That makes absolute sense. But it’s impossible to wade through the corporate speak and get this nation’s most influential cancer spokesman to take a clear position on the USPSTF recommendation. In an opinion piece for CNN.com in May 2012, Dr. Brawley wrote that “the task force’s methods are notable for their scientific rigor,” and “for two decades, mass PSA-based prostate cancer screening was done in this country without direct clinical evidence showing that it was beneficial to patients.” But he won’t directly say that he agrees with the USPSTF. He writes that he hopes “that this new recommendation will put an end to mass screening.”
But is Dr. Brawley against all screening, which is the USPSTF’s message? Does he agree with the D recommendation that PSA screening is harmful? That much isn’t clear. (I reached out to Dr. Brawley for a comment, but did not hear back.)
As with breast cancer, much of the hue and cry against the recommendation came not just from specialists, but also from men who had survived prostate cancer. They included Representative John Barrow, a Democrat from Georgia, who cosponsored House Resolution 5998, the USPSTF Transparency and Accountability Act of 2012. It would mandate that the USPSTF consult more closely with specialists and is still pending at this writing.
Indeed, the screening controversy has never been far from politics, not in an environment in which “Obamacare” was turned into a four-letter word throughout the endless 2012 election cycle. One of the architects of the Affordable Care Act was Ezekiel Emanuel, MD, brother of Rahm Emanuel, Obama’s former chief of staff. Dr. Emanuel, now the chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania’s Perelman School of Medicine, has campaigned vigorously against what he considers needless medical procedures, and he was cast as one of the chief “death panel” villains.
Many others have politicized the issue. Paul Hsieh, MD, cofounder of Freedom and Individual Rights in Medicine, wrote an opinion piece that ran on Forbes magazine’s Web site on July 5, 2012, under the headline: “Is President Obama’s Prostate Gland More Important Than Yours?” He wrote, accurately, that Obama, upon turning 50, had requested and received a PSA test. Wrote Dr. Hsieh: “When President Obama had his routine physical last year, he enjoyed the freedom to consult with his doctors, weigh the pros and cons of PSA testing, and decide for himself what was in his best medical interest. But under ObamaCare, the President will not allow you that same freedom. Instead, the federal government will decide for you.”
At this writing, Medicare is still covering PSA screening despite its D rating. But it is not unreasonable to conclude that that might change. And it is certainly reasonable to surmise that private insurers will stop paying for screenings that have been bashed by a review board with government ties. Here’s more ammunition justifying not paying: The American Academy of Family Physicians (AAFP) has adopted the panel’s recommendation against screening.
Although all the talk from the Right about “death panels” has a hysterical tone to it, the issue raised by Dr. Hsieh, who is no fan of the president, is legitimate. It also highlights the fact that this controversy, adjudged from a political perspective, is at once predictable and incongruous.
The predictable: Democrats are trying to force-feed government down our throats with recommendations that are de facto mandates, while Republicans are all for individual freedom, a free-flowing discussion between doctor and patient.
The incongruous: Democrats are trying to cut needless costs that are strangling our health care system, while Republicans are insisting upon unnecessary tests that drive up our health care debt.
Oh, what a tangled web that won’t get untangled soon. Researchers continue to come up with drugs (three new ones are sipuleucel-T [Provenge], abiraterone acetate [Zytiga], and cabazitaxel [Jevtana]) that extend the lives of prostate cancer patients. They are all expensive and they all raise the age-old question of whether they are worth the cost of extending life. What is really needed is a test administered in the early stages of prostate cancer that would better predict its course.
Clearly, the civil war will go on. “Outside of urology, there has been support for the USPSTF,” says Sloan-Kettering’s Peter Bach, who is well known in the field of medical research. “I think [the recommendation against screening] is a direction. We have a long history in health care of adopting technologies and using them more broadly than what they were originally designed for.”
