Overtreatment of prostate cancer in the active surveillance era

Concerns about overdiagnosis of clinically insignificant prostate cancer through prostate specific antigen (PSA) screening motivated the 2018 American Academy of Family Physicians’ (AAFP) recommendation against routine screening for prostate cancer. Explaining the AAFP’s position, Drs. James Stevermer and Kenneth Fink wrote in an AFP editorial:

Few men diagnosed with and treated for prostate cancer will experience a mortality benefit, and an estimated 20% to 50% of those treated will never become symptomatic, even without treatment. This high rate of overdiagnosis from prostate cancer screening exposes many men to harms without any potential benefit.

Active surveillance is a management strategy that is intended to limit overtreatment of localized prostate cancer by monitoring patients with periodic PSA measurements and prostate biopsies to delay or avoid curative therapy (radical prostatectomy or radiation therapy) and its adverse effects. Watchful waiting refers to clinical observation only. A recent analysis of the U.S. Surveillance, Epidemiology, and End-Results (SEER) prostate cancer database found that among men with intermediate-risk prostate cancer (based on pathology and a PSA level lower than 20 ng/mL), active surveillance or watchful waiting increased overall from 5% in 2010 to 12.3% in 2020, with higher percentages of patients with more favorable pathology or lower PSA levels choosing one of these strategies. Of note, men older than 80 years were more than four times as likely to choose observation than men in their 50s (24.9% and 6.1%, respectively).

Another study of patients in the Veterans Affairs health system examined changes in the likelihood of curative therapy in men with prostate cancer and limited longevity. Guidelines recommend against PSA screening or curative treatment for prostate cancer in men with life expectancies of less than 10 years because the benefits take more than a decade to appear, whereas the harms manifest in the short term. Nonetheless, among men with intermediate-risk prostate cancer and life expectancies of less than 10 years, overtreatment rose from 37.6% in 2000 to 59.8% in 2019, with 78% receiving radiation therapy and 22% undergoing surgery.

Radiation therapy may be viewed by patients and physicians as having fewer adverse effects than surgery, but it is hardly benign. A prospective cohort study of nearly 30,000 men who participated in two prostate cancer prevention trials found that compared with untreated participants, men who had radiation therapy were 2.76 times more likely to develop urinary or sexual complications, 2.78 times as likely to develop bladder cancer, and 100 times as likely to develop radiation cystitis and proctitis. It makes no sense to expose patients to these risks who have little opportunity to benefit, two geriatricians wrote in a JAMA Internal Medicine commentary titled “Do Not Wait to Consider Life Expectancy Until After a Prostate Cancer Diagnosis”:

Limited life expectancy increases the likelihood of experiencing harms all along the diagnostic and treatment cascade following screening. Time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited life expectancy distracts from monitoring and treating their symptomatic life-limiting illnesses. Also, limited life expectancy increases the likelihood of complications from most procedures, including radiation therapy.

A previous AFP article that reviewed treatment options for localized prostate cancer, including active surveillance, included the patient-administered Charlson Comorbidity Index and a life expectancy table for U.S. men. A 2019 AFP editorial provided more guidance for estimating and having conversations about life expectancy with older patients.

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This post first appeared on the AFP Community Blog.

In asymptomatic severe aortic stenosis, is earlier intervention better?

Affecting three in 100 adults older than 65 years, aortic stenosis is classified as mild, moderate, and severe based on echocardiographic measurements. The onset of symptoms—dyspnea, volume overload, angina, syncope—is associated with a poor prognosis and is the usual indication for aortic valve replacement. Although valve replacement traditionally required open surgery, transcatheter aortic valve implantation (TAVI) has become increasingly common. A JAMA review article quotes a 2020 American College of Cardiology/American Heart Association guideline as recommending surgical aortic valve replacement (SAVR) for patients younger than 65 years, TAVI for patients 80 years or older, and either procedure in patients 65 to 79 years, depending on operative risk and comorbidities.

