The Prostate Cancer Dilemma

The country is embarking on a huge screening program for prostate cancer which is likely to cost billions and may lead to many unnecessary operations, especially for elderly patients. But what may be bad at the national-policy level could be a lifesaver at the individual level for men in their fifties and early sixties.

One out of twenty sounds better to doctors than to patients, especially when it refers to sexual ability. Impotence and incontinence can usually be alleviated by further surgery, but for obvious reasons research into alternatives - that is, drugs - is vigorous. Unfortunately, BPH is linked to the presence of male hormones, especially testosterone, and male hormones are necessary to maintain interest in sex. Past efforts to treat the condition without surgery involved blocking the effects of testosterone, which risked eliminating a man's libido. Only recently was it discovered that not testosterone itself but rather some of the substances into which it is transformed by the prostate are directly responsible for BPH. First to take advantage of this finding was Merck & Company, a huge pharmaceutical firm that last year received FDA approval to market finasteride under the brand name Proscar. Finasteride blocks the action of 5-alphareductase, a compound secreted by the prostate which converts testosterone to dihydrotestosterone, one of the hormones that stimulates prostate growth. Like TURP, Proscar at least temporarily affects the sexual activity of some men, in this case about one out of twentyfive. Unlike surgery, though, its negative effects can be reversed easily - by throwing out the bottle of Proscar. From the point of view of a drug maker, Proscar is an ideal product: it costs more than $50 a month and must be taken forever. Unsurprisingly, Merck has widely advertised it in newspapers and magazines, including this one, though without mentioning Proscar by name.

Whether Proscar helps a particular man may depend on the makeup of his prostate. Dihydrotestosterone seems to affect the soft glandular part of the prostate to a greater degree than the hard muscular part. If a man's prostate is more glandular than muscular, he may be more likely to be helped. If it is the other way around, those men may need a TURP or perhaps some other, new treatment. One possibility for the latter is the class of drugs called alpha adrenergic blockers, which people with high blood pressure take to relax bloodvessel walls. The muscle in the prostate is similar to the muscle in blood vessels, and Patrick Walsh and others have told me that the analogy is promising. Alpha blockers have not been approved by the FDA for this purpose, but many doctors are already prescribing them on the basis of preliminary reports; among the most common is terazosin (brand name Hytrin, made by Abbott).

The third and most serious problem is prostate cancer, a medical oddity that is a long way from being understood. If all men lived to be ninety, almost all would harbor prostate cancer. It is especially widespread among African-Americans, who have the highest rates of death from prostate cancer in the world. According to John T. Isaacs, a medical oncologist at Johns Hopkins, data from autopsies suggest that about 11 million Americans have prostate cancer in some form. Lung cancer is thought to afflict about 300,000 Americans. The disparity in the prevalence of different types of cancer is baffling, and especially so when comparing prostate cancer with other kinds. "Cancer of the colon is extraordinarily common," says John McNeal, a pathologist in the department of urology at Stanford, "whereas cancer of the small intestine is very uncommon. How come? Here's two parts of the same organ, hooked together, and one appears to be quite susceptible to cancer and the other appears not to be." Yet more puzzling, he says, is the seminal vesicle, the small gland that produces most of the constituents of seminal fluid. "The seminal vesicle is attached to the prostate, and cancer of the seminal vesicle is, I would guess, the rarest of all human cancers, and it's only millimeters away from the organ that has one of the commonest cancers."

The American Cancer Society projects that no more than 165,000 prostate carcinomas will be discovered this year, whereas it expects 170,000 new cases of lung cancer and 182,000 of breast cancer. The difference is due in part to the relative newness of the PSA test, which for the first time makes diagnosis likely. But more important is the propensity for this cancer to lurk for years or even decades without apparent ill effects. As a rule it grows extremely slowly, taking four years or more to double in size. Breast carcinomas, in contrast, often double in less than three months; a tumor the size of a pinprick will fill a cubic centimeter in a couple of years and be ready to spread. According to McNeal, only about one out of five prostate carcinomas ever becomes clinically significant. The rest are sometimes called histologic carcinomas, meaning that tissue at the disease site fits the technical definition of cancer but no more. Many histologic carcinomas are microscopic; some are barely distinguishable from their surroundings. In some sense, he says, this dormancy is what one would expect. "A cancer so common as this would have to be very slowgrowing or it would have wiped out the population at the upper end," he points out. "It would not be something that people are just becoming aware of if it were like other cancers."

At present no one can distinguish at the outset between those carcinomas that will cause no trouble in a man's lifetime and thus should be ignored and those that will spread in time and thus should be treated, if at all possible. Scientists are not likely to solve this quandary in the near future. Cancer cells are generally thought to be created by a sequence of genetic mishaps. Every time a cell divides, there is a tiny chance -- typically one in a billion - that it will not copy its genetic material precisely and will instead produce a slightly abnormal daughter cell. (Such failures occur randomly, although their incidence can be increased by exposing the body to carcinogens, chemical compounds that in some way interfere with cell division.) In turn this imperfect daughter cell divides. There is a slight probability that it, too, will fail to copy itself exactly - actually, a slightly greater probability, because precancerous cells seem to be accidentprone. If the cell makes the "right" error, it will be one step further toward full malignancy. In colon cancer the mistakes usually occur in sequence. In prostate cancer, though, each mistake may be independent of the others, so that, say, step No. 4 could occur before step No. 2 and after step No. 6. All that matters is that over the years one cell or set of cells passes through every step. Nobody knows why this happens to one man rather than another, or why it happens especially often to AfricanAmericans.

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Charles C. Mann, an Atlantic contributing editor, has been writing for the magazine since 1984. His recent books include 1491, based on his March 2002 cover story, and 1493.

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