Prostate Screening and the Public’s Health

For the first time in several years, I am writing about prostate cancer screening. I had hoped that this was sufficiently covered in 2009, with PSA Screening: What is the value? (March 21) and the excellent guest piece by Robert Ferrer, PSA Screening: “One of Medicine's Great Success Stories"? (October 27), and finally a bit of celebration in 2011 with PSA redux: The USPSTF finally recommends NOT getting it! (October 14). However, like the proverbial bad penny (or to use a more au courant analogy, zombie), this issue continues to return from the dead. The most recent effort is “Bring Back Prostate Screening”, a NY Times op-ed piece by Deepak A. Kapoor on July 6, 2015.

What Dr. Kapoor is suggesting is obvious from the title, but the question is “is there some new information, some new research, that now makes such screening more reasonable or appropriate?" The answer, unfortunately (because it makes more work for the zombie hunters) is “no”. Dr. Kapoor suggests that there is. He notes research is this field is “... now paying off.” He says that the decision to recommend against prostate screening by the US Preventive Services Task Force “…didn’t take into account adaptations that urologists have made to help better identify patients likely to develop deadly prostate cancers.” He cites the increased sensitivity of PSA screening, the individualization of it to the risks of different men, and the use of PSA trajectory (its rate of increase, or not), as well as new methods of assessing cancer like MRI. However, his assertion is incorrect; all of this information was available to the USPSTF when it made its recommendations, and was taken into account. It is not new.

“At the time,” Dr. Kapoor notes, “I and many other urologists warned of public health repercussions. Our fears have materialized. Since 2010, fewer biopsies have been performed and fewer prostate cancers found. But studies show an increase in the risk that a cancer, when found, will be more aggressive.” This sounds scary, but it is to be expected; when you stop screening everyone you won’t find the cancers early. A big part of recommending against PSA screening was that so many of the cancers it identified were indolent and not going anywhere; the aggressive cancers will be the ones that eventually show up. Indeed, he actually acknowledges that “No increase in cancer mortality has been observed,” but continues to raise the alarm with “…that may be a matter of time; aggressive cancers are less treatable.” So maybe we should be scared.

Well, in fact all prostate cancer is treatable. All cancer is; in fact all conditions are. The question is how effective is the treatment? Does it cure? Does it prolong life? Does it improve the quality of remaining life? This is the area that Dr. Kapoor and his colleagues do not address, because, for prostate cancer, the answer is basically no. If you have the more common kind of prostate cancer, it is slow-growing (indolent) and may even disappear itself; you will die with it, rather than from it. If you have the less-common aggressive form, you may well die from it, and unpleasantly; prostate cancer metastases go to bone and cause a lot of pain. Sadly, however, treatment does not seem to impact this. The “cures” from treatment of prostate cancer are of the ones that would have “cured” themselves, or at least not have manifested with symptoms. The mortality from aggressive deadly cancers is not changed by treatment. This is the critical point that discussions of the sensitivity and specificity of PSA or any other kind of screening often ignores. Not only can they not reliably distinguish between the indolent and aggressive types of cancer well, even if they could and we had a test to reliably tell which one you had, it is only of importance if treatment can make a difference. And in terms of mortality, it doesn’t. What about the other results from treatment? Improved quality of life? Well, here even Dr. Kapoor notes that “cancer treatment can reduce quality of life.” If you consider impotence, urinary incontinence, and the many unpleasant and painful effects of radiation on the rectum to lower quality of life, you betcha.

We can dismiss Dr. Kapoor’s comments by saying he is a urologist, and they make their money treating prostate cancer; can you imagine the impact on their income if we didn’t treat it? But this misses the far bigger issue, which is that we are enamored with – and, more important, spend huge amounts of money on-- high-technology interventions rather than the prosaic, low-tech interventions that have actually been demonstrated to improve the public’s health. Screening for prostate cancer, and overuse and reliance on mammographic screening for breast cancer, are huge industries which (even in breast cancer) have had relatively little impact on mortality. Providing good prenatal care and preventing unwanted pregnancy, ensuring treatment of common diseases like hypertension and diabetes, ensuring that children are not only immunized against infectious disease but are well-fed, well-housed, and well-educated, and free from poisoning by environmental toxins (including bullets) – the basic components of public health and primary care -- may seem less sexy and stimulate our collective psyches less, but they are the things that actually increase population health.

