I RECENTLY asked a man named Norman Yang if he was chiefly responsible for inventing the test that has transformed the treatment of prostate cancer. Cancer of the prostate gland is astonishingly common. Estimates vary, but a typical assessment is that one out of ten men has the disease in some form by age fifty. In the natural order of things, though, most of those men will never know they have it, because prostate tumors are usually small and symptomless, and because most of the time they grow so slowly that their hosts die for some other reason before the condition causes trouble. The problem is that prostate cancer is so prevalent that the exceptions to the rule represent a lot of people. According to the American Cancer Society, the disease will kill 35,000 men this year -- putting it in the same ballpark as, though a bit behind, breast cancer.
In the past the lack of symptoms which allowed most men with prostate cancer to live undisturbed made timely detection of the bad cases extremely rare. Doctors looked for possible tumors by inserting a rubbergloved finger into a man's rectum and palpating for lumps in his prostate, an undignified and ineffective procedure avoided by patients and physicians alike. The Department of Health and Human Services has estimated that only one out of ten men in the appropriate age group has an annual rectal exam. As a consequence, more than half of all prostate carcinomas were discovered only after they had spread - by which point it was usually too late. Worse, such tumors frequently disperse to the bones, and even in the dark spectrum of untreatable diseases, bone cancer has a particularly grim hue: pain, long and intense, is a primary symptom. Treatments for advanced prostate cancer, which can include removal of the testicles, are not terribly effective.
In the 1970s Norman Yang was one of the scientists who identified prostatespecific antigen (PSA), a substance that the prostate, and only the prostate, releases into the blood. The researchers discovered that mouse antibodies in a test tube can react to the presence of PSA, that this reaction can be used to measure the level of PSA in human blood, and that a man's PSA level is like a thermometer reading: a sudden rise indicates that something is awry. The something is not always cancer - high PSA readings can also be caused by the ordinary swelling of the prostate that comes with old age. But they indicate cancer often enough that they can be regarded as a signal to perform more tests, usually a biopsy (in this case a sample extracted from the suspect area with a needle).
For many in the field the PSA test changed everything. Simple to perform, not hugely expensive, free of embarrassment and discomfort, it seemed to provide doctors with a way to detect prostate trouble early and accurately. If the PSA level jumped, the next step would be a biopsy - a more unpleasant and costly business, but one justified by the potential gravity of the situation. If the biopsy indicated cancer, a surgeon might be called in. The operation, called a radical prostatectomy, removes the prostate and thus the source of the problem. If performed before the carcinoma spreads, surgery is often successful, in that it ends the threat from cancer. But the procedure is dangerous - it may kill up to one out of a hundred patients outright - and fraught with possible side effects, such as impotence and incontinence. Even so, physicians reasoned, quick detection of prostate cancer would save thousands of people from awful deaths every year.
After PSA was identified, a company named Hybritech, in San Diego, jumped into the market with a testing kit. The Food and Drug Administration approved the Hybritech test in 1986, though solely for the purpose of tracking recurrent cancers; only last June did an FDA advisory panel formally recommend that it be used to detect early prostate cancer as well. (FDA approval for this use is expected in the relatively near future.) Doctors moved much faster. Today PSA measurements for older men are part of the furniture of American health care. According to John Wasson, the director of the Center for the Aging at the Dartmouth Medical School, who coheads the federally funded Prostate Patient Outcomes Research Team, in parts of the nation more than half of older men check their PSA annually. Some anxious types examine it monthly, like the balance in their checking account.
From 1988 to 1992 Hybritech sales rose from $74.7 million to $158.4 million, a rise that tapered slightly after the introduction of PSA tests by other firms, including Abbott Laboratories. (Hybritech itself was acquired in 1986 by another drug giant, Eli Lilly.) Statistics from the National Cancer Institute show that the number of prostate cancers detected rose 16 percent from 1989 to 1990; preliminary data indicate that it jumped another 30 percent from 1990 to 1991, the fastest rise in cancer detection ever recorded. Figures from last year are not available, but I have found no one who believes that the increase has stopped. The increase in diagnosis has been accompanied by an increase in treatment. Wasson estimates that the number of operations for prostate cancer in Medicare patients jumped sixfold, from about 2,600 in 1984, before the PSA test, to about 16,000 in 1990, the latest date for which statistics exist. Today, Wasson says, the number is still higher.
Not every scientist has a chance to affect the lives of so many people, and I wanted to ask Norman Yang how he had done it. Yang was hard to find. To his evident annoyance, he had somehow passed through the entrepreneurial 1980s without making a bundle on the discovery. He runs a biotech outfit in Bellevue, Washington, with five employees, including Yang and his wife, Fumei, in a small office building near a strip mall. When I telephoned the first time, I was not sure that he was the right Dr. Yang. Is this, I asked, the man who helped put together the test that is drastically changing the health prospects of the 28 million Americans who are male and more than fifty years old?
“Yes,” he said. “Unfortunately. If I had known what would happen, I would never have done the work.”
I was surprised at his vehemence but not at his sentiment. Even as Hybritech’s sales have risen, the medical establishment has been torn by a debate over whether the concomitant increase in early cancer detection and treatment is a good thing. The PSA test cannot distinguish between a prostate carcinoma that will never disturb its host and one that is ready to invade bone. The fear is that in the next few years tens of thousands of men will undergo needless operations, with an attendant rise in surgically induced impotence, incontinence, and death. For every surgeon who is full of enthusiasm, another medical professional paints the scary picture of a nation full of otherwise healthy retirees in diapers. Indeed, some critics argue that the dispute over prostate cancer is a case study in one of the American medical system's worst shortcomings - its propensity to embrace expensive treatments without considering their longterm social or medical impact.
Just ahead, these critics believe, are tests for Alzheimer's disease and several other types of cancer. All are common conditions with uncertain prospects for cure. Are we to follow the PSA pattern, and sentence the unfortunates who receive bad news to a round of medical intervention that may only increase their misery? Or, as proponents of the PSA test argue, can earlier, better diagnoses be only beneficial?