Can Cancer Ever Be Ignored? - NYTimes.com

As chief medical and scientific officer of the American Cancer Society, Otis Webb Brawley — who is also a professor of oncology and epidemiology at Emory University — is the public face of the cancer establishment. He operates in a world of similarly high-achieving, multiple-credentialed, respectable professionals, where insults tend to be delivered, stiletto-style, in scientific language that lay people aren't meant to understand. So it can be more than a little jarring to hear, for example, James Mohler, chairman of the urology department and associate director of the Roswell Park Cancer Institute in Buffalo, say of his friend: "I have known Otis for over 20 years. He doesn't come off as being ignorant or stupid, but when it comes to prostate-cancer screening, he must not be as intelligent as he seems." Or Skip Lockwood, the head of Zero, a prostate-cancer patient advocacy group, charge that Brawley is more concerned about saving men's sex lives than about saving the men themselves.

Brawley has become the target of these attacks because of his blunt and very public skepticism about the routine use of the prostate-specific antigen, or P.S.A., test to screen men for early prostate cancer. "I'm not against prostate-cancer screening," Brawley says. "I'm against lying to men. I'm against exaggerating the evidence to get men to get screened. We should tell people what we know, what we don't know and what we simply believe."

The P.S.A. test, which was approved by the U.S. Food and Drug Administration in 1986, has become an annual ritual for millions of middle-aged men who assume that finding prostate cancer early will prevent death. By 2008, nearly half of men over 50 reported that they were screened in the previous 12 months. Despite the seeming logic of the P.S.A. test, the evidence that it saves lives is far from conclusive, and Brawley is not the only one questioning it. A growing cadre of doctors, epidemiologists, patients and cancer biologists are rethinking its value. And the most recent studies, while not ending the debate, indicate that routine P.S.A. testing appears not to reduce the number of deaths, and if it does, the benefit is exceedingly modest.

Patients and their doctors are now faced with radically polarized views about the logic of routine testing. On one side are physicians like Mohler, who argue that the test can reduce a man's chances of dying of prostate cancer, plain and simple. This side of the debate is passionate, backed by the persuasive conviction of men who have survived prostate cancer and well financed by the multibillion-dollar industry that has grown up around the testing and treatment of the disease.

The other camp makes a less emotionally satisfying argument: on balance, scientific studies do not support the claim that screening healthy men saves lives. Screening, Brawley and others argue, can lead healthy men into a cascade of further testing and treatments that end up injuring or even killing them. As Richard Ablin, who discovered a prostate-specific antigen, put it in an Op-Ed in The New York Times, using the P.S.A. test to screen for cancer has been "a public health disaster."

So what should a man do when his doctor suggests a routine P.S.A. test? The U.S. Preventive Services Task Force, a panel of independent experts that evaluates the latest scientific evidence on preventive tests and treatments, is charged with making recommendations in just such situations. It already recommends against routine screening for men over 75. According to an internal document, in 2009 the task force conducted an in-depth analysis of data and seemed poised to give routine P.S.A. testing a "D" rating — "D" as in don't do it — for any man of any age. But this was around the time that the task force stated that routine mammography for women ages 40 to 50 was not necessary for every woman. That recommendation caused a public uproar, and Ned Calonge, the task-force chairman at the time, sent the P.S.A. recommendation back for review. One year later, in November 2010, just before midterm elections, the task force was again set to review its recommendation when Calonge canceled the meeting. He says that word leaked out that if the November meeting was held, it could jeopardize the task force's financing. Kenneth Lin, the researcher who led the review, quit his job in protest, and now, nearly two years after its initial finding, it remains uncertain when the task force will release its rating for P.S.A. screening.

Cancer screening is a growing field; existing tests are becoming more sensitive, and new tests are constantly developed. We now have CT scanning for lung cancer, and there is also a blood test marketed by Johnson & Johnson known as a "liquid biopsy," which searches for stray cancer cells in the bloodstream. More testing inevitably brings more treatment, because the urge to correct every cellular anomaly, no matter how small or potentially harmless, is practically irresistible. But if there is one lesson from the P.S.A. test, it is that more information and intervention do not always lead to less suffering.

The popularity of the P.S.A. test as the main weapon against prostate cancer is due in large measure to the earnest and passionate advocacy of William Catalona, a urologist from Northwestern University Feinberg School of Medicine. During his residency training at Johns Hopkins Hospital in the mid-1970s, Catalona set up a clinic for late-stage prostate-cancer patients. Back then, the only tool for finding prostate cancer was a digital rectal exam — actually feeling the prostate through the rectal wall. By the time many tumors could be detected, the cancer was already advanced, and removing the prostate surgically did not offer a reliable cure.

Catalona grew close to many of the men he treated, as well as to their families. "Prostate cancer is a terrible death," he said. "They developed bone fractures, they had a lot of pain, they lost weight. They required heavy doses of narcotics."