But remember that the USPSTF’s target is family practitioners, and they have by no means embraced the recommendation, the position of the AAFP notwithstanding. James Manley, my doctor, says he is squarely against the USPSTF’s decision and will continue to suggest that most of his patients, even those as young as 40, get PSA screening annually. And you must understand how strongly urologists stand against the recommendation. Jerry Blaivas, MD, a celebrated New York City urologist, is not in favor of PSA screening (you’ll find more on his views in Chapter 13), yet he considers the USPSTF meddlesome. “I don’t mind thoughtful panels or even a recommendation,” says Dr. Blaivas. “But I am utterly opposed to a government mandate if that’s what this comes to.”
So where did all of that leave a man who had already gotten a biopsy because of an elevated PSA? Should I have found a time machine and returned to cancel out all my previous PSA readings?
Here’s a better question: Where did the PSA test come from? And another: Does it tell us anything useful?
CHAPTER 6
... In which the author finds out what the inventor of the PSA test has to say
IN THE MARCH 10, 2010, EDITION of the New York Times, an opinion piece written by Richard Ablin, PhD, appeared under the headline “The Great Prostate Mistake.” Dr. Ablin identified himself as the discoverer of PSA, described the test as “hardly more effective than a coin toss,” and concluded, “I never dreamed that my discovery four decades ago would lead to such a profit-driven public health disaster.”
The column drew widespread attention. To state the obvious, those who agreed generally with the USPSTF that prostate testing was overdone and harmful applauded the piece, while those in the urological establishment and elsewhere who favored PSA testing criticized it. The latter group also included many who believed that Dr. Ablin oversold his urological credentials. Certainly the Times did in identifying him as the inventor of the PSA test, something the newspaper later retracted.
Yes, like almost everything else in the prostate cancer world, the identification of the prostate-specific antigen and the origin of the test most often used to measure the amount of PSA in a man’s blood are steeped in controversy. Before delving into that, though, some basics are necessary.
An antigen is a substance that causes the immune system to produce one or more antibodies against it. So the prostate-specific antigen is exactly what its name indicates: an antigen produced by the prostate. That antigen's role is to liquefy semen so the sperm in the ejaculate are able to swim. Under normal conditions PSA is secreted and disposed of through tiny ducts in the prostate, but prostate cancer doesn’t have a working ductal system. As Dr. Walsh explains it, its ducts are "blind, dead-end streets." So rather than drain into the urethra, PSA builds up, leaks out of the prostate, and shows up in the bloodstream, where it can be measured as a marker for cancer.
According to Dr. William Catalona, who has done research into the origins of PSA and the PSA test, the earliest report on the properties of antigens in the prostate was by Iowa urologist Rubin Flocks in 1960. In the mid-1960s, a Japanese forensic scientist, Mitsuwo Hara, partially characterized and reported on a protein similar to PSA. According to Dr. Catalona, Hara called it “gamma-seminoprotein” and suggested its possible value as forensic evidence in rape cases.
Dr. Ablin was next. On the Web site of the Robert Benjamin Ablin Foundation for Cancer Research, which Dr. Ablin founded in memory of his father, who died of metastatic prostate cancer, it is written: “Dr. Richard J. Ablin and his research team discovered antigens of the human prostate, including prostat
e tissue-specific antigen, that later became known as PSA.”
At least a dozen interview subjects told me that this discovery was not significant, and that, at any rate, Dr. Ablin’s work had nothing to do with the development of the PSA test, which was a task separate and distinct from that of antigen isolation. Clearly, I am not the one to judge whether or not his discovery was scientifically significant.
I reached out to Dr. Ablin, who is a professor of pathology at the University of Arizona, but was not granted an interview. “He is currently working on his own book, and I have advised him not to contribute to any other,” said his literary agent from William Morris.
There is no doubt that credit for development of the PSA test belongs elsewhere, to a man and a team working at the Roswell Park Cancer Institute in downtown Buffalo, which once ranked right up there with the MD Anderson Cancer Center in Houston and Memorial Sloan-Kettering Cancer Center in New York City as a leading cancer research facility and teaching hospital. It was at Roswell in the 1970s that a Taiwanese native named T. Ming Chu, PhD, and his team of scientists and researchers created the test that launched a new age in prostate cancer detection and treatment.
