation treatment, and who had one to three metastatic lesions outside the prostate.
It included 54 men with recurrent hormone-sensitive prostate cancer, who were were randomized to one of two groups: one received no additional treatment and was observed for six months; the other was treated with SBRT targeted at the metastatic lesions.
SBRT essentially involves the targeted delivery of very high amounts of radiation to tumor sites over the course of just one or a few treatment sessions.
Results from ORIOLE showed that patients given SBRT went longer without disease progression, and were much less likely to see a rise in their PSA levels — a marker of disease progression.
After six months, 61% of patients in the observation (no further treatment) arm had evidence of disease progression (defined as an increase in cancer biomarkers in the blood, worsening symptoms, etc.). In the SBRT group, 19% progressed — a statistically significant difference.
Put another way, the median progression-free survival (PFS) time in the no-treatment group was 5.8 months, whereas median PFS after more than one year had not been reached in the SBRT group. (Since a majority of participants in this group had not progressed, no value could be calculated as the median).
“Single-institution studies and limited prospective data have recently suggested that high-dose, targeted radiation may be effective for men whose prostate cancer had spread, and now these ORIOLE randomized data confirm those observations,” Ryan Phillips, MD, PhD, a resident at Johns Hopkins and study co-investigator, said in a press release.
Trial data also suggest that SBRT elicited “significant, measurable changes” in participants’ T-cells, immune cells that are critical in fighting tumors. These immune changes were only observed in participants treated with SBRT, suggesting that the radiation may kill tumors by activating an anti-cancer immune response, in addition to directly damaging tumor cells.
“The magnitude of change in the immune system response was similar to what you see after a vaccination,” Phillips said.
Another study co-investigator, Phuoc Tran, MD, PhD, who is also a professor at Johns Hopkins, added: “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.”
The researchers also found that a mutation signature they could detect in circulating cancer DNA (that is, cancer cell DNA that can be found in the bloodstream) could predict who would or would not respond to SBRT therapy.
“There is now accumulating evidence that [SBRT] 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 [SBRT] in patients with oligometastatic disease, said Max Diehn, MD, PhD, study co-investigator and Stanford professor.
“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 [SBRT],” Diehn added.
Researchers also highlighted a novel imaging tool in the study: a prostate-specific membrane antigen (PSMA) PET scan, which is basically a PET scan that looks for prostate cancer-specific molecules, allowing more sensitive detection of small tumor growths.
Patients in the SBRT arm underwent PSMA PET scans before and after treatment. Some had small metastases that had not been detected by other imaging modalities, and these people were significantly more likely to develop new metastases than patients with no additional lesions (63% vs. 16% developed new metastases at six months).
“That extra imaging information gave us extra power to prevent disease progression and new metastases,” Phillips said. “In our experience, these scans add to our ability to control the disease.”