Many rare book collectors keep an eye out for an original copy of Seduction of the Innocent, a cause célèbre when it was published back in the 1950s by psychiatrist Fredric Wertham. The tome purported to show that the root cause of juvenile delinquency in the U.S. was comic books! Sensationalistic congressional hearings followed in its wake, with concerned parents tuning in to see comic book publishers berated for their “degenerate” magazines. This was the dark, seamy side of the 1950s: fear, witch-hunts, accusations, and public humiliations. The hearings led to the drafting of a code of conduct that the publishers used for decades to self-censor their comics. The net result was a significant decrease in readership for certain comic book genres, even though the data in Seduction of the Innocent contained, according to a later analysis, “manipulated, overstated, compromised, and fabricated evidence.”
The book title and this last phrase came to mind while I was reading Richard Ablin’s new exposé, The Great Prostate Hoax: How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster. Ablin, the researcher who discovered prostate specific antigen (PSA) in 1970, lays out a very convincing case that innocent men, fearing cancer, have been seduced for decades into taking a nearly worthless screening test with virtually no predictive value by a corrupt medical system. As a result, many of them were subjected to needle biopsies (which can result in serious infections) and then radical prostatectomies (surgery to remove the prostate gland). There is significant morbidity associated with these procedures. They leave many men impotent and/or incontinent, and these physical problems are often compounded by a loss of psychological well-being.
So how, exactly, were men led astray by the PSA test? According to Ablin’s tale, they were beguiled by the virtuous image of their primary care physicians as highly competent, all-knowing individuals who wouldn’t suggest a screening test if it really wasn’t a good idea. Many men were given the test without their knowledge as part of a standard blood workup. They didn’t know that the test has an arbitrarily-defined cutoff score and can’t distinguish between the numerous reasons why someone’s PSA levels may be elevated. They bought in to the hype surrounding high tech treatments such as $200 million proton beam therapy machines and $2 million surgical robots, even though there is no evidence that these technologies produce better overall survival outcomes than conventional treatments. They do, however, cost patients and insurers a great deal more.
The question often gets asked: isn’t it worthwhile to screen large numbers of people if it will lead to a few lives saved? Some medical screening tests are widely accepted (e.g., the Pap test for cervical cancer), but others are viewed as having a sufficient number of problems that their use is not universally accepted. These issues are generally tied to the overall financial costs to society as well as health problems affecting individuals that arise from the process of being tested. How many people do you have to screen to find someone who has the disease being sought? What is the morbidity associated with subsequent tests and treatment? How often does the test provide false positives and negatives? In the case of prostate cancer, the vast majority of men will die from other causes before their slow-growing prostate cancer becomes problematic. For most men, “watchful waiting” has now become the most appropriate course of action.
The FDA originally approved the PSA test in 1986 only to monitor PSA levels in men; it was not to be used for the detection of prostate cancer. Political pressure from men’s health advocacy groups and the general idea borrowed from mammography that “early detection saves lives” eventually led to approval of the PSA test for the detection of prostate cancer (following a controversial advisory panel review) in 1993. The company that originally developed the test also advocated for its expanded use. The cutoff level for normal PSA blood levels was originally set at 4 nanograms per milliliter of blood. However, higher levels of PSA are not specific indicators of cancer. As Ablin sums it up, “the ability of the PSA test to identify men with prostate cancer is slightly better than that of flipping a coin.”
So how is it that the test was approved for the detection of cancer? According to Ablin, “big money lubricates the prostate cancer machine.” The urology community strongly supported its adoption because of their desire to profit from the biopsies and prostatectomies that would result from the test. According to Michael Greenspan, a Canadian urologist, “without radical prostatectomies, more than half of all urology practices in the United States would go belly-up.”
Urologists were not the only ones to profit from the approval of the PSA test for diagnosing prostate cancer. TAP Pharmaceuticals developed leuprolide acetate (Lupron), a drug used to treat prostate cancer by suppressing the production of testosterone, which fuels tumor growth. Whistleblower lawsuits alleged in the mid 1990s that TAP’s sales reps gave urologists kickbacks to prescribe Lupron to men simply on the basis of their having elevated PSA levels. TAP was also charged with illegally inflating the wholesale price of the drug, bilking Medicare out of millions of dollars. TAP wound up paying $875 million—at the time, the largest criminal and civil settlement in the pharma industry’s history.