Dr. Chu, a gentle, soft-spoken man in his mid-70s, has been retired for several years, though he remains a professor emeritus of cancer pathology and prevention at Roswell. He and his wife live in the Sandhills region of North Carolina but keep a home in Buffalo, which Dr. Chu visits frequently to fly-fish, his main hobby.
As Dr. Ablin was isolating his antigen, Dr. Chu, armed with a PhD in biochemistry from Pennsylvania State University and three years of post-doc study, arrived at Roswell Park. He received what he calls his “marching orders” from Gerald Murphy, MD, a famed urologist and the director at Roswell. “Dr. Murphy told me I could do whatever research I wanted as long as prostate cancer was part of it,” Dr. Chu said.
At one time Dr. Chu also had National Institutes of Health grants to work on pancreatic and breast cancers, but, as long as Dr. Murphy was around, the prostate was not going to be shoved to the bottom of Chu’s to-do list. The goal was clear: “I was to search for prostate cancer–specific or associate antigens,” he says, “then develop a simple blood test.”
Remember that PSA measurement had nothing to do with cancer screening back then; rather, it was a way to measure the volume of cancerous tissue in the prostate, which it does as nanograms of PSA per milliliter of blood. (A nanogram is one-billionth of a gram.)
It took Dr. Chu several years to get his team in place and secure the clinical support of urologists from around the country. There was no eureka moment, he says, it was more of “an accumulation of incremental results,” but on a glorious day in 1979 Chu and his team isolated the antigen. They say it is wholly different from the antigen discovered by Dr. Ablin. Chu’s team needed to do additional work to purify the antigen and, finally, to design the test, which happened in 1980.
Dr. Chu repeatedly emphasized that he did not make the discovery alone. During an interview at Roswell in November of 2012, he fired up his laptop and showed me a list of every researcher, scientist, and postdoc who worked on it with him, some two dozen names altogether.
But he also wants to make it just as clear that it is not Dr. Ablin who deserves credit.
“Dr. Ablin has never published a single peer-reviewed paper on the subject of PSA,” says Dr. Chu. “I think he has some kind of complex.”
The PSA work of Dr. Chu, who holds 11 other patents beside the PSA test, was widely recognized and applauded, and he remains a lofty personage in the urological world. Dr. Chu says that there is precious little difference in the test his team designed more than 30 years ago and the one being used today.
But from the beginning there was professional consternation about PSA test results, mainly because factors other than cancer—BPH and prostatitis (inflammation of the prostate), to name two—can elevate the PSA level. Somewhat sheepishly, the University of Rochester’s Dr. Edward Messing remembers writing an early paper in which “I said we didn’t know what to do with PSA.” Says Dr. Van Arsdalen, my urologist: “Early on, everybody had a lot more hope that PSA would be better at differentiating cancer from noncancer. It’s specific to the prostate, but it’s not specific for prostate cancer.” The best use for PSA when it first came out was as a marker for the recurrence of cancer, which remains a significant part of its employment today.
No one was—or is—more aware of PSA measurement’s imperfection than Dr. Chu. “The biology of prostate cancer is very, very complex,” says Dr. Chu. “It is a quite heterogeneous disease.” He means that it is unpredictable, that the dreaded aggressive 20 percent just can’t be easily characterized, and that a perfect blood test has yet to be designed. The joke in prostate cancer circles, in fact, is that “PSA” stands not for “prostate-specific antigen,” but for “prostate-specific anxiety.”
Over time, urologists learned more about PSA, how to use it, and when to use it, but the real revolution came when it became widely accepted as a screening test, not just as a marker of cancer volume (see the full story about that in the section on Dr. Catalona in Chapter 13). And eventually the PSA test affixed itself to the prostate cancer equation as closely as the mammogram did to breast cancer.
