Study Compares Timing of Hormonal Therapy for Prostate Cancer

Men with metastatic prostate cancer who undergo hormone-deprivation therapy sometimes take breaks from the treatment to minimize its often difficult side effects.

However, a major new study that tracked more than 1,500 men for almost a decade finds that opting for intermittent treatment may take a toll on certain patients, in terms of shortened survival.

The study found that for men with cancer involving “minimal spread,” adopting a stop-and-start treatment schedule was associated with a two-year decline in survival compared to men who’d been treated on a continuous basis.

This gap in survival did not appear for men whose prostate tumors showed more extensive spread, but the researchers stopped short of recommending intermittent treatment for this subset of patients, pending better data.

The study, funded by the U.S. National Cancer Institute, was reported Sunday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

According to the American Cancer Society, prostate cancer is the second most common cancer in men after skin cancer, with almost 242,000 new cases diagnosed in the United States each year.

Doctors have long known that prostate tumors “feed” on circulating male hormones such as testosterone. So hormonal deprivation therapy – designed to turn off testosterone production and thereby stop cancer growth – remains a common first-line approach in keeping the cancer at bay.

But, there’s a big downside to the treatment, since it “is associated with significant side effects, including loss of libido, erectile dysfunction, osteoporosis, muscle wasting, hot flashes, depression and cardiovascular issues,” said Dr. Herbert Lepor, chairman of the department of urology at New York University School of Medicine in New York City.

He said that in prior studies, “intermittent therapy was equally effective as continuous therapy with fewer side effects,” and so patients have sometimes opted for this approach.

But, would the intermittent approach remain equally effective over the long term?

The new phase 3 trial sought to answer that question. In the study, researchers tracked outcomes for more than 1,500 men with hormone-sensitive cancers that had spread beyond the prostate. All of the men first got seven months of continuous hormone deprivation therapy. Then, half were randomly chosen for intermittent treatments while the other half stayed on the continuous regimen.

Overall, the men who got the stop-and-start treatment were exposed to about half the total amount of hormonal therapy as the men in the continuous group, the researchers said.

Unfortunately, “survival with intermittent hormone therapy was inferior to survival with continuous hormone therapy,” reported study author Dr. Maha Hussain, a professor of medicine and urology at the University of Michigan Comprehensive Cancer Center.

Speaking at an ASCO press briefing, she concluded that “because of these findings, continuous therapy continues to be the standard of care.”

After a median follow-up of more than nine years, overall survival in men with minimal disease spread (no cancer beyond the spine, pelvis and lymph nodes) was 7.1 years for those on continuous therapy vs. 5.2 years for those treated intermittently – a two-year difference.

That gap in survival closed for men with more extensive disease (4.4 years for those on continuous therapy vs. 5 years for those in the intermittent group). However, Hussain was careful not to recommend treatments breaks, even for this sicker group of patients, saying that the finding was “surprising” and more data is needed.

For patients with extensive cancer spread, it’s best to discuss treatment options with a doctor before embarking on either one of the regimens, she said.

Dr. Bruce Roth, a professor of medicine in the division of oncology at Washington University School of Medicine in St. Louis, said experts had waited a long time for the findings of this “important” trial.

“Prior, underpowered studies suggested that there was no downside to intermittent therapy, which clearly provides less toxicity,” he said at the press briefing. “This study for the first time indicates that there is a price to pay.”

Lepor agreed that, “on the basis of this study, intermittent androgen [hormonal] deprivation therapy should no longer be recommended for those men with minimal disease spread.”

Findings presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.

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By E.J. Mundell
HealthDay Reporter