Men whose prostate cancer comes back after surgery are more likely to survive if, along with the usual radiation, they also take drugs to block male hormones.
After surgery to remove the prostate, more than 30 percent of men have a recurrence, and until now there has not been clear evidence about the best way to stop the disease from killing them. Most are given radiation, but prescribing drugs to counter the effects of male hormones has been inconsistent.
The study, paid for by the National Cancer Institute, showed that among men who received radiation and hormonal treatment, 76.3 percent were still alive after 12 years, compared to 71.3 percent who had radiation alone.
At 12 years, the men who had both treatments were also much less likely to have died from their prostate cancer — 5.8 percent versus 13.4 percent — or to have the cancer spread around their bodies — 14.5 percent versus 23 percent.
“This is a big deal,” said Dr. Ian M. Thompson Jr., of the Christus Santa Rosa Health System in San Antonio, who was not part of the study but wrote an editorial accompanying it.
“There are so many things we do in prostate cancer that we don’t know if they make a big difference in survival. This is one of the things where now we can say for sure.”
He added that he hoped the findings would change medical practice.
The medical term for blocking male hormones is chemical castration, and the treatments can cause hot flashes, sexual problems and other side effects. So to put a man through it, said Dr. Anthony L. Zietman, an author of the study, “you’d better have some decent justification.”
Dr. David F. Penson, the chairman of urologic surgery at Vanderbilt University Medical Center, said the study “gives more credence to the concept that you have to treat the whole patient,” rather than just irradiating the area where the cancer used to be.
He said the idea of blocking hormones in men like those in the study was finding its way into medical practice.
About 161,360 new cases of prostate cancer and 26,730 deaths are expected in the United States in 2017, according to the American Cancer Society.
The average age at diagnosis is 66. Globally, there were 1.1 million cases and 307,000 deaths in 2012, the most recent data available from the World Health Organization.
The study, begun in 1998 and led by Dr. William U. Shipley, a radiation oncologist at the Massachusetts General Hospital, had an ambitious goal: to follow the patients long enough to find out whether hormone-blocking treatment would affect their survival.
Prostate cancer grows slowly, so it took well over a decade for answers to emerge. Researchers and patients from 150 sites in North America participated. The patients were 760 men who had their prostates removed for cancer that had not spread, but who then had a sign of recurrence — a rise in their blood levels of prostate-specific antigen, or PSA, a protein associated with prostate cancer. The men in the study had PSAs of 0.2 to 4 nanograms per milliliter.
“That’s just like the first wisp of smoke,” said Dr. Zietman, who is a professor of radiation oncology at Massachusetts General Hospital and Harvard Medical School. “There’ll be fire someday.”
The fire might take five, 10 or 15 years to break out, but Dr. Zietman said, “Many are in their 50s or 60s, and will live long enough to get into trouble.”
The traditional practice for a rising PSA after surgery has been to give radiation, which targets only the pelvis.
The idea of the study was to add hormonal treatment, which might stop minute clumps of cancer that had spread to other parts of the body.
All the men in the study had radiation for six and a half weeks. For two years, half also received a hormone-blocking drug, bicalutamide, and the other half were given placebos. They were followed, on average, for about 13 years.
“This is the first trial that’s shown, if you follow these patients long enough, there is a real difference,” Dr. Zietman said. “More people survive 15 years later.”
Men who had more aggressive cancers — reflected by higher PSA readings after surgery and by the pathology and surgical reports on their tumors — had the most to gain from the hormone-blocking treatment.
The results do not mean that every man with a rising PSA after surgery should have hormone treatment, Dr. Zietman said. Men 75 or older may not need it, because they may die from other causes before the cancer can catch up with them.
“But if they’re younger and with a longer life expectancy, treatment is reasonable,” he said.
Bicalutamide causes men to develop breasts and potentially other problems, and the high dose given in the study is no longer used in the United States.
Other hormone-blocking drugs like Lupron have mostly taken its place, and may be even more effective, Dr. Zietman said. The study proved the concept that hormone blocking increases survival, he added, so other drugs that do the same thing should also help patients live longer.
Another study in progress in Canada and Europe uses the newer drugs, and is trying to determine whether taking them for six months, rather than two years, might be enough.