Improving early cancer diagnosis: it's (mostly) not about screening

In a recent medical news item that you may have missed, an analysis from NORC at the University of Chicago determined that only 14% of cancers in the U.S. are diagnosed by a recommended screening test for breast, cervical, colorectal, or lung cancer.  An additional 11% represent prostate cancers detected through PSA screening, which isn't technically recommended. Adding these two percentages together and subtracting from 100% means that 75% of cancers are either detected incidentally or after patients develop symptoms that cause them to seek medical care. Notably, the study was funded by GRAIL, which sells the Galleri blood test for screening for many types of cancer at once (most without currently recommended tests), and the company no doubt plans to use the results to increase demand for its unproven $949 test. 

However, there is another way to respond to this analysis. If three-quarters of cancers are detected after symptoms develop, the medical community should focus on improving outcomes by reducing the time from symptoms to cancer diagnosis. In a 2022 JAMA Viewpoint and a more detailed paper in Cancer Prevention Research, Dr. Elizabeth Sarma and colleagues made the case for this approach, arguing that symptom detection should be viewed as a "partner to screening" in primary care. People with possible cancer symptoms don't always seek timely care; a mixed-methods systematic review of 80 studies suggested that older adults often initially attribute symptoms to normal aging, but when they do recognize them as potentially serious, they are quicker to see a doctor than younger persons. Another study found that patients with more than two chronic conditions had a longer diagnostic interval (time from primary care presentation to cancer diagnosis) and a higher likelihood of seeking emergency care, possibly because clinicians incorrectly attributed the symptom to the pre-existing condition rather than cancer.

The diagnostic challenge that family physicians face is that most patients with common symptoms that could be due to cancer don't have cancer. If I ordered a CT scan or referred to a gastroenterologist every adult who presented to my office with abdominal pain, many patients would endure a lot of unnecessary procedures to identify the few with colorectal cancer. A 2019 review found few electronic clinical decision support tools for cancer diagnosis in primary care. However, a Veterans Affairs health system study concluded that visiting a primary care clinician at least annually is associated with substantially lower risks of metastatic disease at time of diagnosis and cancer-related death. So what factors influence our decisions to perform tests or refer patients with symptoms that could represent cancer? A systematic review found that the only factors that consistently prompted more diagnostic workups and referrals were alarm symptoms (e.g., fever or unexplained weight loss) and a "gut feeling" that a serious cause was responsible. This isn't good enough. Alarm symptoms are generally obvious, and gut feelings may overestimate or underestimate risk depending on the physician's training and experience.

Although they perform less cancer screening than we do in the U.S., the United Kingdom is well ahead of us in refining systems for early diagnosis. Dr. Sarma observed that U.K. researchers used data from their national heath system to "generate symptom lists and corresponding positive predictive values ... [that] were used to develop interactive calculators for primary care practice to predict an individual's risk of cancer." She endorsed a three-pronged research agenda: describing pre-diagnostic care pathways for symptomatic cancers; identifying signs and symptoms that can be used to identify patients at higher risk for specific cancers; and improving diagnostic pathways for symptomatic patients by increasing patient awareness and improving point-of-care tests in primary care. Can the U.S. successfully emulate the U.K. model of improving early cancer diagnosis?

A "hot take" on screening colonoscopy

Screening for colorectal cancer is an important preventive health practice that saves lives. But is colonoscopy really the "gold standard" for colorectal cancer screening? In Episode 172 of the American Family Physician podcast, I provided my "hot take" on a recent randomized trial that was designed to inform the answer to this question. You can listen to it in the embedded player starting at 22:50 or read the transcript below. Health care professionals may also be interested in a more in-depth discussion that I participated in for Medscape.

Hi, I’m Kenny Lin, deputy editor of AFP and an expert in cancer screening guidelines.

In 2002, the US Preventive Services Task Force first recommended colonoscopy as a primary screening test for colorectal cancer (CRC) in adults. This was an uncharacteristic decision, since the first randomized trial of colonoscopy would not be published for another 20 years.

Since then, flexible sigmoidoscopy has virtually disappeared as a screening option, and colonoscopy has become the primary screening method in the U.S. Gastroenterologists call it the “gold standard” and portray stool-based tests as an inferior alternative to be offered only to patients who refuse.

Of course, colonoscopy is less convenient and has serious risks that stool tests don’t: perforations, bleeding, and infections. The Task Force and others have assumed that colonoscopy saves more lives than stool tests, which reduce CRC mortality by around 15%, or flex sig, which lowers it by 25 to 30%. So the first trial results were surprising, even shocking. After 10 years, the group invited to undergo screening colonoscopies developed fewer cancers, but there was no change in CRC mortality.