One of the newer fascinations is genomics, the identification of each person’s sequence of DNA. The promise of “precision medicine” is that we will find out who has the risk gene for which disease, and treat it directly and appropriately; treatment for cancer will be based on the genes you have just as treatment for bacterial infections is based on the organism identified by culturing it in a microbiology laboratory. It is so exciting! It is so “sci-fi today”! The American Board of Family Medicine, for example, is planning to create a new self-assessment module (“SAM”, tests that family doctors have to complete one of each year to maintain their Board certification) on genomics. On the other hand, it doesn’t think we need one on contraception, which is too small an area (isn’t it just part of “women’s health”? Oh, do men have a role in contraception also?), unlike genomics, which could affect EVERYTHING!

Except, so far, it hasn’t and there is little evidence to suggest that it will anytime soon. I wrote a blog on the topic on February 1, 2015 (“Precision medicine, trade policy and the cost of drugs: benefiting people or profit for business?) after the appearance of a Times op-ed by Mayo Clinic cancer expert Michael Joyner (“’Moonshot’ medicine will let us down”, January 15, 2015); Dr. Joyner has more recently contributed more comprehensive articles on the topic to JAMA (“Seven questions for personalized medicine[1]) and The Lancet (“Is precision medicine the route to a healthy world?”[2]) in which he makes the important point that most disease is not the result of a single gene, but rather the result of a complex interplay of different genes and the environment. Indeed, the only cancer-specific genes that have been identified so far are the breast cancer genes BRCA1 and BRCA2, and no treatment has emerged; we simply say “get mammograms more often and consider prophylactic mastectomy”.

Spending all this money on precision medicine, on high-tech interventions, expensive drugs and devices is like blowing your house budget on art for the walls before you have built it. Some art is great, some is mediocre, and some is poor, but none will hang well on a jerry-rigged house made poorly of shoddy materials because there was no money left. Some high-tech, expensive interventions are worthwhile but what we really need to increase the population’s health is public health nurses making home visits to pregnant and recently delivered women, and their children; public health nurses or community health workers or even doctors making visits to people’s homes to assess the real risk factors to their health and reasons that they might not be able to comply with treatment plans. We need more primary care, not more interventionalists. But most important, we need to apply what we know works, what we know how to do, to everyone.

That is how we move the needle on population health.

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[1] Joyner MJ, Paneth N, Seven Questions for Personalized Medicine, JAMA. 2015 Jun 22. doi: 10.1001/jama.2015.7725. [Epub ahead of print]

[2] Coote, John H, Joyner, Michael J. Is precision medicine the route to a healthy world?. The Lancet385.9978 (Apr 25, 2015): 1617.

Precision medicine, trade policy and the cost of drugs: benefiting people or profit for business?

In a recent (January 29, 2015) New York Times Op-Ed, Mayo Clinic anesthesiologist Michael Joyner writes that “’Moonshot’ medicine will let us down”. What Dr. Joyner is referring to is what is now most commonly called, particularly in the large academic medical centers that have bought into it in a big way, “precision medicine” or occasionally “personalized medicine”. This is the concept that, by knowing your individual genetics, medicine can devise targeted treatments for diseases (most of the emphasis is on cancer) that will work for you, but maybe not for other people. Maybe the treatment most commonly used for the disease isn’t right for you; this would find it out.

It is a very attractive concept, and one that has clearly gained traction since the first complete sequencing of the human genome in 2003, moving from a science fiction idea to a mainstream investment by many institutions. As Dr. Joyner notes, “President Obama’s new budget is expected to include hundreds of millions of dollars for so-called precision medicine. The initiative, which he introduced last week in his State of the Union address, has bipartisan support and is a bright spot in the otherwise tight funding environment for medical research.” That is the “moonshot” part – hundreds of millions of dollars. When other funding for research is stagnant or being cut. Because it sounds cool, exciting, really like something cutting edge, a step toward the day when disease will no longer bedevil the human race. However, Dr. Joyner adds: “Unfortunately, precision medicine is unlikely to make most of us healthier.” Bummer.

