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http://www.nytimes.com/2002/09/12/health/12PROS.html?tntemail0

Prostate Cancer Surgery Found to Cut Death Risk

By GINA KOLATA

or the first time, scientists have shown in a rigorous study that surgery to remove a cancerous prostate gland can reduce the risk of death from the disease.

About a third of the 189,000 American men who are newly diagnosed with prostate cancer each year choose to have their prostates removed, said Dr. Patrick Walsh, director of the Brady Urological Institute at Johns Hopkins Hospital. But until now, Dr. Walsh said, doctors could offer no proof that the operation affected the course of the cancer, because it can progress so quickly — or slowly — that surgery might be useless.

"There was all this, `We don't know,' " Dr. Walsh said. "There was all this uncertainty. It was crazy for men."

The new study changes all that, he added.

Others agreed.

"It's going to be a landmark study," said Dr. Otis Brawley, the associate director for cancer control at the Winship Cancer Institute of Emory University. "It's really the first that shows that radical prostatectomy does something positive."

But while the study, in Sweden, was large, with 695 men ages 60 to 70, and done according to the strictest scientific design, its patients were not exactly like the typical prostate cancer patient in the United States today.

The Swedish men generally discovered that they had prostate cancer because the tumors had grown large enough to cause symptoms, like difficulty urinating. In the United States, most men find out they have prostate cancer when they have a screening test, the P.S.A., or prostate specific antigen, that looks for a protein in the blood that can be indicative of a cancer too small to feel. It is not certain whether surgery for cancers that small would be better, or worse, than it was for the larger tumors.

But the study, published today in The New England Journal of Medicine, resolved a thorny issue. Until now, some doctors had argued that the popular cancer surgery might not stop the disease from spreading. It was possible, they argued, that aggressive cancers that could kill had already spread beyond the prostate by the time they were detected, making the operation futile, while the less aggressive ones would never spread in a man's lifetime, making the operation unnecessary.

The way to answer that question was to randomly assign men to be treated, with the surgery, or to forgo treatment unless and until the cancer spread in their body. The Swedish investigators found that after an average of 6.2 years of follow-up, 16 of the 347 men who had surgery died of prostate cancer, or 4.6 percent. But 31 of the 348 who were assigned to watchful waiting died of prostate cancer, or 8.9 percent, a statistically significant difference.

The researchers calculated that 17 men would have to have the operation to prevent one death from prostate cancer over an eight-year period.

The study did not include other popular prostate cancer treatments, for example, external beam radiation, which is directed at a man's prostate, or radioactive seeds, which are implanted in the prostate. Although doctors assume that the treatments are more or less equivalent to prostate surgery, that has not been rigorously demonstrated, nor has it been shown that these treatments prevent prostate cancer deaths.

Yet while the prostate cancer death rate was reduced in the Swedish study, the overall death rate from all causes, including prostate cancer, was not. Fifty-three men who had surgery died, as against 62 men in the watchful-waiting group, a statistically insignificance difference.

The study's principle investigator, Dr. Lars Holmberg of University Hospital in Uppsala, said he was not surprised because there were so many other possible causes of death in men in that age group. While prostate cancer is the second leading cause of cancer deaths in this country, it is but one of many reasons men of that age might die. To make an impact on the overall death rate, there would have to be a much greater decline in the prostate cancer death rate than occurred in this study.

"In this age group, the competing risks for death are so large that deaths from prostate cancer would vanish in the noise," Dr. Holmberg said in a telephone interview.

In their paper, the researchers suggested another possible reason that the overall death rate was not lower. Men who had surgery might die at a higher rate from causes other than prostate cancer because of "hitherto unknown adverse effects of prostatectomy," they wrote. For example, medical experts said, a man who had a prostate operation might develop blood clots that killed him with a stroke the next month.

The Swedish investigators also questioned the men about their quality of life and found that those who had the surgery were more likely to be impotent, 80 percent, as compared to 45 percent who had watchful waiting. They also were more likely to be incontinent. But they were less likely to complain that it was difficult to urinate. The men in both groups had similar assessments of the overall quality of their lives.

When it comes to men with very tiny tumors, found by P.S.A. screening, doctors say that the operation could reduce the death rate from prostate cancer either more or less than in the Swedish study. The test finds tumors five to seven years before they would cause symptoms, leaving men an extra five to seven years to live with the possible surgical side effects, like impotence and incontinence. Dr. Michael Barry, who is chief of the general medicine unit at the Massachusetts General Hospital, said that some tumors detected by screening are so small and grow so slowly that they are found only on autopsy, so men die with them, not of them.

But it is also possible, Dr. Barry said, that the men with very early cancers will reap a greater benefit from the surgery. Most men in the Swedish study did not have P.S.A. screening and, with their cancers found later, they may have spread outside the prostate, invisibly seeding themselves in the bone by the time they began causing symptoms. In that event, removing the prostate would have been futile, although the doctors would not have known it because they had not detected the cancer's microscopic spread.

Dr. Walsh said that reducing deaths from prostate cancer is overwhelmingly important, even if the overall death rate did not budge. "If you've ever seen anyone die from prostate cancer, it's a terrible death," he said, explaining that the cancer tends to spread to the bones, making them break. Others said they would like to see a reduction in the overall death rate, especially in men having the operation years before they have symptoms.

Some answers should emerge from a study, now under way, sponsored by the Department of Veterans Affairs, the National Cancer Institute, and the Agency of Health Research and Quality. It includes 731 men, mostly veterans, with localized prostate cancer, usually found by a P.S.A. test. Half were randomly assigned to have a their prostates removed and the rest to watchful waiting. The study is to continue until 2008 unless a clear survival advantage emerges for either the surgery or watchful waiting.

So far, five years into the study, no such advantage has appeared, said Dr. Timothy J. Wilt of the Minneapolis V.A. Medical Center.

"I would like to conclude that while the Swedish study is a very important piece of information, when put into context, the preferred treatment for prostate cancer still is not known," Dr. Wilt said.

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