It’s easy to think of medical tests as black and white. If the test is positive, you have the disease; if it’s negative, you don’t. Even good clinicians sometimes fall into that trap. Based on the pre-test probability of the disease, a positive test result only increases the probability by a variable amount. An example: if the probability that a patient has a pulmonary embolus (based on symptoms and physical findings) is 10% and you do a D-dimer test, a positive result raises the probability of PE to 17% and a negative result lowers it to 0.2%.

Even something as simple as a throat culture for strep throat can be misleading. It’s possible to have a positive culture because you happen to be an asymptomatic strep carrier, while your current symptoms of fever and sore throat are actually due to a virus. Not to mention all the things that might have gone wrong in the lab: a mix-up of specimens, contamination, inaccurate recording…

Mammography is widely used to screen for breast cancer. Most patients and even some doctors think that if you have a positive mammogram you almost certainly have breast cancer. Not true. A positive result actually means the patient has about a 10% chance of cancer. 9 out of 10 positives are false positives.

But women don’t just get one mammogram. They get them every year or two. After 3 mammograms, 18% of women will have had a false positive. After ten exams, the rate rises to 49.1%. In a study of 2400 women who had an average of 4 mammograms over a 10 year period, the false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. There are also concerns about changes in behavior and psychological wellbeing following false positives.

Until recently, no one had looked at the cumulative incidence of false positives from other cancer screening tests. A new study in the Annals of Family Medicine has done just that.

They took advantage of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to gather their data. In this large controlled trial (over 150,000 subjects), men randomized to screening were offered chest x-rays, flexible sigmoidoscopies, digital rectal examinations and PSA blood tests. Women were offered CA-125 blood tests for cancer antigen, transvaginal sonograms, chest x-rays, and flexible sigmoidoscopies. During the 3-year study period, a total of 14 screening tests were possible for each sex. The subjects didn’t all get every test.By the 4th screening test, the risk of false positives was 37% for men and 26% for women. By the 14th screening test, 60% of men and 49% of women had had false positives. This led to invasive diagnostic procedures in 29% of men and 22% of women. 3% were minimally invasive (like endoscopy), 15.8% were moderately invasive (like biopsy) and 1.6% involved major surgical procedures (like hysterectomy). The rate of invasive procedures varied by screening test: 3% of screened women underwent a major surgical procedure for false-positive findings on a transvaginal sonogram.These numbers do not include non-invasive diagnostic procedures, imaging studies, office visits. They do not address the psychological impact of false positives. And they do not address the cost of further testing.

These data should not be over-interpreted. They don’t represent the average patient undergoing typical cancer screening in the typical clinic. But they do serve as a wake-up call. Screening tests should be chosen to maximize benefit and minimize harm. Organizations like the U.S. Preventive Services Task Force try to do just that; they frequently re-evaluate any new evidence and offer new recommendations. Data like these on cumulative false positive risks will help them make better decisions than they could make based on previously available single-test false positive rates.

“In a post earlier this year, I discussed the pros and cons of PSA screening. Last year, I discussed screening ultrasound exams offered direct to the public to bypass medical judgment). If you do 20 lab tests on a normal person, statistically one will come back false positive just because of the way normal lab results are determined. Figuring out which tests to do on a given patient, either for screening or for diagnosis, is far from straightforward.

This new information doesn’t mean we should abandon cancer screening tests. It does mean we should use them judiciously and be careful not to mislead our patients into thinking they offer more certainty and less risk than they really do.

Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.