Even as the USPSTF recommends against the PSA test, there are ever more studies on and experiments using PSA, a constant tinkering.
Dr. Steven Kaplan, the NewYork-Presbyterian Hospital/Weill Cornell Medical College urologist, has led experiments that combine treatment with the BPH drugs finasteride (Proscar) or dutasteride (Avodart) with PSA readings over the course of a year in an effort to detect aggressive prostate cancer in men with high PSA levels who have had negative biopsies.
Men are increasingly getting the “free PSA test,” which measures the amount of PSA that is not bound to other proteins in the blood; for reasons unknown, men with cancer have less free PSA than men who are cancer-free. There is also “PSA density” to calculate and consider. That number is arrived at by dividing the PSA reading by the volume of the prostate. The theory behind PSA density is that a man with benign disease would have a PSA density of about 10 percent and no higher than 15 percent of the weight of his prostate.
The “PCA3 test” is for men who have already had a negative biopsy but a question remains as to whether to do a repeat biopsy. One negative is that it involves an “attentive rectal exam,” in which the doctor has to massage prostatic fluid into the urethra. (For pure amusement, that equates to repeatedly stapling your tongue.)
At this writing, the PCA3 test has just been approved by the FDA, as has the Prostate Health Index (PHI), which combines measurements of total PSA, free PSA, and a subcategory of free PSA called pro-PSA.
The search for a more perfect PSA test—or a more perfect replacement for it—will go on. But those discoveries will not be made by Dr. T. Ming Chu, who even hesitates to launch himself into the USPSTF recommendation debate. “I am not a urologist,” he says, “and neither is Dr. Ablin. He is not involved in the screening and management of prostate cancer patients. He is a scientist and he should restrict debate and conversation to the scientific community.”
But Dr. Chu has looked hard at the evidence used in making the USPSTF recommendation from the perspective of a researcher.
“Speaking strictly from a scientific point of view, the US trial that the panel used was mixed and contaminated,” says Dr. Chu. “They based their findings upon a mixed bag of so-called clinical studies. They put oranges and apples together and compared them, so that the result would show no benefit from PSA testing.”
You are welcome to weigh Dr. Chu’s comments against the reality that he developed the PSA test. And you are welcome to note that PSA tests have become the low-hanging fruit of the medical-testing world. But in Dr. Chu I found a scrupulously honest man, one universally respected in his field.
“There is almost nothing perfect in the medical world,” says Dr. Chu. “But I believe that PSA is as good a screening test for
prostate cancer as the mammogram is for breast cancer.”
CHAPTER 7
... In which the author consults with his urologist, visits a radiologist (just in case), decides against treatment, and opens himself up to second-guessing
AND SO IT CAME TIME FOR MY PROSTATE CANCER CONSULT with my urologist and college friend, Keith Van Arsdalen. Keith’s resident entered the room first. He had the report from my biopsy and he sketched out the numbers.
The most basic way of determining the seriousness of prostate cancer is the Gleason score, a grading system that accounts for the differing patterns that prostate tumor cells take in relation to normal cells. My Gleason, the resident told me, was 3 + 3.
A 1 characterizes cells that are nearly normal, while a 5 represents cells that look completely different from normal prostate cells. The more different they are, the more like cancer they are, and consequently the more ominous they are.
The pathologist grades the two most common tumor patterns seen in the pieces removed from the prostate. So, with a 3, I was in the middle on both patterns. The 3 + 3 is the most common finding from a biopsy of this kind. My score is good news in a way, but as I would discover, it also makes the treatment decision particularly gnarly.
The Gleason should not be looked at like the PSA test’s result, i.e., as a number subject to debate. Certainly there have been mistakes in pathology labs, but if your cancer is scored as, say, 5 + 5, it is an almost indisputable fact that you have aggressive prostate disease. It is not BPH and it is not prostatitis.
The Prostate Monologues Page 5
