Saturday, June 22, 2019

Fear-mongering in thyroid and breast cancer screening

A large part of practicing primary care consists of providing reassurance to healthy persons. The patient who asks me to look at the mole on her back to make sure it isn't melanoma. The patient who recently recovered from a cold but is still coughing and wants to know that it isn't a sign of something more serious. The patient whose friend's doctor found a lump on his thyroid gland and wants to have his neck checked too.

The last time the U.S. Preventive Services Task Force recommended against screening for thyroid cancer was in 1996. That it took more than 20 years to release an updated recommendation statement (still a "D," or don't do) speaks to how non-controversial the Task Force judged this topic to be. Unfortunately, in the interim many clinicians and patients ignored this advice. In South Korea, a national cancer screening program that began in 1999 encouraged general practitioners to routinely perform thyroid ultrasound scans, resulting in an "epidemic" of new thyroid cancers but no change in thyroid cancer deaths. In the United States, papillary thyroid cancer diagnoses have quadrupled since 1995, again with no change in mortality. In both countries and around the world, physicians are finding and treating thousands of pseudo-cancers that would not have otherwise been found and don't need to be treated. Overdiagnosis begets more overdiagnosis: patients who are "successfully" diagnosed and treated tell friends and relatives to have their necks palpated or scanned for thyroid tumors. And if that feedback cycle wasn't enough, advocacy groups such as the Light of Life Foundation initiated fear-mongering awareness campaigns, as Dr. Gilbert Welch described in an editorial accompanying the USPSTF recommendation:

About a decade ago, public service announcements began to appear encouraging people to have their physicians “check your neck.” The Light of Life Foundation campaign featured actual testimonials of patients describing their positive health behaviors on the day before they were diagnosed with thyroid cancer. The ads used compelling language: “Thyroid cancer doesn’t care how healthy you are. It can happen to anyone. Including you. That’s why it is the fastest growing cancer in the US. Ask your doctor to check your neck. It could save your life.” The campaign’s title—and its main slogan—was “Confidence Kills.” That’s a great public health message: if you feel good, you are about to die.

Fear-mongering isn't limited to thyroid cancer, of course. From the 1980s-era American Cancer Society print advertisement that lectured women, "If you haven't had a mammogram, you need more than your breasts examined," promoters of breast cancer screening long used fear to motivate women to undergo screening mammography. In 2015, several advocacy organizations successfully persuaded the U.S. Congress to override the U.S. Preventive Services Task Force's "C" grade (small net benefit) on screening mammography for women aged 40-49 with a "Stop the Guidelines" campaign that included full-page advertisements in major newspapers asking the rhetorical question "Which of our wives, mothers, daughters, and sisters would be be OK to lose?"

The major difference between screening for thyroid and breast cancer is that the latter actually reduces cancer deaths. But women under 50 are less likely to benefit because there is less lethal breast cancer to be found in younger women, and consequently much higher false positive rates that affect more than half of all women receiving annual mammograms from age 40 to 50. And the USPSTF didn't tell clinicians don't screen - more accurately, they said don't screen reflexively, and the message to younger women is not to avoid mammograms, but to talk about the pros and cons with your doctor.

That hasn't stopped a new alliance of radiologists and breast cancer surgeons from targeting the Task Force with a 40not50 campaign which encourages women in their 40s to turn off their brains, eschew shared decision-making, and demand that their doctors start screening them at age 40 because mammograms save lives, and a government-appointed panel (whose 16 current members include 6 women) wants to prevent women from seeing their 50th birthdays. Notwithstanding the ulterior motives behind this absurd campaign, it is insulting to women. It says that they can't be trusted to consider the medical evidence, have conversations with their primary care physicians, and make decisions about their healthcare that are right for them.


This post first appeared on Common Sense Family Doctor on May 16, 2017.

Monday, June 17, 2019

For most, an aspirin a day won't keep the doctor away

A daily low-dose (81 mg) aspirin was once considered an essential component of cardiovascular disease (CVD) prevention for middle-aged and older adults. In 2006, the National Commission on Prevention Priorities ranked "discussing aspirin use in high-risk adults" the highest priority preventive service based on clinically preventable burden and cost effectiveness, and two years ago, in an updated set of rankings, it still rated aspirin use as the fifth highest priority for improving utilization. However, in 2018 the results of three large randomized trials suggested that the harms of aspirin taken to prevent a first CVD event outweigh its benefits for most persons. In an editorial in the June 1 issue of American Family Physician, Dr. Jennifer Middleton and I reviewed the latest evidence and concluded:

The new data do not exclude the possibility that aspirin may still benefit adults at very high CVD risk (e.g., 20% or more over 10 years) or those at lower risk who are unable to tolerate statins, but the data otherwise suggest that the risks of low-dose aspirin therapy for primary prevention outweigh any potential benefits. For most patients, we should be deprescribing aspirin for primary prevention of CVD. To prevent heart attacks and strokes, family physicians should focus instead on smoking cessation and lifestyle changes, controlling high blood pressure, and prescribing statins when indicated.

