For 50 years, androgen deprivation therapies (ADTs) have been used to treat prostate cancer, but they may actually keep new immunotherapies from working and promote a recurrence of cancer if the therapies aren't timed properly.

Researchers at UT Southwestern Medical Center found that many androgen-depriving treatments suppress the patients' immune response and prevent immunotherapies from working if both are used and not properly timed.

Androgens are male hormones, and they spur the growth of prostate cancer cells.
Androgen deprivation therapies are anti-hormone treatments that reduce the levels of androgens in the body.

ADT is often used as an initial treatment for prostate cancer along with radiation therapy, especially in men who are at a higher risk of recurrence due to a high PSA level, or the cancer has spread to outside of the prostate.

"Medical ADTs have been used for a half century to treat prostate cancer, and promising clinical results for cancer immunotherapy have led to attempts to combine it and other standard-of-care therapies with immunotherapy to treat the disease," said senior author and principal investigator Dr. Yang-Xin Fu, Professor of Pathology and Immunology.
Recurrence of tumors, however, has been a problem.

"While surgical ADT — castration — works well with immunotherapy, we determined that some androgen receptor antagonists could reduce the T-cell response against prostate cancer, leading to early tumor relapse," said Dr. Fu.

"Our study shows that in some patients, this poor response could also be due to the radiation or chemotherapy itself suppressing the immune response," Fu explained.

"These treatments may reduce the tumor burden in the short term, but at the same time, they can suppress the immune response," he said, "and because they don't kill every cancer cell, resistant clones will be selected, especially when the body's immune response is not mobilized, and the tumor will relapse much more aggressively."

The study found that regulating the timing, types, and dosage of anti-androgens used with immunotherapy are key to maximizing the anti-tumor effects of combination therapy.

"We hope that our findings will cause physicians to think twice before starting chemotherapy or radiation on their cancer patients, to consider the best way to combine them with immunotherapies," he said.

"The idea is to kill the tumor cells while also considering whether these therapies are suppressing or activating the immune system."

More than 180,000 new cases of prostate cancer will be diagnosed in American men in 2016, according to the American Cancer Society, and about 1 in 7 men will be diagnosed with the disease in their lifetimes. Prostate cancer is the second leading cause of cancer deaths in men; only lung cancer is deadlier.

The study was published in Science Translational Medicine.