The genetic material in a cell is deoxyribonucleic acid, or DNA, long, threadlike molecules twisted into forty-six bodies called chromosomes, which resemble the soft Hs in alphabet soup. Failures take place either when entire chunks of a chromosome snap off, fall away, or switch places, or when small bits of the strand get lost or mixed up. The former are easier to spot than the latter. For example, cancer of the colon is associated with gross chromosomal abnormalities, one reason that scientists have recently nailed down the sequence of events that leads to it. No such obvious changes have been spotted in prostatecancer cells, and hence the thinking is that the accidents involved are small and affect individual bits of DNA. If it were stretched out, the DNA in each human cell would be about six feet long; errors may involve snippets shorter than a millionth of an inch. The implication for researchers, unpleasant to contemplate, is a long period of slogging. Thus far the only clue is the possibility, turned up over the past three years by a group of researchers in Sweden and a second group at Johns Hopkins led by John Isaacs's brother William, that particular bits of chromosomes 8, 10, and 16 may be involved. Is a sudden clinical breakthrough possible? William Isaacs thinks it unlikely. "No one is going to shout 'Eureka!' on this one," he says. "The champagne is safe."
Imagine a blindfolded man with an unlimited supply of darts. He is standing before, say, six dart boards. (The exact number of steps necessary for prostate cancer to occur is unknown; colon cancer, as it happens, involves six major chromosomal changes, so I chose that number.) Blindly tossing away, he will eventually hit a bull'seye. That is equivalent to one of the "right" genetic accidents. After, say, two or more bull'seyes he will have histological cancer. After a long time he will probably hit all six bull'seyes. When he does, the cancer will be fully developed and ready to spread. The question is when treatment should occur. Surgery for prostate cancer involves the possibility of impotence, incontinence, and death. It also might not work: the cancer might already have spread, unnoticed, beyond the prostate. Considering these odds, the operation should take place immediately before he strikes the last bull'seye. But that's impossible. By definition, one can never predict when a random event will occur. A more realistic goal is needed. One of the bull'seyes - imagine that it is painted green - corresponds to the genetic change that triggers the propensity to spread that is cancer's most deadly feature. The other five bull'seyes can be hit without any real menace. The problem is that no one can say when a dart has struck the green bull'seye.
To be an ideal diagnostic test, the PSA would be positive only when the player has struck the green bull'seye. Instead it is like an alarm that rings when the player has hit two or more. It does not tell him which two bull'seyes he has hit; and because BPH, too, can increase the level of PSA, he may in fact have hit none at all. Are we better off for having installed this imperfect alarm nationwide? The answer depends on whether its use will lead to what social scientists call increased wellbeing. Everyone I have spoken with has an opinion on the use of the PSA test, favorable or un . But no one says that his or her opinion was empirically established, based on the sort of controlled data that biomedical researchers like. No scientific study has demonstrated that the PSA test saves lives, though it might seem logical to suppose it would. Indeed, none has shown definitively that surgery leaves people better off than doing nothing. As a result, John Wasson says, the United States is rapidly putting the cart before the horse. "We're using at an explosive rate a technology that has not proven itself," he says. "The Europeans at the international meetings I go to are aghast. They say, 'What are you people doing over there?"
A Better Surgical Outcome (Less Impotence)
FROM a surgeon's point of view, the big change in the prostate world began when one of Patrick Walsh's patients experienced no long-term impotence or incontinence after the operation Walsh had performed on him. Walsh was flabbergasted. He had removed the man's prostate, and doctors had known for decades that radical prostatectomy always had these side effects. It was a desperate operation for men in desperate circumstances, because it left most men impotent, incontinent, or both. "I congratulated him, of course," Walsh told me when I visited him recently. "But what I was thinking was, This man cannot be unique. If he could be spared these things, others could."
Then as now Walsh directed the James Buchanan Brady Urological Institute, at Johns Hopkins. Slight, usually softspoken, and possessed of slim, delicate hands, Walsh graduated from the Case Western Reserve University School of Medicine in 1964 and trained as a surgeon for seven years in Boston and Los Angeles before coming to Johns Hopkins. His specialty was urology, the treatment of the reproductive organs in men and the urinary tract in men and women (though most urological patients are men). Urologists work on kidneys, bladders, testicles, and other parts of the body, but they are most often called upon to assist in the treatment of prostate disease. Radical prostatectomy, often the only available treatment for prostate cancer, was a thoroughly unsatisfactory operation. "You were working blind," Walsh told me. "If you thought about it, it would scare you out of your wits." The incision caused so much bleeding from so many sources that the cavity filled faster than suction tubes could drain it. In addition to endangering patients, the blood "prevented you from seeing what on earth you were doing in there." Surgeons had to cut out the prostate by feel.