When prostate cancer recurs after surgery, treatment with both radiation and a testosterone-suppressing drug can extend some men’s lives, a new clinical trial finds.
In a nearly 20-year study, researchers found that the combination therapy cut the risk of death from prostate cancer in half, compared to radiation alone.
And that translated into better overall survival, the researchers reported in the Feb. 2 New England Journal of Medicine.
After 12 years, just over 76 percent of men who’d received radiation and the hormonal drug bicalutamide (Casodex) were still alive. That compared with just over 71 percent of those who’d received radiation alone.
Not all patients benefited from extra treatment, though — including those with “lower-risk” prostate cancer that, despite recurring, appeared less aggressive.
And the testosterone-blocking drug carried expected side effects, such as enlarged breasts.
But on balance, the findings should be “practice-changing,” said senior researcher Dr. William Shipley, of Massachusetts General Hospital in Boston.
The trial was funded by the U.S. National Cancer Institute (NCI) and AstraZeneca, which makes Casodex.
Other prostate cancer experts said the results offer “important” information. But they also said it’s unclear how the findings will affect current prostate cancer treatment.
Since this trial began in 1998, “the prostate cancer therapeutic landscape has changed,” said Dr. Alexander Kutikov, an associate professor of urologic oncology at Fox Chase Cancer Center in Philadelphia.
For one, Kutikov said, bicalutamide has been largely replaced by newer hormonal medications. Known as gonadotropin-releasing hormone agonists, they include drugs such as leuprolide (Eligard, Lupron) and goserelin (Zoladex).
And the newer medications, along with radiation, are already offered to some men with recurrent prostate cancer, said Dr. Ashutosh Tewari. He’s chair of urology at Mount Sinai’s Icahn School of Medicine in New York City.
Other ongoing trials are looking at those therapies, researchers said. One tested the effects of adding goserelin to radiation therapy in men with early signs of prostate cancer recurrence.
So far, that study has found that the combination keeps more men progression-free over five years. And the duration of the hormone therapy was much shorter, versus the bicalutamide trial: three months, rather than two years.
Plus, Kutikov said, when today’s hormonal drugs are used with radiation as an initial therapy — not for a recurrence — six months of hormonal treatment has “proven to be sufficient” for many men.
“As such,” Kutikov said, “the study’s findings will need to be reconciled with current clinical practice.”
Still, the bicalutamide trial is the only one that has gone on long enough to show that adding hormonal therapy to radiation can actually extend the lives of some men with biochemical recurrences.
A biochemical recurrence means their levels of prostate-specific antigen (PSA) start to rise again — an early sign that the cancer may be returning.
Prostate cancer usually progresses slowly, so it took more than a decade to see a survival advantage with bicalutamide, the researchers said.
According to Tewari, the study offers “proof-of-principle” that adding “something to radiation is better than radiation alone.”
Roughly 181,000 U.S. men were diagnosed with prostate cancer in 2016, according to estimates from the NCI.
Because the disease is typically slow-growing, most men are diagnosed when the tumor is confined to the prostate gland, according to the NCI.
Many patients have the option of delaying treatment and going with “active surveillance” — where doctors closely monitor the cancer for signs of progression.
But in the United States, studies show that most men choose treatment. That treatment typically involves surgery to remove the prostate. Of men who undergo surgery, more than 30 percent will have a biochemical recurrence, according to Shipley’s team.
Shipley and his colleagues studied 760 men who’d undergone surgery for localized prostate cancer and later had a biochemical recurrence.
They randomly assigned the patients to take either bicalutamide or placebo pills every day for two years. All of the men underwent 6.5 weeks of radiation.
After 12 years, almost 6 percent of bicalutamide patients had died of prostate cancer, versus just over 13 percent of placebo patients.
The benefits were not uniform, though, Kutikov pointed out.
Hormonal therapy made no difference in the survival rates of men with relatively low PSA levels when they entered the trial (below 0.7). The same was true of men with “Gleason scores” below 7.
That score is based on what a tumor sample looks like under the microscope. A lower score means the cells look more “normal,” and the cancer is less likely to progress.
That, Kutikov said, suggests that men with lower-risk cancer could be “overtreated” if they receive hormonal therapy.
Overtreatment is a worry because it needlessly exposes patients to the risk of side effects.
In the case of hormonal therapies in general, Kutikov said, the potential side effects include lost libido and erectile dysfunction.
The American Cancer Society has a guide on prostate cancer treatment.