In a 2019 clinical practice guideline, the American College of Cardiology / American Heart Association largely concurred, recommending against prescribing aspirin for primary prevention of CVD in adults older than age 70 and downgrading its role in other adults at high risk to "may be considered" on a case-by-case basis.

Although aspirin is still strongly recommended to prevent recurrent CVD events, its rise and fall in primary prevention seems to have become another case of medicine reversing itself. Unlike other notable examples of medical reversal such as menopausal hormone therapy and tight glucose control in type 2 diabetes, the effectiveness of aspirin was supported by many well-conducted randomized, controlled trials. Aspirin worked ... until it didn't. In a recent commentary in the Journal of General Internal Medicine, Palmer Greene and colleagues suggested that it may be a good idea to consider established evidence-based practices as having an "expiration date":

An “evidentiary statute of limitations” would require the occasional reassessment of accepted therapies to consider which might no longer be of use—possibly because of changes in the population as a whole, a changing understanding of whom the treatment is appropriate for, or evolving therapies for the prevention or treatment of the disease in question. Not only should we consider if older data still applies, we should also strive to anticipate the factors to which the results of a newly published positive study might be sensitive. For instance, is there an event rate in the control group below which the harms of the therapy might outweigh the benefit? Is there a treatment success rate that, when achieved, would make screening inefficient?

Not starting aspirin is relatively straightforward, but patients who have taken aspirin for many years without adverse effects or CVD events may resist discontinuing it. After making sure that we are appropriately treating all of their risk factors (e.g., high blood pressure, high cholesterol, diabetes, tobacco use), I have taken a shared decision-making approach to these deprescribing discussions, emphasizing the small additional benefit of aspirin compared to the increased risk of serious bleeding events.


This post first appeared on the AFP Community Blog.

Monday, June 10, 2019

The problems with using population-level data to estimate prostate screening benefits

Almost any debate about the effectiveness (or lack thereof) of PSA-based screening for prostate cancer in the U.S. will usually involve whether the results of the two largest randomized screening trials or national mortality statistics more accurately represent the effects of intensive screening from the early 1990s to the late 2000s. Putting aside the conflicting results of the U.S. Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC) - for which there are many plausible explanations - even the most optimistic statistical interpretation of these trials suggests that PSA screening reduces prostate cancer mortality by 25-30% at best, which does not fully account for the observed 40% decline in prostate cancer mortality from 1991 to 2008. Since the effectiveness of standard prostate cancer therapy did not change significantly during this time frame, PSA screening advocates have suggested that the discrepancy is probably due to flaws in the trials, rather than issues with "real-world evidence" derived from population-level mortality data.

However, in a thoughtful commentary recently published in Mayo Clinic Proceedings, Drs. Joaquin Chapa, Alyson Haslam  and Vinay Prasad provide lots of good reasons to question the validity of prostate cancer mortality trends. First, as any clinician who has filled out a death certificate knows, determining the underlying cause of death can be difficult in a patient with several serious health conditions. Patients with metastatic prostate cancer may die with incurable cancer, but not of it. Then, the algorithm used by the Mortality Medical Data System may introduce error, noise, and bias because prostate cancer is accepted as an underlying cause of death for many conditions (e.g., cirrhosis, bacterial endocarditis) that could be related to the cancer but could also simply co-exist.

In addition, studies show that patterns in attribution of causes of death often change over time due to factors other than actual changes in underlying causes. Changes in population composition (e.g., increases in the Hispanic and Asian proportion of the population relative to whites and African Americans) can also result in different overall prostate cancer mortality rates by increasing the percentages of populations who have lower cancer mortality.

In contrast, the methods used to determine causes of death in PLCO and ERSPC were much more rigorous; the cause listed on the death certificate was double-checked by 1 to 3 independent, blinded reviewers. These processes demonstrated that assigning a cause of death is potentially fraught with error and subject to human bias. As Chapa and colleagues observe:

Even with more rigorous processes for determining COD in the PLCO and ERSPC trials, COD determination remains difficult and is subject to uncertainty. Of all deaths in the PLCO study, 28% required additional human review because of discordance between the death certificate and the initial human reviewer. Of reviewed cases, 3% required a conference call to resolve discordance among 3 reviewers.

I've always thought that crediting PSA screening for the historical decline in U.S. prostate cancer mortality made little sense; for one thing, one wouldn't expect a mortality difference to be visible for at least 7-8 years after screening became common in clinical practice, the earliest point in the ERSPC trial when the survival curves separate. That would have been 1997 or 1998 at the earliest, not 1991. Other studies have observed that prostate cancer mortality also began falling in the U.K. in the 1990s, even though PSA screening was uncommon. This new analysis provides even more reason to doubt that there is a straightforward cause-and-effect relationship - if, indeed, there is any relationship at all.

By the way, I'd like to give a shout-out to the terrific medical podcast Plenary Session, hosted by Dr. Prasad. An interview with Dr. Chapa in a recent episode was the reason I knew about his paper in the first place. Plenary Session is too new to have made my most recent list of favorite podcasts, but you can bet that it will be on the next one.