Catalona wanted to catch these cancers early, when they might be curable. He noticed that men with more advanced cancers at the time of surgery tended to have the highest P.S.A. levels. Could there be a bright line, a "safe" level of P.S.A. that could distinguish healthy men from those with prostate cancer? After reviewing his own patient records, he decided the cutoff level should be 4 nanograms of P.S.A. per milliliter of blood. He followed up with a study of 1,653 patients. The results, published in 1991 in The New England Journal of Medicine, showed that P.S.A. testing could detect prostate cancer several years earlier than a digital rectal exam.

The test quickly gained powerful support: Gerald Murphy, who held the position at the American Cancer Society now held by Brawley, pushed the society to endorse the test. In 1996, Gen. H. Norman Schwarzkopf, a prostate-cancer survivor, appeared on the cover of Time magazine over the statement "There's a simple blood test everyone should know about."

By then, doctors were using the test for routine screening. "P.S.A. testing was so easy," says H. Gilbert Welch, a professor of medicine at the Dartmouth Institute (full disclosure: one author of this article is an instructor at Dartmouth). Doctors were predisposed to use the test for several reasons. First and foremost, there was the perception that early detection could save lives. It was also easy to administer. "It was a blood test," Welch says. "You didn't need equipment. . . . You didn't need to put any scopes up any part of the body. Heck, you didn't even need to ask the patient if he wanted it; you could just check off the box on a list of tests, like cholesterol, when you did a blood draw." Today it's common for doctors to order the P.S.A. test and patients to take it without talking about what it might really mean.

At one time, Otis Brawley, too, assumed that routine screening was the best medical practice. Sitting in his living room in an Atlanta suburb, Brawley recounted his transformation from believer to skeptic. In 1988, after medical school at the University of Chicago, Brawley landed a prestigious fellowship at the National Cancer Institute in Bethesda, Md. There he came under the tutelage of Barnett Kramer, an oncologist and epidemiologist who went on to become the associate director of the institute's early detection and community oncology program. Kramer walked Brawley through a short history of screening, beginning with the Pap smear, which has been an unqualified success, significantly cutting cervical-cancer deaths.

But other cancer screening tests had not worked out so well. For example, researchers at the Mayo Lung Project conducted a study between 1971 and 1983 to determine whether frequent chest X-rays could help reduce deaths from lung cancer. Chest X-rays detected lots of suspicious spots and shadows on the lungs and probably led to some cures of early lung cancers, but the study ultimately found no difference in death rates between the patients who were screened and those who were not. Kramer suggested one probable explanation: diagnosing the spots picked up by X-ray often requires surgery, which carries a small but definite risk. Brawley knew that many spots seen on X-rays are simply old scars or minor abnormalities commonly seen in healthy people. With so many innocent blips detected, complications from lung biopsies and other invasive tests, along with treatment complications, could kill enough patients to negate any benefit from early detection.

Prostate cancer is the second-leading cause of cancer death among men, after lung cancer. In 2009, it was diagnosed in approximately 192,000 men. A small number of tumors are very aggressive, but the majority of prostate tumors are not likely to cause death. They grow very slowly, and only a fraction break out of the prostate, seed new tumors in other parts of the body and kill the patient. The current thinking is that about 30 percent of men in their 40s have prostate cancer, 40 percent of men in their 50s and so on, right up to 70 percent of men in their 80s. Yet only 3 percent of all men die from the disease. In other words, far more men die with prostate cancer thanfrom it, and only a tiny fraction of prostate cancers ever cause symptoms, much less death.

But here is the tricky part: Unless there are symptoms or a finding on a physical exam, doctors generally cannot accurately predict which cancers are destined to be indolent, to sit around for years growing slowly, if at all, and those that will ultimately prove lethal.

In his discussions with Kramer, Brawley saw that these two pieces of information — the fact that a certain number of prostate cancers will never cause harm, and that doctors can't reliably predict which cancers will be dangerous — had powerful and potentially devastating consequences for men. The first implication was that using the P.S.A. test to screen men who had no symptoms would uncover a huge reservoir of indolent cancers. Most of those cancers that men previously died with — and not from — would now theoretically be detectable. And once detected, the majority of those cancers would be treated.

The most frequent treatment then, as it is now, was the surgical removal of the entire prostate gland. The prostate sits at the base of the penis, wrapped around the urethra, which is the tube that carries urine and semen out of the penis. Trying to separate gland from urethra is a difficult job, and even the best of surgeons can damage the urethra or the bundle of nerves that initiate erections. About half of men who undergo radiation or surgery will have permanent side effects like impotence and incontinence. Up to 1 in 200 men die within 30 days from complications related to the surgery.

"You didn't have to be brilliant to see that history was repeating itself," Brawley says. "Doctors were just substituting a blood test for chest X-rays."

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