A recent editorial in the Journal of the American Heart Association discussed a “paradigm shift” in management of severe aortic stenosis: 69% of Medicare fee-for-service beneficiaries who underwent aortic valve replacement from 2012-2019 had TAVI, with the percentage undergoing SAVR falling from 75% in 2012 to just 10% in 2019. In addition, the overall volume of procedures tripled during this period, suggesting either a dramatic increase in disease severity or more likely, a lower threshold for intervention.

Whether aortic valve replacement in older adults without symptoms of severe aortic stenosis is more beneficial than waiting for symptoms of left ventricular dysfunction to develop is a topic of ongoing research. Two randomized trials published last month shed some light on this question. In a multicenter trial in the United States and Canada, 901 patients older than 65 years (mean age 75.8 years) with asymptomatic severe aortic stenosis were randomized to early TAVI or guideline-recommended clinical surveillance. The primary endpoint was a composite of death, stroke, or unplanned cardiovascular hospitalization. After a median follow-up of 3.8 years, patients assigned to early TAVI had lower mortality (8.4% vs 9.2%), fewer strokes (4.2% vs 6.7%), and fewer unplanned hospitalizations (20.9% vs 41.7%). Of the clinical surveillance group, 87% eventually underwent aortic valve replacement.

A second trial in the United Kingdom and Australia studied 224 patients (mean age 73 years) with asymptomatic severe aortic stenosis and a cardiac MRI showing myocardial fibrosis, which predicts left ventricular decompensation and a poor long-term outcome. Participants were randomized to early aortic valve replacement or conservative management. Although the primary outcome, a composite of all-cause death and unplanned hospitalization related to aortic stenosis, occurred less frequently in the intervention group (18%) than in the control group (23%), this difference was not statistically significant (hazard ratio = 0.79; 95% CI, 0.44-1.43). An accompanying editorial observed that this trial, which fell short of its target enrollment of 356 patients, was underpowered to detect a difference in the outcome. Further, because of scheduling difficulties, 14% of participants in the intervention group had not received valve replacement at 12 months after enrollment. Finally, based on older guidelines that limited TAVI to patients at high operative risk, 75% of the intervention group had SAVR rather than TAVI.

Although the results of these trials can be interpreted as favoring early TAVI in patients with asymptomatic severe aortic stenosis, more studies are needed to ensure that the “paradigm shift” toward early intervention is based on good evidence rather than surgical preference.

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This post first appeared on the AFP Community Blog.

My favorite public health and health care books of 2024

Five moving memoirs and five more outstanding nonfiction titles comprise this year's 10th annual list of my favorite health books, listed alphabetically by title below. For more great reads, feel free to browse my lists from 2023, 2022, 2021, and 2015-2020. Hope this list helps with your holiday shopping!

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1. Crisis Averted: The Hidden Science of Fighting Outbreaks, by Caitlin Rivers