Some have argued that a longer follow-up period, higher adherence in the intervention group, and better trained endoscopists might have produced better results. But at a minimum, this landmark trial suggests that it is not accurate to inform patients that colonoscopy is the best test for CRC screening or ethical to recommend it preferentially.

Instead, we should explain that stool-based tests and colonoscopy have different benefits, harms, and screening intervals; that either test is better than none; and then let them decide. On a health system level, it may be worth taking another look at flex sig, an office procedure that older family physicians like me were trained to perform before the promotion of screening colonoscopy got out ahead of the evidence.

My favorite public health and health care books of 2022

My Christmas post is the 7th in an annual series listing my 10 favorite public health and health care reads of the past year. Not all of these were first published in 2022. Happy holidays and warm wishes for a healthy and rewarding New Year!

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1. Empire of Pain: The Secret History of the Sackler Dynasty, by Patrick Radden Keefe

2. The Good Nurse: A True Story of Medicine, Madness, and Murder, by Charles Graeber

3. A Good Time to Be Born: How Science and Public Health Gave Children a Future, by Perri Klass

4. The Price We Pay: What Broke American Health Care - and How to Fix It, by Marty Makary

5. Searching for the Family Doctor: Primary Care on the Brink, by Timothy Hoff

6. Sickening: How Big Pharma Broke American Health Care and How We Can Repair It, by John Abramson

7. A Silent Fire: The Story of Inflammation, Diet, and Disease, by Shilpa Ravella

8. The Song of the Cell: An Exploration of Medicine and the New Human, by Siddhartha Mukherjee

9. White Hot Light: Twenty-Five Years in Emergency Medicine, by Frank Huyler

10. Within Our Grasp: Childhood Malnutrition Worldwide and the Revolution Taking Place to End It, by Sharman Apt Russell

Decoding doctor-speak, redux

Eleven years ago, I wrote a post for my U.S. News Healthcare Headaches blog titled "Decoding doctor-speak: translations of common medical terms" that walked non-health professionals through explanations of common blood tests such as the complete blood count, basic metabolic panel, liver function tests, and low-density lipoprotein; and diagnoses such prediabetes and metabolic syndrome. It turned out to be an enduring hit; the cross-posted version on Common Sense Family Doctor has been viewed more than 11,000 times. But have I or physicians in general have gotten any better at keeping insider medical jargon out of our conversations with patients?

A few weeks ago, JAMA Network Open published a cross-sectional study that assessed the general public's understanding of English phrases that have different meanings in a medical context (jargon) than they do in everyday life. Researchers surveyed 215 adult volunteers without a history of medical or nursing training who visited the 2021 Minnesota State Fair. Of the 13 questions concerning various terms, the percentage of participants who answered correctly ranged from the high 90s ("negative" cancer test results being good news) to 20 or less ("impressive" x-ray results, NPO = nothing by mouth, occult infection).

More people believed that the phrase “had an occult infection” had something to do with a curse than understood that this meant that they had a hidden infection. Fewer than half knew that their neuro examination being “grossly intact” was a good thing, possibly because the word “gross” more often means “unpleasant” than “in general” in common usage. These terms may not necessarily be recognized by clinicians as jargon because they do not land in the commonly understood category of technical, medical terminology. However, they have been shown to be used frequently in clinical settings.

Although I now have more than twice as much clinical experience as I did when I wrote my original blog post, keeping my "doctor-speak" free from jargon remains a work in progress. It's easy to fall into the trap of thinking that patients understand what I'm saying if they are nodding or not asking questions, but as often as that may be true, it could also mean that they are too intimidated or embarrassed to admit that I've lost them. And the burden of assuring that effective communication occurs ought not to fall primarily on the patient. So I resolve to keep trying to do better.

Can prostate MRI reduce the harms of PSA screening?

Without question, PSA screening for prostate cancer in asymptomatic patients does them both harm and good; the difficulty in quantifying how much harm versus good has historically been the source of disagreements among primary care physicians and urologists over how much screening we ought to be doing, or if we should be screening men at all. In 2012, the U.S. Preventive Services Task Force took the position (which it partially reversed in 2018) that the way to prevent harm from PSA screening was to generally stop doing it. But those who believe that selective testing saves lives that otherwise would have been lost to prostate cancer argue that too much testing isn't the problem, it's too much treatment. For every potentially fatal tumor identified by PSA testing, we also "overdiagnose" numerous low-grade, indolent prostate cancers that should perhaps not be called "cancer" at all but are nonetheless treated or at least monitored, exposing patients to harm with very little likelihood of benefit.

