Long-term hormonal therapy benefits men with locally advanced prostate cancer

By: Charles Schmidt

Hormonal therapy, also known as androgen-deprivation therapy, can be a powerful weapon in the fight against prostate cancer because it deprives malignant cells of the fuel they need to grow. Androgens — meaning the family of male sex hormones that includes testosterone — contribute to physical characteristics such as a deeper voice, thick facial hair, and increased muscle strength and bone mass. But when prostate cancer develops, testosterone also contributes to tumor growth and progression. Depending on the specific treatment used, hormonal therapy can either stop the body from making testosterone or prevent it from interacting with cancer cells.

Though it was once reserved solely for treating prostate cancer that has spread, doctors now also combine hormonal therapy with radiation to treat locally advanced tumors that have not yet spread to more distant locations, such as the bones. Hormonal therapy reduces the chance that a tumor will progress or return, and it makes radiotherapy more effective at controlling prostate cancer. But it also causes side effects such as weight gain and bone loss, and the optimal duration of treatment remains an open question.

The latest study results are promising

Studies have consistently shown that the longer a man receives hormonal therapy, the better his chances for extended survival. Now, results from a phase 3 clinical trial suggest that men with locally advanced prostate cancer should get at least 2 years of additional hormonal therapy after finishing their initial combined treatment. "Our question was simply: is a short course or a long course of treatment better for the patient?" said Dr. Colleen Lawton, clinical director of radiation oncology at Milwaukee's Medical College of Wisconsin, who led the research. "And we found that the survival benefits of long-term hormonal therapy outweigh the risks."

The study, known as RTOG 9202, was launched in 1992. It enrolled approximately 1,500 men with cancer confined to both lobes of the prostate, or cancer that had spread into nearby tissues, such as the bladder. All the patients had prostate-specific antigen (PSA) levels lower than 150 nanograms per milliliter, and their Gleason scores — which describe the aggressiveness of a prostate tumor — ranged from 6 (not aggressive) to between 8 and 10 (highly aggressive). The participants' ages ranged from 43 to 88, with a median of 70 years, and the vast majority of participants were white.

During the study, half the men got only four months of hormonal therapy, starting 2 months before radiation treatment and continuing for two months during radiation treatment. The other half got that treatment plus 2 years of additional hormonal therapy.

Lawton presented the results (which have not yet been published) last November at the annual meeting of the American Society for Radiation Oncology. The data show that after a median follow-up of 20 years, men who got the long-term treatment had a 40% lower risk of the cancer spreading and a 33% lower risk of dying from prostate cancer than the men who were given hormonal therapy for just 4 months. And in a subset analysis of men with the highest-risk prostate cancer, long-term hormonal therapy dropped the odds of metastasis and death from prostate cancer even further: by 48% and 45%, respectively.

According to Lawton, the side effects of the hormonal treatment were manageable with diet, weight-bearing exercise, and drugs that boost bone density. But she emphasized that researchers are still grappling with how to define long-term hormonal therapy. As an example, she mentioned that a different study of men with locally advanced prostate cancer presented at a medical meeting in 2013 had found that disease-specific survival rates were nearly identical whether hormonal therapy lasted 18 or 36 months.

"The duration of treatment for localized prostate cancer is complicated and controversial, especially with the known cardiovascular side effects of some types of hormonal therapy," said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. "Few would argue with the view that for patients with high-risk features, such as high PSA and Gleason scores, longer is better. But we still need more clarity on the lower-risk patient populations."