2. The Emergency: A Year of Healing and Heartbreak in a Chicago ER, by Thomas Fisher

3. The Good Doctor: A Father, a Son, and the Evolution of Medical Ethics, by Barron Lerner

4. The Hospital: Life, Death, and Dollars in a Small American Town, by Brian Alexander

5. How Medicine Works and When It Doesn’t: Learning Who to Trust to Get and Stay Healthy, by F. Perry Wilson

6. On Call: A Doctor’s Journey in Public Service, by Anthony Fauci

7. Though the Darkness: Medicine, Missions, and Meeting God in Nepal, by Rebecca Martin

8. Until Proven Safe: The History and Future of Quarantine, by Geoff Manaugh and Nicola Twilley

9. War Doctor: Surgery on the Front Line, by David Nott

10. Within Reason: A Liberal Public Health for an Illiberal Time, by Sandro Galea

RFK Jr. and vaccine politics

Several years ago, during the first Trump administration, I excoriated the then-nominee for Secretary of Health and Human Services, orthopedic surgeon Tom Price, for his poor understanding of cancer screening. (Secretary Price was confirmed by the Senate, but ended up serving for less than 8 months and resigning abruptly after Politico discovered he had spent $1 million in taxpayer dollars flying on private jets and military aircraft.) President-elect Trump has stated that he plans to nominate Robert F. Kennedy, Jr. for Secretary of HHS this time around. I don't know RFK Jr.'s views on cancer screening. News stories have focused on his beliefs about water fluoridation, unpasteurized ("raw") milk, and vaccine safety.

Few HHS Secretaries have actually been medical doctors; Dr. Price was the first M.D. to hold the position in 24 years. The position has typically been filled by former Congresspeople, governors, and professional administrators. The majority of the department's budget funds the Medicare and Medicaid health insurance programs. Smaller portions are distributed to researchers through competitive grant applications. RFK Jr. may want to take fluoride out of the water, ramp up consumption of raw milk, and make vaccines optional for school entry, but fortunately, HHS doesn't have direct jurisdiction over any of these issues. State and local governments decide what vaccines to require. As illustrated in a recent Health Affairs analysis, routine vaccine recommendations from the Centers for Disease Control and Prevention (CDC)'s Advisory Committee on Immunization Practices (ACIP) take anywhere from 9 months to 15 years to be incorporated into state requirements for school entry, and in a few cases (such as human papillomavirus vaccine), have yet to be incorporated at all.

I've written previously about the marked contrast between HPV vaccine's extraordinary effectiveness and its underutilization in the U.S., and it strikes me as nonsensical that parents who don't bat an eye at their infants being vaccinated against hepatitis B (a sexually transmitted infection that causes cirrhosis and liver cancer) are reluctant to protect these children a decade later against a sexually transmitted infection that causes cancer. As vaccine law expert Richard Hughes pointed out in a recent essay, however, vaccine politics frequently defies public health interests. As a member of the Arkansas State Board of Health, he unsuccessfully lobbied for an HPV vaccine requirement:

I approached Governor [Mike] Huckabee’s health adviser and mentioned my interest in promoting the policy’s adoption through the board. The governor’s endorsement, I urged, would demonstrate his commitment to public health as he prepared to make a bid for the presidency. The response was a predictable but polite “no.” For all his championing of public health, the governor was a conservative former Baptist pastor. Many of his strongest supporters would undoubtedly object to the vaccine mandate on moral grounds. Moreover, it could cost him support in the 2008 presidential primaries, where he eventually came in second place to John McCain.

In another important paper, University of Pennsylvania professor Angela Shen warned of "three significant forces in play that jeopardize the continued success of vaccines": the withdrawal of federal support for COVID-19 and other vaccines for uninsured adults; a rising tide of misinformation and disinformation; and a "growing political and partisan divide" around vaccines. During the pandemic, RFK Jr. was identified by researchers as one of the "Disinformation Dozen" - 12 people who originated or amplified 65% of misleading or erroneous anti-vaccine claims on social media platforms. In 2019, his anti-vaccine platform was powerful enough to convince a large portion of the population of Samoa to refuse measles, mumps, and rubella (MMR) vaccines after two children died after receiving MMR vaccines that were accidentally mixed with expired anesthetic rather than the appropriate diluent. As a result, the following year a measles outbreak caused 5,700 cases (3% of the population) and 83 deaths.

A CDC report published yesterday showed that uptake of influenza, COVID-19, and respiratory syncytial virus (RSV) vaccine among adults has been modest as we enter the respiratory virus season (previously known as "flu season"). 35% and 18% of adults have received this year's flu and COVID-19 vaccines, respectively, and 30-40% of eligible adults (age >75 or age 60-74 at increased risk for severe disease) have ever received an RSV vaccine (including last year). COVID-19 vaccine uptake is actually a bit higher than last year, though with less than half of seniors having received it, there are still a lot of vulnerable adults out there.

