Tuesday, October 19, 2021

The past, present and future of cancer screening

I've given a lecture in Georgetown University School of Medicine's Evidence-Based Medicine course on evaluating screening tests every fall for the past decade, and for several years prior to that I taught these principles to public health students at Johns Hopkins University. I link the origin of evidence-based assessment of clinical preventive services to the creation of the U.S. Preventive Services Task Force (USPSTF) in 1984, first under the aegis of the U.S. Public Health Service and later, the Agency for Healthcare Research and Quality. In doing so, I imply that prior to that date, screening in primary care was in the stone ages. As it turns out, that's not exactly true.

The recent digitization of archives of The Journal of Family Practice dating back to 1974 allowed me to discover a 4-part series of previously inaccessible papers by Drs. Paul Frame and Stephen Carlson titled "A Critical Review of Periodic Health Screening Using Specific Screening Criteria." These historical articles, published before I was born, analyzed screening tests for 36 selected diseases using criteria that would be familiar to anyone studying screening today:

1. The disease must have a significant effect on quality or quantity of life.

2. Acceptable methods of treatment must be available.

3. The disease must have an asymptomatic period during which detection and treatment significantly reduce morbidity and/or mortality.

4. Treatment in the asymptomatic phase must yield a therapeutic result superior to that obtained by delaying treatment until symptoms appear.

5. Tests must be available at reasonable cost to detect the condition in the asymptomatic period.

6. The incidence of the condition must be sufficient to justify the cost of screening.

Here are some of their recommendations for screening in adults that remain essentially unchanged half a century later: Take a smoking history. Measure height and weight. Check blood pressure every 2 years. Don't routinely do EKGs in asymptomatic people. Measure cholesterol levels. Don't screen for lung cancer with chest x-ray or sputum cytology (these days we screen high-risk persons with CT). Don't screen for brain tumors. Don't screen for COPD. Don't screen for cirrhosis (advanced liver disease). Don't screen for oral cancer, stomach cancer, or pancreatic cancer. Perform fecal occult blood testing to screen for colorectal cancer (this remains an option although many patients now choose screening colonoscopy). Don't screen for bacteriuria in nonpregnant patients. Screen for syphilis in at-risk persons. Don't screen for testicular cancer, bladder cancer, or kidney cancer. Do Pap smears for cervical cancer in women older than age 20 (today we may add or substitute HPV testing in certain patients). Don't screen for endometrial or ovarian cancer.

In terms of screening for cancer, there were only two substantial changes from these 1975 guidelines to today's accepted practices. For breast cancer, we now recommend biennial mammography for all women starting at age 50 (or age 40 if desired) and discourage routine breast self-examination, which Frame and Carlson endorsed due to it being a benign intervention - it hadn't yet been shown to be harmful in terms of increasing false positive results and biopsies. And while Frame and Carlson discouraged prostate cancer screening, the current USPSTF thinks that selective screening is acceptable in men age 55-69 years (although I disagree).

The fact is, though, most cancers aren't diagnosable or diagnosed through screening. A a recent National Academies workshop, Dr. Chyke Doubeni noted that less than half of all cancer deaths are potentially preventable through current screening techniques. Dr. Elizabeth Sarma's research showed that only one-third of estimated new cancer cases this year are potentially screen detectable. For example, data show that 67 to 82 percent of colorectal cancers are detected after patients present with symptoms, not due to an abnormal screening test result. This imbalance would improve a little if 100% of eligible adults got screened, but the fact is that current technology can't prevent every cancer, or even the majority of them.

That's a quick tour of the past and present. What about the future of cancer screening? There is a lot of optimism these days about multicancer early detection (MCED) tests, also called "liquid biopsies." Imagine this: your doctor would be able to take a single blood sample and test it for multiple cancers simultaneously, including cancers that currently have no effective standard screening test. That sounds great, but there are lots of potential pitfalls, including the inability of some tests to identify cancer tissue of origin (so you could get a result back that essentially says "You have cancer somewhere in your body, we just don't know where"). Lots of smart people, including yours truly, are trying to figure out the best way to evaluate the benefits and harms of MCED tests and to create regulatory frameworks for the companies that are developing them.