Maybe he is wrong. Maybe the medical centers investing heavily in precision medicine, and the federal government which will fund it (of course, the “investing heavily” is not unrelated to the “hundreds of millions in federal funding) are right. “Star Trek” here we come! But let us look at the evidence that Dr. Joyner presents. He notes that most common diseases that affect people, even those with clear association with families and thus likely genetics, such as Type II diabetes, are not the result of a single or even a few genes that could be targeted if they could be fixed. There are multiple genetic characteristics that impact whether someone has a tendency to get DM2. Moreover, whether it actually occurs is a result of a complex interplay between those genetic risks and actual behaviors such as diet and exercise. He argues that it is obesity, caused by behaviors but certainly abetted by social changes in our lives, jobs, and easily availability of cheap high-calorie food leading to obesity, that has been the major culprit, given that DM2 (and obesity) is an epidemic of the last half-century, therefore not a result of any genetic change. In addition, even when there are genetic factors for differences between people in their response to treatment, it turns out that these do not explain most of the difference (“missing heritability”), such as in response to the anticoagulant warfarin (a so-far failed effort to use precision medicine to choose treatment). Treatment of chronic diseases like cystic fibrosis by genetic intervention has been unsuccessful, and cancer (like microbes) mutates a lot faster than genetically normal cells.

Joyner also raises the very real concern that people’s behaviors will change in ways that work against their health when they learn their genetic risk. Some people will use the information that they are at lower genetic risk to adopt risky behaviors. This has been described in many areas, everything from people with negative cardiac tests continuing to smoke and overeat to men who have had negative HIV tests and circumcision to decrease their risk of spreading HIV increasing their unsafe sex practices. He also notes that the opposite test result, finding yourself to be at greater genetic risk, can also lead to unsafe practices because you figure you’re doomed anyway. In addition, he notes that there are some people (“worriers”), “…who might embark on a course of excessive tests and biopsies ‘just in case.’ In a medical system already marked by the overuse of diagnostic tests and procedures, this could lead to even more wasteful spending.”

The main message here is only in part that “precision medicine” is something whose time has not yet come and may or may not ever come. More important thing is that, despite this, the government is planning to invest hundreds of millions of dollars in it. Most important is that money is not being spent on implementing treatments for conditions that we do know how to treat. People who are poor or uninsured cannot access many already available – and often incredibly expensive – treatments for diseases like cancer (see my piece “Squeezing the needy: a truly flawed financing system for healthcare”, March 2, 2013) or hepatitis C or many neurologic diseases. “Precision medicine” treatments are certainly going to be even more costly. In addition, we do not spend the necessary money to address the social determinants of health--housing and food and warmth and education--that make more of a difference in health than all of health care.

Indeed, we invest large amounts of money, public as well as private, in programs that effectively make our health worse. Sometimes this is in subsidies to major environmental polluters (BP, anyone? How about fracking and the Keystone XL pipeline?), and sometimes it is more direct, when we actually invest government funds in making treatments more expensive and less accessible to people, albeit to the benefit of the drug companies? Noted economist Joseph Stiglitz takes this on in another recent Times Op-Ed, “Don’t trade away our health” (January 30, 2015). He describes how the US Trade Representative, who negotiates trade agreements “supposedly on behalf of the American people”, is in fact consistently working on behalf of big corporations. In the case of the Trans-Pacific Partnership, this will mean increased obstacles to lower-cost generic drugs by making competition more difficult. “Just the availability of generics drives prices down: In generics-friendly India, for example, Gilead Sciences, which makes an effective hepatitis-C drug, recently announced that it would sell the drug for a little more than 1 percent of the $84,000 it charges here.”  This competition should be encouraged; it is the essence of capitalism. But our trade representative is representing big business, not people.

Of course, high drug costs are already a reality. On January 28, 2015, the Times’ Business Section previewed a study coming out in the New England Journal of Medicine from Harvard. “Study finds HIV drugs priced out of reach”. Much of the great advance made against HIV in the last few decades come from effective and more tolerable drug regimens. Atripla, for example, is a once-daily combination of 3 drugs (2 made by Gilead, one by Merck), that is extremely effective. But this study shows that the “flexibility” available to insurers under ACA will mean that folks with worse insurance (usually poorer people) will have to pay $3,000 a year more for Atripla than those with better policies. Again, the poor pay more.

Precision medicine may sound good, and certainly cool, and sexy. It may even benefit some people, if at very high cost, in the future. But right now, today, there are lots of conditions we know how to treat and lots of people who are not getting that treatment because they don’t have the money, are not desirable, have diseases not in the most preferred “product lines”. And we are spending federal money on making some of the drugs that we have that we know are effective less available.

Despite publicity about or funding for precision medicine or any other “new idea”, the fatal flaw is that our health system is not about improving our health, it is about profit. This is intolerable.