Side note: Kristen Panthagani, writing in Your Local Epidemiologst, had a fantastic post in September explaining the multiple mistakes in health communication that (mis)led many Americans to expect a "perfect" COVID vaccine. The bottom line: no vaccine confers 100% immunity or is 100% protective for life. The reason we rarely see measles or polio or diphtheria anymore is that 95% or more Americans have been vaccinated and have some immunity, so a chain of transmission has trouble getting established. But if and when that percentage drops, watch out! (See Samoa, 2019.)

It shouldn't surprise any of you that I strongly oppose having RFK Jr. become the next Secretary of HHS. It isn't because he isn't a health professional or doesn't have any experience running an organization of this size (or even the smaller size it might become once the inefficiently two-headed Department of Government Efficiency goes after it). It isn't even because he's a longtime antivaxxer. It's because RFK Jr. has shown time and time again that no amount of scientific evidence will change his deeply rooted, crackpot conspiracy theories about public health. Regardless of the actual influence he might wield in this position, America doesn't need RFK Jr. "going wild on health" when going wild means more cavities for kids, more foodborne illnesses, and more suffering from vaccine-preventable diseases.

Cholesterol screening in children

The appropriateness of screening for hyperlipidemia in children has been debated for years in the medical literature, including the pages of American Family Physician. In 2010, Dr. Robert Gauer wrote an editorial arguing that screening could identify children at risk of developing premature atherosclerotic cardiovascular disease (ASCVD) and allow clinicians to counsel these patients about lifestyle modification and to start statin therapy.

On the other hand, an opposing editorial by former U.S. Preventive Services Task Force (USPSTF) Chair Michael LeFevre noted that “only 40 to 55 percent of children with elevated cholesterol and low-density lipoprotein (LDL) levels will continue to have elevated lipids on follow-up,” reviewed limitations in the evidence base for screening and treatment, and cautioned physicians against “caus[ing] unintended negative consequences in our zeal to prevent far-off disease.”

In 2012, an AFP Journal Club piece analyzed an article contrasting the USPSTF’s call for more research on childhood lipid screening to an American Academy of Pediatrics (AAP)-endorsed guideline, which suggested checking lipid levels in all children around age 10. Dr. Andrea Darby-Stewart and colleagues favored the USPSTF’s “more rigorous, albeit conservative” position over the AAP’s:

There is no evidence that early identification of hyperlipidemia in children changes long-term outcomes. Let’s focus our limited health care resources where they may do some good: encouraging physical activity and maintaining an appropriate body weight.

The 2019 article, Right Care for Children: Top Five Do’s and Don’ts by Dr. Matthew Schefft and colleagues, revisited the controversial topic and listed routine hyperlipidemia screening in children and adolescents as an overused intervention. In a Letter to the Editor, Drs. Cezary Wojcik and Samuel Gidding disagreed and offered another justification for universal lipid screening: to detect familial hypercholesterolemia, an asymptomatic genetic condition that affects 1 out of every 250 children and leads to premature coronary artery disease.

In the September 2024 issue of AFP, the USPSTF reaffirmed its previous statements that the evidence is insufficient to determine the balance of benefits and harms for screening for lipid disorders in asymptomatic persons 20 years or younger. A Putting Prevention into Practice case study applied the USPSTF’s statement to a common clinical scenario. Finally, an editorial by Dr. Brian Reamy proposed selectively screening for familial hypercholesterolemia with a lipid profile "for all family members older than 9 years who have a first-degree relative with a premature ASCVD event or a relative receiving treatment for LDL cholesterol greater than 190 mg per dL."

