Doubt Over Long-Term Use of Hormone Rx for Recurrent Prostate Cancer

Running contrary to current guidelines, new research suggests that use of hormone-suppressing treatment over the long term may not help some men battling recurrent prostate cancer, and may even cause harm.

In fact, the study found that long-term hormone therapy was tied to a raised risk of death from other causes for some patients who received it.

Blood levels of prostate-specific antigen (PSA) may help predict which men might benefit -- and which men might not -- from long-term hormone therapy following surgery, said a team led by Dr. Daniel Spratt of the University of Michigan Cancer Center, in Ann Arbor.

"We found that the lower the PSA, the more harm the patient experienced," explained Spratt, who is research professor of radiation oncology and chair of the Genitourinary Clinical Research Program at the center. "The higher the PSA, the more likely the patient was to benefit from hormone therapy because it decreased their chances of dying from prostate cancer and resulted in improved overall survival rates."

The study was presented Sunday at the annual meeting of the American Society for Radiation Oncology (ASTRO), in Chicago.

Because prostate tumors grow faster in the presence of hormones such as testosterone, therapies that lower hormone levels are often offered to men as a way to slow the cancer's spread. However, these treatments can come with side effects, such as urinary incontinence or sexual dysfunction.

Still, clinical trial results first reported in 2017 found that -- after surgical removal of the prostate tumor -- adding two years of hormone therapy, along with radiation treatment, appeared to boost patients' long-term survival.

Those findings led to the recommendation that men with recurrent prostate cancer be treated with both radiation and long-term hormone therapy after surgery.

Would those benefits last, however? To find out, Spratt's team reanalyzed data from the clinical trial of 760 prostate cancer patients that spurred the new guidelines. Men in the trial were treated at centers across North America between 1998 and 2003. All had seen their cancer return after surgery, and they received radiation therapy along with either two years of hormone-suppressing therapy called bicalutamide, or a "dummy" placebo.

Looking at the data more closely, Spratt's team found that for men with low PSA blood levels after prostate surgery, long-term hormone therapy offered no cancer survival benefit, and was associated with a doubling of the risk that these men would die from causes other than their cancer.

Patients with both low PSA and long-term hormone therapy were also three to four times more likely to experience a combination of severe heart events and neurological problems, the team reported.

"We went into this study expecting that men with low PSAs probably would derive minimal benefit from hormone therapy, but we were surprised at the magnitude of harm that these patients experienced," Spratt said in an ASTRO news release.

"A lot of these side effects have been reported over the past few decades, but demonstrating this in a clinical trial to this extent has not been done before," he noted.

"What we showed for the first time is that a patient's PSA level is a predictive biomarker," Spratt said. "That is, you can use a patient's PSA to better select which men should receive hormone therapy, and to predict who will benefit and who will not benefit from this treatment, and who may actually be harmed by it."

Spratt believes that, based on the new analysis, clinical guidelines for treating men with recurrent prostate cancer should be reconsidered.

"For post-operative patients with low PSAs, they do very well with just radiation therapy after surgery. They actually have very good long-term outcomes," Spratt said.

Two experts in prostate cancer care said decisions around hormone therapy remain tough for patients and doctors, but the new study offers a bit more clarity.

Dr. Manish Vira is vice chair of urologic research at Northwell Health's Arthur Smith Institute for Urology, in Lake Success, N.Y. He said the study "wades into the muddy waters" surrounding the risks and benefits of hormone therapy, and questions still remain.

"The results of the current study may not be generalizable to all hormonal therapy, as this study specifically used high-dose bicalutamide," he said, and other hormone-suppressing medicines might work differently.

"That being said, the study suggests that for patients undergoing radiation therapy with lower PSA values, radiation [alone] may be more prudent," Vira said.

Urologist Dr. Elizabeth Kavaler agreed.

"This is a very useful study, in that it gives clinicians clear guidelines on how to treat men with high-risk prostate cancer who have elevated PSA after surgery and radiation," said Kavaler, who practices at Lenox Hill Hospital in New York City.

"Many of these patients do very well post-treatment, and do not need further hormone therapy, which will save many of them from the side effects that hormone-deprivation causes," she added.

Because the study was presented at a medical meeting, its findings should be considered preliminary until they are published in a peer-reviewed journal.

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