A highly focused, intense doses of radiation called stereotactic ablative radiation (SABR), also known as stereotactic body radiation therapy (SBRT), gives an intense dose of radiation concentrated on a tumor while limiting the dose to the surrounding organs.
SABR/SBRT differs from conventional radiation therapy. This approach typically used to treat smaller tumors that have been detected early, delivers a high radiation dose to the target that can potentially eliminate cancer.
In a subset of men with hormone-sensitive prostate cancers, SABR/SBRT may slow the progression of the disease that has spread to a few separate sites in the body. This is the conclusion based on results from the randomized phase II ORIOLE trial which was supported by the Prostate Cancer Foundation, Movember Foundation, Commonwealth Foundation, Nesbitt-McMaster Foundation, Ronald Rose & Joan Lazar and the National Institute of Health.
A report on the study is published on March 26, 2020, in the journal JAMA Oncology.
The ORIOLE trial (Stereotactic Body Radiation for Prostate Oligometastases; NCT02680587), led by researchers at the Johns Hopkins Kimmel Cancer Center, compared the effectiveness of SABR/SBRT versus “wait and watch” observation in recurrent cases of oligometastatic prostate cancer.
“It has been a longstanding question, especially important now in the era of immunotherapy, whether any type of radiation, and SABR/SBRT specifically, can stimulate the immune system,” said Phuoc Tran, M.D., Ph.D., professor of radiation oncology and molecular radiation sciences at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center.
Tran, who is the study leader, co-directs the Kimmel Cancer Center’s Cancer Invasion and Metastasis program with Andrew Ewald, Ph.D., and Ashani Weeraratna, Ph.D.. The program studies the process by which cancers spread, an is designed to expand and develop better treatments for patients with advanced cancers.
“Our trial offers the best data to date to suggest that SABR can cause a systemic immune response,” Tran added.
Oligometastatic cancers are those that have spread from a primary tumor to one to three sites within the body. Of the estimated 1.3 million men worldwide newly diagnosed with prostate cancer each year, some 20% have metastatic disease, although it’s unclear what percentage of those overall have oligometastatic cancers.
Prostate cancer is the third most common cancer and the most common cancer among men in the United States, resulting in about 30,000 deaths annually.
Metastatic prostate cancer is incurable, and men with recurrent hormone-sensitive cancers may prefer to delay one of the standard treatments, an antihormone therapy called androgen deprivation therapy.
It often causes unpleasant side effects, including erectile disfunction, loss of bone density leading to fractures, loss of muscle mass and physical strength, fatigue, weight gain and growth of breast tissue among other things.
Of a total of 80 patients screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were enrolled in the trial and randomized in a 2:1 ratio to receive SABR or observation.
Among these 54 men, the disease progressed within six months in seven out of 36 (19%) of participants treated with SABR/SBRT, compared to 11 out of 18 participants (61%) undergoing observation alone. The risk of new cancers at six months was also lower, occurring in 16% of those receiving SABR compared to 63% of those under observation.
There were no significant differences in clinically meaningful side effects or in reports of pain related to the treatment between the two groups, the study found. The average age of the men on the ORIOLE trial was 68-years old, and most participants were white.
Analysis of immune system white cells in blood drawn from the patients indicated that SABR/SBRT-treatment was associated with an expanded population of T-cells, suggesting that the treatment stimulated a full-body immune system response to their cancers, according to Tran.
The findings of the study, which took pace from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis, suggests that SABR/SBRT might be usefully paired with other immunotherapies to treat recurrent oligometastatic prostate cancers. However, Tran cautioned that any potential benefits of such combined therapy will need to be tested in future clinical trials.
The research team also detected a set of tumor mutations in genes known to be important for suppressing cancer development in some patients that correlated with a higher risk of cancer progression even among those undergoing SABR/SBRT. “This may be a molecular signature which is indicative of the underlying biology of the patient’s cancer,” said Tran.
The biomarker could help clinicians know “…which patients are going to benefit the most from a metastasis-directed therapy like SABR/SBRT compared to a systemic treatment such as chemotherapy,” Tran explained.
“The results from the ORIOLE study also suggest that SABR/SBRT treatment may remove or affect signals that promote the development of micrometastases in recurrent oligometastatic prostate cancer, rather than just “resetting” the clock on the disease until metastases grow large again,” Tran noted.
Tran and his team will continue with phase II studies to determine if they can increase the number of participants with slower disease progression. In the ORIOLE trial, patients with metastatic lesions in the bone were most likely to have their cancers recur in a new bone site.
To target these new metastatic bone lesions, Tran and colleagues have another clinical trial called RAVENS that combines SABR/SBRT with a drug called radium-223 (Xofigo®; Bayer) that targets metastatic cancer in the bones.
 Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. Published online March 26, 2020. doi:10.1001/jamaoncol.2020.0147