Prostate cancer treatments have helped fuel the explosion of our nation’s health care costs. It turns out that 85 percent of all radical prostatectomies in the U.S. are done using surgical robots, which cost about $2 million apiece. Studies showed that while men having robotic surgery require less blood transfusions and get out of the hospital sooner than with conventional therapy, there was no difference in cancer recurrence rates. However, men who had robotic surgery had a higher incidence of complications (e.g., incontinence and impotence) than men who had conventional surgeries. The FDA approved the da Vinci surgical robot based on data generated by gall bladder removal surgery, not radical prostatectomies, but prostatectomies are where the big money is made.
Who else profits? Proton beam treatment of prostate cancer, in theory, causes less injury to tissues surrounding the tumor than conventional radiation therapy. According to Ablin, however, there is no data to support the idea that proton beam therapy is more effective than conventional radiation at treating prostate cancer, even though it is much more expensive (78 percent more per Medicare patient). The incidence of side effects is equivalent to what is seen with conventional treatments. Furthermore, proton beam therapy centers could not survive without the income from treating prostate cancer patients. They’d go out of business if the reimbursement rate for proton beam therapy were reduced to what is paid for conventional treatments.
Why was Ablin opposed to approval of the PSA test for the detection of prostate cancer? He gives four reasons:
1) PSA measurements cannot diagnose prostate cancer; the enzyme is secreted by normal, benign, and cancerous prostate cells. PSA levels are affected by many factors, including sexual relations, exercise, prostatitis, and benign enlargement of the prostate.
2) There is no specific level of PSA that detects prostate cancer. Though the original number chosen as a cutoff level was arbitrary, this number was later reduced, leading to even more men being treated.
3) The PSA test cannot distinguish between prostate cancer that is slowly growing or very aggressive. The vast majority of men diagnosed with prostate cancer will die of some other cause before their cancer can progress and kill them.
4) Prostate cancer is an age-related disease; men have a 3 percent lifetime risk of dying of this disease. While 30,000 American men die of prostate cancer every year, the vast majority have localized cancers that never metastasize, and these men eventually die of other causes. Biopsies done on men who died of other causes indicate that 45 percent of men aged 50 to 59 have prostate cancer; this number rises to 65 percent for the 60 to 69 age bracket. These data are independent of PSA scores. As a result, many doctors take a watchful approach to treating prostate cancer, with no interventions (usually biopsies). Ablin claims that most of the one million needle biopsies and 100,000 radical prostatectomies performed in the U.S. each year are unnecessary.
So how did the PSA test win approval for the detection of prostate cancer? According to Ablin’s detailed recounting of the FDA Advisory Board meeting, the test won the vote of the advisory panel only with a number of significant conditions attached. However, these provisions were then dropped when the FDA approved the test. At the Advisory Board meeting, Steven Woolf, science advisor for the U.S. Preventative Services Task Force, stated, “the positive predicative value of the PSA screening is only 1.9 percent. That means that at least 50 men with elevated PSA will undergo unnecessary workups for every man with a clinically significant case…It might be worth subjecting this many men to unnecessary treatment if we knew that one man with cancer would benefit from early detection. But this leads to the second problem with PSA screening: lack of proven benefit. There is simply no evidence that early detection of prostate cancer improves the health of patients.”
Two clinical studies published in 2009 in the New England Journal of Medicine assessed the overall usefulness of the PSA screening program. Their conclusion: “PSA-based screening results in small or no reduction in prostate cancer specific mortality.” These results led the U.S. Preventive Services Task Force to recommend in 2011 against routine PSA screening. According to Task Force co-chair Virginia Moyer, “the bottom line is that science tells us there is very little benefit and significant harms associated with mass routing screening.” This recommendation was met by outrage by a number of groups, including the American Urological Association. However, by 2013, the AUA changed its recommendations regarding the use of the PSA test for screening.
I’ve focused here on the PSA test, but the value of other large population screening tests have also been called into question. Examples include genes associated with increased risk of developing breast cancer, the recent approval of a test for human papilloma virus that some worry may displace the standard Pap test in cervical cancer screening, and direct-to-consumer genetic testing. If you’re considering taking a screening test, it’s a good idea to follow the science and an equally sound notion to track the money. How clear-cut are the screening results, and who bears the responsibility for their interpretation? Who stands to profit if a screening test becomes widely adopted? Don’t be seduced by the mythos conveyed by your physician’s white coat. As Otis Brawley, the chief medical officer of the American Cancer Society put it, “We in medicine need to look into our soul and we need to learn the truth. If your income is dependent on you not understanding something, it is very easy not to understand something.” Patients need to recognize that they need to be their own best advocates for their medical care. You shouldn’t automatically suspend the thinking process just because your doctor has told you something, and this involves more than just getting a second opinion. Sometimes you need to ask your physician hard questions, even if it’s not in your nature to do so. The life you save may be your own.
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