NEW YORK - Hormone-targeted therapy for prostate cancer may raise the risk of potentially dangerous blood clots, a large US study suggests.
Analyzing data on more than 154,000 older men with prostate cancer, researchers found that those who received hormonal therapy had double the rate of blood clots in the veins, arteries or lungs compared to men not on the treatment.
Of the 58,000-plus men taking hormonal therapy, 15 per cent developed a blood clot over roughly four years, versus seven per cent of men who did not receive get the therapy.
A clot in the blood vessels can prove fatal if it breaks loose and travels to the lungs, heart or brain.
In this study, men who developed blood clots ended up in the hospital about one-quarter of the time, the researchers report in the journal Cancer.
"By no means is this a trivial risk," said lead author Dr. Behfar Ehdaie, of Memorial-Sloan Kettering Cancer Center in New York.
For men weighing their options for prostate cancer treatment, Ehdaie said the risk of blood clots -- and other side effects -- needs to be balanced against the benefits.
Other potential side effects of hormonal therapy include weight gain, bone thinning, hot flashes and erectile dysfunction.
And for many prostate cancer patients, experts say, the benefits of hormonal therapy are not clear.
The approach is based on the fact that testosterone can fuel the growth of prostate cancer. Curbing a man's production of the hormone -- by surgical removal of the testicles or, far more often, medication -- can be helpful.
But hormonal therapy was originally given only to men with advanced prostate cancer that had spread to other sites in the body. For them, the treatment offers symptom relief that generally outweighs the risks of side effects, said Dr. Vahakn B. Shahinian, of the University of Michigan in Ann Arbor.
Hormone therapy can also improve survival when given along with radiation therapy to men with "high-risk" prostate cancer that is likely to progress. (Many prostate tumors are slow-growing and may actually never advance to the point of threatening a man's life.)
"Those are the two scenarios where there is clear-cut evidence of a benefit," said Shahinian, who wrote an editorial published with the study. "The issue comes when you look at the host of other scenarios where hormone therapy is used."
In the past couple decades, some doctors started giving hormonal therapy as a first-line therapy to men newly diagnosed with tumors that were still confined to the prostate. That's despite the fact that the benefits for those patients are not established.
In some cases, men may be in poor health, and aggressive treatment with radiation might not be wise. But the doctor and patient may feel the need to "do something," Shahinian said. So hormonal therapy is the choice.
There's also evidence that financial motives have played a part, Ehdaie noted.
By 1999, hormonal therapy was given to about half of prostate cancer patients. But studies have found that after more recent cuts in Medicare reimbursement for the therapy, fewer doctors are using it.
The bottom line, both Ehdaie and Shahinian said, is that men should thoroughly discuss the risks and benefits of different prostate cancer treatments with their doctor.
As for why hormonal therapy would promote blood clots, the mechanisms are uncertain.
In fact, the current findings do not prove that the therapy itself is the direct cause of men's blood clots. Ehdaie's team tried to account for other factors that could explain the link; and they did find that men on hormonal therapy tended to be older and in poorer overall health.
But even with those differences considered, men on hormonal therapy had a 56 per cent greater chance of developing a blood clot. And the clot risk generally climbed the longer a man was on the treatment.
"We can't infer causality, but it is a strong association," Ehdaie said.
It's possible, he noted, that hormonal therapy raises the risk of clots because of its negative effects on metabolism, which can include boosting a man's fat mass.
"I think the take-away message is that this reinforces the fact that hormonal therapy has potential risks, and men should be informed," Shahinian said.
Shahinian is a paid consultant to Amgen, which is seeking approval for its bone cancer drug, Xgeva, to treat certain men with advanced prostate cancer.
For many men with prostate cancer, having no immediate treatment at all is an option.
According to the National Cancer Institute, about half of the more than 190,000 US men diagnosed with prostate cancer in 2009 fell into the "low-risk" category -- meaning their cancer had low odds of progression.
They are among the men who can choose to forgo treatment and instead have their cancer monitored -- what doctors call "active surveillance."
Such watchful waiting can be stressful, Shahinian noted. But men should be aware that "doing something" comes with potential risks, he said.