TORONTO – Men with prostate cancer that has spread to local surrounding tissues live longer and are less likely to die of the high-risk disease if treated with a combination of radiation and hormone therapy, rather than with the drug treatment alone, a study has found.
The finding could change the standard for treating this aggressive form of prostate cancer, which represents about one in five cases of the disease, said Dr. Padraig Warde, a radiation oncologist at Princess Margaret Hospital in Toronto who led the international study.
“The study shows combining radiation and hormone therapy improves overall survival by 23 per cent and disease-specific survival by 43 per cent, compared with treating with hormone therapy alone,” said Warde.
To conduct the study, 1,205 men with locally advanced prostate cancer in Canada, the U.S. and the U.K. were randomly divided into two groups. Half received androgen-deprivation therapy to suppress testosterone production, while the other half were treated with the hormone therapy plus radiation.
After seven years, 66 per cent of men who had the hormone therapy alone were still alive, compared with 74 per cent who received the combination treatment. Among those in the hormone treatment-only group, 26 per cent died from their prostate cancer, compared with 10 per cent who received both therapies.
“The two of them together combined are the important thing,” said Warde. “You can’t use radiation alone. What it’s showing is that radiation plus hormones are better than hormones alone.”
Androgen deprivation therapy, given by intramuscular injection, works by starving prostate cancer cells of testosterone, which they need to multiply. The treatment also makes cancer cells more sensitive to the killing effects of radiation, Warde explained.
This year, an estimated 25,500 men in Canada will be diagnosed with cancer of the walnut-sided gland, and about 4,100 will die of the disease. About 15 to 20 per cent of cases are the aggressive or high-risk type with localized spread.
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“And these are the bad actors,” said Warde of this form of the cancer. “These are the patients, if you look overall, who die of prostate cancer, whereas many of the people who present with earlier-stage disease, they actually will live very long even with or without treatment. They don’t die of prostate cancer – they die with it.
“But with these ones, a lot of the patients will die of prostate cancer.”
The study is published in the Nov. 2 issue of The Lancet, and Warde believes its findings will alter the practice of using just hormone therapy for locally advanced prostate cancer.
“There is substantial evidence that many, many patients … are treated with hormone therapy alone and are never referred for consideration of (radiation) treatment,” he said. “So they’re never given the chance of cure because with locally advanced disease, many urologists in particular – although I’m not picking on them – believed that this is incurable cancer and there was really no point in giving them additional treatment beyond hormones.”
The international research team enrolled and treated patients over 10 years beginning in 1995, and Warde said the radiation therapy used was typically “old-style” – employing lower doses of radiation in less finely targeted beams, compared with treatment today.
“So, in fact, there’s every reason to believe that with the radiation we use now … that the results are likely to be much better because we hopefully kill more cancer cells with the radiation and we’re much more precise now,” he said.
Some side-effects can occur, however, including damage to surrounding tissues like the rectum and bladder, which can cause tenderness, some bleeding and diarrhea. Warde said these effects are most pronounced in the first six to 12 months on average, but don’t seem to persist beyond three years following treatment.
Still, he believes that adding the radiation component will lead to a better outcome for many patients.
“It’s practice-changing in that we will be getting out to patients, physicians across North America and Europe … that actually these patients should no longer be treated with hormone therapy alone. They should be referred for consideration of radiation, and hopefully many of them will benefit and live longer and more productive lives.”
Dr. Martin Gleave, director of the Vancouver Prostate Centre, does not see the study so much as a “game-changer,” but a confirmation of what cancer specialists have surmised for some time.
“The fact that adding radiation helps survival affirms our biases,” Gleave, a professor of urology at the University of British Columbia, said from Vancouver. “But on top of that, I think it will lead us in the future towards being more aggressive in managing the local disease.”
“Where we would have thought, or at least hypothesized, that maybe the horse is out of the barn and closing the barn door doesn’t make a difference … (the study suggests that) closing the barn door and preventing more horses from getting out does make a difference,” he said of the double-barrelled treatment to halt the migration of cancer cells.
Gleave said more aggressive treatment could mean using chemotherapy along with hormone-suppression and radiation, a triple combination that Warde’s team has already begun testing. Surgery might also be included in such a treatment regimen, Gleave added.
Dr. Michael Wosnick, vice-president of research for the Canadian Cancer Society, said the study’s results should change how doctors approach the treatment of this type of prostate cancer.
“It should certainly, at least, be an option for physicians to discuss with their patients about the benefit of having both (hormone and radiation therapy),” Wosnick said Wednesday. “It seems pretty clear that this absolutely should be an option that men should be presented with.”
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