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.

And what if - as may be the case with prostate cancer -- the benefits of quicker diagnosis and treatment are concentrated among relatively few people, whereas the costs, perhaps much larger, are spread over many more?

Yang is one of these critics. "It's gone out of control," he says. "People don't know what they're doing, and it's going to be a terrible mess. I feel sick about it. It's a disaster for the healthcare system - a horrible disaster. We've rushed ahead and created a nightmare."

The Troublesome Gland

At the center of the dispute is the prostate, a small gland that is frequently burdened in description with adjectives like "obscure," "inessential," and "dumb." Prostates vary considerably in size from man to man, but typical examples are said to be about the size of a walnut and to weigh almost an ounce. They are solid, as opposed to spongy, and are loosely attached to the bottom of the bladder. Their job is to concoct a chemical stew - PSA is one of the ingredients - and add it to semen just before ejaculation. Nobody understands what, precisely, the added compounds do, but they are thought to be important in reproduction.

From an evolutionary point of view, there is little reason for the prostate to keep functioning after the typical age of reproduction - and it doesn't. Indeed, the number of men who escape prostate trouble of any sort is small enough to put the likelihood of experiencing it just below that of death and taxes. No one knows why, though every researcher I have asked has a laundry list of speculations. "Perhaps it is exposed to carcinogens," says Donna Peehl, a specialist in prostate genetics at the Stanford University School of Medicine. "Perhaps the problem is its proximity to the urethra the channel carrying urine from the bladder], with all that urine leaking through. That explanation doesn't work particularly well, though. Perhaps it's a developmental thing, something about the biology of the prostate that is important to its normal behavior but that we don't know yet." Nobody knows, she says. "It's kind of an obscure little gland and yet it causes all this trouble."

The trouble comes in three varieties: prostatitis; benign prostatic hyperplasia (BPH); and prostatic carcinomaprostate cancer. All are diseases of old age, or at least middle age. Prostatitis is simply an infection or inflammation of the prostate. It is extremely common. Indeed, many men have chronic cases that they don't know about and don't need to know about, because the disease poses no longterm threat and in those men has no noticeable effects. In bad cases symptoms occur during urination: a sensation of burning, a need to urinate more often or more urgently than usual, or an inability to release more than a small amount of urine. The standard treatment is antibiotics of a class known as fluoroquinolones; the most common is ciprofloxacin (made by Miles, and sold as Cipro). A successful outcome is taken for granted.

Benign prostatic hyperplasia occurs when the inner portion of the prostate enlarges. The urethra tunnels through the middle of the prostate like a string through a bead. When the prostate swells, it becomes, in effect, a choke collar for the urethra, obstructing the flow of urine. Actually, it becomes a second collar; a band of muscle, the urethral sphincter, already rings one end of the prostate, preventing unwanted urination. That sphincter is under voluntary control; the BPHcaused sphincter is not. Symptoms of BPH include both trouble with urination and, paradoxically, its opposite, trouble with holding back urination, especially at night. By age sixtyfive about three quarters of all men will experience BPH - indeed, that is when some men first learn they own a prostate. The cause of BPH is unknown. It just seems to happen, along with wrinkles, hair on the shoulders and in the ears, and the other irritants of male aging.

BPH is "benign" only as doctors understand the word, which is to say that it is not malignant. ("Hyperplasia" is the unwanted growth of tissue.) It is almost always a bother and sometimes more than that, leading to infections of the urinary tract. If the symptoms are unpleasant enough, doctors recommend treatment. Until recently the most common treatment was transurethral resection of the prostate, or TURP. The surgeon threads a fiberoptic tube through the penis to the prostate, guided by a light at the tip of the tube. Bits of tissue bulge into a hole in the side of the tube, where they are snipped off by a tiny blade and sucked away. Repeated clippings eventually free up the passage. Descriptions of the procedure often include references to "RotoRootering." According to Patrick Walsh, the chairman of the urology department at the Johns Hopkins University School of Medicine, TURP is usually effective, although like all surgery, it is expensivethe full tab often runs to more than $5,000. Longterm difficulties with urinary control continue for about one out of every hundred patients, and fewer than one out of twenty, Walsh says, have subsequent problems with impotence.

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).

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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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