It's instructive to compare the typical evaluation for a positive prostate cancer screening test with a positive breast cancer screening test. If breast surgeons diagnosed breast cancer the way urologists diagnose prostate cancer, they would not only biopsy the area of the breast corresponding to an abnormality on a mammogram or ultrasound, they would also systematically biopsy 12 to 20 additional normal-appearing areas of the breast to make sure that no cancer is missed. If that sounds crazy, that's because it is. Multiparametric MRI is increasingly being used for targeted prostate biopsy and active surveillance of low-risk prostate cancer, but whether MRI-targeted biopsy can safely replace systematic prostate biopsy remains an unanswered question.

Unanswered, that is, until last week, when the New England Journal of Medicine published the results of a randomized trial comparing MRI-targeted versus systematic biopsy in men with a PSA level of 3 ng/mL or higher. The researchers found that men in the systematic biopsy group were twice as likely as those in the MRI-targeted group to be diagnosed with an "insignificant" cancer (as judged by pathologists) but slightly less likely to be diagnosed with a clinically significant cancer. In other words, the cost of reducing prostate cancer overdiagnosis is that a small number of clinically significant cancers that would only have been diagnosed with systematic biopsy are missed and not caught until later in the disease course. Granted, pathology does not correlate perfectly with tumor behavior, and it may not predict clinical prognosis since many men have comorbid medical conditions that are more likely to cause death than prostate cancer. But I think these findings make sense; whether and how they will affect academic or community urology practices remains to be seen. As a family physician, would I feel more comfortable with doing PSA screening if I knew that our local urologists performed MRI-targeted rather than systematic prostate biopsies? Absolutely.

New AAFP practice guideline sets blood pressure targets for adults with hypertension

From 1977 to 2003, seven Joint National Committees (JNC), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), produced consensus multi-specialty guidelines on the diagnosis and management of hypertension. In 2013, well into the development of JNC8, the NHLBI abruptly turned the process over to the American College of Cardiology/American Heart Association (ACC/AHA). The JNC8 committee independently published an evidence-based guideline in JAMA that raised the blood pressure treatment threshold in most older adults from 140/90 to 150/90 mm Hg. Concerned about conflicts of interest and other deviations from Institute of Medicine-recommended practices for developing trustworthy guidelines, primary care groups, including the American Academy of Family Physicians (AAFP), declined to participate in the ACC/AHA guideline panel. And the longstanding edifice of hypertension guidelines fractured.

In 2017, the ACC/AHA released its clinical practice guideline, which most notably re-defined hypertension as sustained blood pressure over 130/80 mm Hg and recommending, based largely on the controversial SPRINT trial, that treatment should aim to reduce blood pressure below this new threshold. The AAFP decided against endorsing the guideline and advised its members to continue following the JNC8 report and its own 2017 practice guideline, co-authored with the American College of Physicians, that largely reiterated JNC8’s treatment thresholds for adults aged 60 years and older.

Last month, American Family Physician published an updated AAFP hypertension guideline, written by a panel of family physicians (including me), which focuses on updated evidence for optimal blood pressure targets in adults. Based on a Cochrane systematic review of randomized controlled trials that compared higher and lower blood pressure targets for primary prevention of cardiovascular disease (76% of study participants did not have preexisting CVD), the AAFP strongly recommends treating to a standard blood pressure target of less than 140/90 mm Hg to reduce all-cause and cardiovascular mortality. Since a lower blood pressure target of less than 135/85 mm Hg further reduces the risk of myocardial infarction (number needed to treat = 137 over 3.7 years) but not mortality, the AAFP recommends that clinicians consider treating to this lower target with shared decision-making. Notably, although the lower target did not increase serious adverse events compared to the standard target, it required patients to take one more anti-hypertensive medication on average and increased non-serious adverse events (number needed to harm = 33).

The AAFP guideline also applies to adults with hypertension and existing CVD, as another recent Cochrane review comparing standard to lower blood pressure targets in this population found no differences in total or cardiovascular mortality, conclusions that were unchanged from an earlier version. The AAFP guideline is mostly consistent with guidelines from the International Society of Hypertension that recommend a treatment threshold of 140/90 in office settings and lower thresholds for blood pressures obtained with home monitoring or 24-hour ambulatory monitoring.

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This post first appeared on the AFP Community Blog.