Currently, cholesterol screening in children is uncommon. A US electronic medical record study of more than 3.2 million children found that among 9 to 11 year olds, only 9% had a previous lipid profile, rising to 13% in the 17- to 21-year-old group. Although prospective cohort studies have found associations between childhood risk factors and adult cardiovascular events, the value of a lipid profile as a risk factor was called into question by a recent analysis of seven cohorts in the United States, Australia, and Finland (n = 11,500). A multivariable model derived from the data used age, sex, blood pressure, body mass index, and smoking status to predict adult cardiovascular events. Adding lipid measurements to the model did not improve risk prediction.

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This post first appeared on the AFP Community Blog.

Legalizing cannabis for medical and recreational use: unintended consequences

Four states voted in yesterday's election on ballot measures to legalize or regulate marijuana (cannabis). As of this morning, it appears that Nebraska will legalize medical cannabis, while Florida, North Dakota, and South Dakota rejected legalizing cannabis for recreational use. A recent study described trends in medical cannabis licensure in 38 states and Washington, DC, from 2020 to 2022. The overall number of enrolled patients increased from 3.1 to 4.1 million, but 13 of the 15 jurisdictions that have legalized recreational use saw decreased enrollment, likely because patients no longer needed a clinician’s authorization to legally purchase cannabis. (In my state of Pennsylvania, where recreational use remains illegal, the prevalence of patients using medical cannabis more than doubled from 236 to 549 per 10,000 people.) Of concern, the percentage of patient-reported qualifying conditions with “substantial or conclusive” evidence supporting benefits of cannabis, as according to the National Academies of Sciences, Engineering, and Medicine, declined from 70% to 54%.

A 2022 Agency for Healthcare Research and Quality review and American Family Physician commentary by Drs. Dean Seehusen and Kaitlin Kehoe concluded that cannabis produced “small to moderate short-term pain relief” in patients with neuropathic pain. Similarly, a review of cannabis and pain management in the current issue of the Journal of the American Board of Family Medicine found low- and moderate-quality evidence that cannabis relieves neuropathic pain or rheumatoid arthritis, fibromyalgia, and other chronic noncancer-related pain. Adverse effects are common, with the most serious and prolonged being cannabinoid hyperemesis syndrome. A previous AFP article presented a suggested approach to distinguishing high-risk use and cannabis use disorder from potentially appropriate medical uses.

In New York, where recreational cannabis became legal in 2021, a New York Times Magazine story examined the problems associated with regulating sales of a substance that, similar to tobacco and alcohol, is highly addictive. Unlicensed shops dispensing cannabis vastly outnumber legal dispensaries because the former’s products can be priced more cheaply and thus cater to customers with cannabis use disorder:

Perhaps marijuana is not as bad as alcohol or cigarettes. But saying it is not as bad misses the point: Marijuana does hurt a substantial portion of its consumers, often quite badly. And there is no reason to think that businesses won’t sell marijuana to those it hurts, if they’re allowed to. What the alcohol and tobacco markets show us, rather, is that addiction and profit don’t mix well. … The goal is to find a balance between the harms of prohibition and those of commercialization.

Although many adults in the United State believe that cannabis use and secondhand smoke exposure is safer than that from tobacco, there is ample evidence of negative effects on short- and long-term outcomes. An FPIN Clinical Inquiry found that legalization of recreational cannabis is associated with an increase in cannabis-related emergency department visits. A recent systematic review and meta-analysis of 63 observational studies (n = 438,329) concluded that cannabis use in those younger than 24 years is associated with lower school grades; lower likelihood of high school graduation, university enrollment, and postsecondary degree attainment; and increased school dropout rates and absenteeism.

Finally, a cross-sectional analysis of data from the 2021-2022 National Survey on Drug Use and Health found that 16% of full-time employed adults used cannabis in the previous month, with 6.5% meeting criteria for cannabis use disorder. A dose-response relationship occurred between increasing frequency of cannabis use and cannabis use disorder severity and increased incidence of missed work for illness, injury, or nonmedical reasons.

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This post first appeared on the AFP Community Blog.