Intense and targeted radiotherapy could slow progression of certain prostate cancers

By Sally Robertson, B.Sc.Mar 26 2020

A new study has identified that highly targeted and strong doses of a type of radiotherapy called stereotactic ablative radiation (SABR) could slow disease progression among a subgroup of men who have hormone-sensitive prostate cancer that has only spread to a few other parts of the body.

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The findings are based on the primary outcomes of a phase II randomized clinical trial called ORIOLE. The study, which began in 2016 and was led by researchers at Johns Hopkins Kimmel Cancer Center, compared the effectiveness of the “wait and watch” approach with SABR treatment among men with recurring oligometastatic prostate cancer.

"It has been a longstanding question, especially important now in the era of immunotherapy, whether any type of radiation, and SABR specifically, can stimulate the immune system," says study leader Phuoc Tran.

Tran, who is a professor of molecular radiation sciences at the Johns Hopkins University School of Medicine is co-director of the center’s “Cancer Invasion and Metastasis” program, along with post-docs Andrew Ewald and Ashani Weeraratna. The goal of the program is to study and understand the process of cancer metastasis in order to improve on or develop therapies for the treatment of advanced cancers.

Now, Tran says: "Our trial offers the best data to date to suggest that SABR can cause a systemic immune response.”

About oligometastatic cancers

An oligometastatic cancer is one that has spread from the primary site of disease to one to three other parts of the body

Prostate cancer is the third most prevalent cancer worldwide and the most common cancer among men in the US, where it kills approximately 30,000 every year.

An estimated 1.3 million men globally are diagnosed with prostate cancer every year. Of those newly diagnosed cases, about twenty percent have a disease that has spread (metastasis), although it is not known exactly how many of them have oligometastatic cancer.

Metastatic prostate cancer cannot be cured and men who suffer from recurrent hormone-sensitive cancers may opt to delay receiving the standard treatment (androgen deprivation therapy) because it commonly causes a number of adverse side effects, including erectile dysfunction, reduced bone density, fractures, muscle loss, tiredness, loss of strength and gynecomastia (breast tissue growth).

What did the researchers find?

As reported in the journal JAMA Oncology, the ORIOLE trial found that among 54 patients (aged an average of 68 years) with recurrent oligometastatic prostate cancer, disease progression was observed within six months for seven of 36 (19%) participants who received SABR, compared with 11 of 18 (61%) participants who underwent the “wait and watch” observation approach.

Tran and team also found that at six months since enrollment, the risk for new cancers having developed was significantly lower among the SABR group than among the observation group, at 16% versus 63%.

Participants did not report any significant between-group differences in side effects or pain felt in relation to the two treatment regimens.

What are the implications of the study?

On analyzing immune cells in blood samples taken from the patients, the researchers found that the SABR approach was associated with the expansion of T cell populations. Tran says this suggests that the radiotherapy had induced a systemic immune response to the cancers.

The study also suggests that it could be clinically beneficial to couple SABR with other immunotherapies as a treatment approach to the recurrent cancers, but Tran also warns that such potential benefits would first need testing in clinical trials.

The researchers also identified a set of tumor gene mutations that are known to be involved in the suppression of cancer and the presence of this mutational signature was associated with an increased risk for disease progression, including among the men who received SABR.

"This may be a molecular signature which is indicative of the underlying biology of the patient's cancer."

Professor Tran Phuoc, Johns Hopkins University School of Medicine

He adds that this potential biomarker could help indicate to clinicians "which patients are going to benefit the most from a metastasis directed therapy like SABR" compared to a systemic treatment such as chemotherapy.”

Furthermore, Tran says the findings also suggest that treatment with SABR may reduce or even eliminate the cell signaling that promotes micrometastases in cases of recurrent oligometastatic prostate cancer, as opposed to simply halting disease until metastatic tumors become large again.  

Next, the researchers intend to conduct further phase II studies to see whether they can slow disease progression in more patients.

The team is also conducting another trial called RAVENS that targets newly formed metastatic bone lesions with a combination of SABR and the drug radium-23.