Originally created 05/17/99

Cells give doctors early warning of prostate cancer



ATLANTA -- Looking for cells at the earliest stage of going bad may help doctors identify still-healthy men who are at high risk of developing prostate cancer, the most common male malignancy.

Doctors say that checking for these precancerous cells could offer the male equivalent of the Pap test, the routine screening that identifies cervical cancer in its curable early stage.

The precancerous growths are called high-grade PIN, short for prostatic intraepithelial neoplasia. Though experts have suspected for more than a decade that this is cancer in the making, a study released Sunday is the first to show what happens to men with these cells.

The research, conducted among military veterans in Boston, found that older men with high-grade PIN have a 50-50 chance of developing prostate cancer, double the usual risk.

Still doctors are unsure what to do with this information. There is no good evidence yet that taking out these men's prostate glands will ward off death from cancer, although this is possible.

"High-grade PIN definitely predicts for a high risk of prostate cancer," said Dr. Christopher Nauman of Boston University School of Medicine. "We have to watch them very closely."

Dr. Nauman presented his findings at a meeting in Atlanta of the American Society of Clinical Oncology.

His team reviewed the outcome of men who underwent prostate biopsies between 1989 and 1993 because blood tests hinted at possible cancer or doctors felt lumps in their prostates. Sixty-one had high-grade PIN, while 47 did not.

After seven years of follow-up, prostate cancer was found in 49 percent with high-grade PIN, compared with 21 percent of the other men.

There were too few cancer deaths in either group to show whether knowing men's PIN status improved their chances of survival.

Because the men were relatively old -- their average age was 69 -- doctors did nothing beyond watch them closely. Doctors often are reluctant to operate on older prostate patients, because they may die of something else before slow-growing prostate tumors cause serious problems.

Nevertheless, prostate cancer is the leading malignancy among men, and it trails only lung cancer as a cancer killer. This year, doctors will diagnose about 180,000 cases.

Because of routine PSA -- prostate-specific antigen -- testing, doctors increasingly are finding prostate cancer in men in their 50s. At that age, more aggressive treatment may be worthwhile to catch the cancer before it escapes the prostate gland.

"This study is important, because if you find PIN in a young man, you have to be very suspicious that he will soon have cancer," said Dr. Deborah Kuban of Eastern Virginia Medical School in Norfolk.

Doctors recommend that men with high-grade PIN undergo repeat biopsies every three to six months.

While doctors compare high-grade PIN to the pre-cancerous stages of cervical cancer, there are significant differences: Checking for cervical cancer involves a simple Pap test, which examines cells swabbed from the surface of the cervix. Looking for PIN is much more difficult, because it requires sticking a needle into the prostate to extract cells for examination.

Early detection of prostate cancer is especially important, because the cancer can be cured only if treated before it has spread. However, researchers are examining new strategies intended to stop the disease by harnessing the body's immune and genetic defenses.

A variety of genetic errors cause prostate cancer. Among them are malfunctioning p53, a gene that ordinarily triggers cancerous cells to commit suicide, and overproduction by a gene that makes Her2, a protein that prompts cells to divide.

At Sunday's session, Dr. Christopher Logothetis of M.D. Anderson Cancer Center in Houston described preliminary results of an attempt to improve the results of prostate surgery by injecting the gland first with a virus that carries in good copies of the p53 gene.

In a study on 26 men, he showed that this approach made the tumors shrink, possibly improving the chances that prostate-removal surgery will be more effective.

In another approach, Dr. Nicholas James of the University of Birmingham in England tested a hybrid antibody that targets the Her2 gene. In 25 men with spreading cancer, it lowered blood signs of malignancy and eased pain. The treatment is similar to Herceptin, a newly approved drug being used against breast cancer.