Screen detection and tumor growth rates. Cancers have different growth rates, which determine their potential to be detected by screening. Tumor A remains microscopic and undetectable by current technology (although more sensitive tests in the future might render it detectable). Tumor B eventually becomes detectable by screening (*), but its growth rate is so slow that it will not cause symptoms during the life of the individual; its detection will result in overdiagnosis. Tumor C is capable of metastasizing, but it grows slowly enough that it can be detected by screening (*); for some, this early detection will result in survival. Tumor D grows very quickly and therefore is usually not detected by screening. This will present as an interval cancer (i.e. detected clinically in the interval between screening examinations) and has a particularly poor prognosis. Note that of the four tumor types, only Tumor C has the potential to benefit from screening. Red dashed lines represent the natural history of a tumor in the absence of detection by screening. (Figure 1 from Gates, 2014).
A new stool DNA test was recently approved by the FDA for colon cancer screening. My first reaction was “Yay! I hope it’s good enough to replace all those unpleasant, expensive screening colonoscopies.” But of course, things are never that simple. I wanted to explain the new test for our readers; but before I could start writing, some other issues in cancer screening barged in and demanded to be included. They exemplify the dilemmas we face with every screening test. We have covered these issues before, but mainly in reference to mammography and prostate (PSA) screening. My article morphed into a CLT sandwich: colon, lung, and thyroid cancer screening.
The current issue of American Family Physician has a great article on cancer screening. It uses lucid graphics to illustrate lead time bias, length time bias, and overdiagnosis bias, as well the effect of varying tumor growth rates on screening success rates, all concepts that have been covered by Dr. Gorski here. Briefly, screening may do more harm than good if:
- It detects cancerous cells that never would have developed into invasive cancers or harmed the patient in any way;
- Early diagnosis and treatment decrease quality of life without reducing death rates; or
- The test falsely indicates cancer in patients who don’t have it or fails to indicate cancer in some who do. (more…)
When I wrote about colonoscopy in 2010, colonoscopy was thought to be the best screening test for colorectal cancer because it could visualize the entire colon and could remove adenomas that were precursors of cancer. But only fecal occult blood testing (FOBT) and sigmoidoscopy had been proven to decrease colorectal cancer incidence and mortality (by 16% and 28%, respectively). Observational evidence suggested that colonoscopy would reduce the incidence and the number of deaths from colorectal cancer, but there were no randomized controlled trials, and the reduction in incidence of cancer after colonoscopy screening seemed to be restricted to left-sided colon cancers, which didn’t make sense.
We still don’t have any randomized controlled trials of colonoscopy, but a 2013 case-control study from Germany compared patients with and without colorectal cancer and found that those who reported having had a colonoscopy were less likely to develop colon cancer for up to 10 years after the procedure. And now two studies published in the New England Journal of Medicine in September 2013 have shed more light on the subject.
I’m going to follow Mark Crislip’s example and recycle my presentation from The Amazing Meeting last week, not because I’m lazy or short on time (although I am both), but because I think the information is worth sharing with a larger audience.
We’ve all had screening tests and we’re all likely to have more of them, but there is a lot of misinformation and misunderstanding about what screening tests can and can’t do. Screening tests are done on populations of asymptomatic people and must be distinguished from diagnostic tests done on individual patients who have symptoms. Some tests are excellent for diagnostic purposes but are not appropriate for screening purposes.
We’re constantly being admonished to get tested for one thing or another. A typical example was a recent Dear Abby column. She got a letter from a woman who had been screened for kidney disease and learned that she had a mild decrease in kidney function. Abby was shocked to learn that 26 million Americans have chronic kidney disease, and she advised her readers to get their kidneys checked. This was terrible advice. It superficially seems like good advice, because if you have something wrong with your kidneys, you’d want to know about it, right? In fact, if there was anything wrong anywhere in your body, you’d want to know about it. By that logic, it might seem advisable to test everyone for everything. But that would be stupid. It would find lots of false positives, it would create anxiety by picking up harmless variants and anomalies that never would have caused problems, it would be expensive, and it would do more harm than good.
Some people would like to manage their own health care without having to depend on a doctor. They consult Google, diagnose themselves, and treat themselves. The Do-It-Yourself trend in lab tests continues apace. Without a doctor’s order, patients can get legitimate and/or questionable lab tests directly from various companies such as Any Lab Test Now and Doctor’s Data (which has sued Stephen Barrett for exposing their fraudulent “urine toxic metals” test on Quackwatch). Now a new company, Talking20, has jumped on the self-testing bandwagon with an innovative product that allows people to prick their finger, put a drop of blood on a card, and mail it in from anywhere in the world. Multiple tests are done on a single drop of blood. Results will be available online within a week or even sooner.
Please note: the following refers to routine physicals and screening tests in healthy, asymptomatic adults. It does not apply to people who have been diagnosed with diseases, who have any kind of symptoms or signs, or who are at particularly high risk of certain specific diseases.
Throughout most of human history, people have consulted doctors (or shamans or other supposed providers of medical care) only when they were sick. Not too long ago, the “if it ain’t broke don’t fix it” mindset changed. It became customary for everyone to have a yearly checkup with a doctor even if they were feeling perfectly well. The doctor would look in your eyes, ears and mouth, listen to your heart and lungs with a stethoscope and poke and prod other parts of your anatomy. He would do several routine tests, perhaps a blood count, urinalysis, EKG, chest-x-ray and TB tine test. There was even an “executive physical” based on the concept that more is better if you can afford it. Perhaps the need for maintenance of cars had an influence: the annual physical was analogous to the 30,000 mile checkup on your vehicle. The assumption was that this process would find and fix any problems and insure that any disease process would be detected at an early stage where earlier treatment would improve final outcomes. It would keep your body running like a well-tuned engine and possibly save your life.
We have gradually come to realize that the routine physical did little or nothing to improve health outcomes and was largely a waste of time and money. Today the emphasis is on identifying factors that can be altered to improve outcomes. We are even seeing articles in the popular press telling the public that no medical group advises annual checkups for healthy adults. If patients see their doctor only when they have symptoms, the doctor can take advantage of those visits to update vaccinations and any indicated screening tests.
The US Preventive Services Task Force (USPSTF) recommends that everyone aged 50-75 be screened for colon cancer with any one of three options: colonoscopy every 10 years, flexible sigmoidoscopy every 5 years, or fecal occult blood testing (FOBT) every year. Conventional colonoscopy is considered the “gold standard” since it allows for direct detection and biopsy of early cancers and removal of precancerous polyps. It involves passing a long colonoscope via the rectum through the full length of the colon and is also known as optical or visual colonoscopy. A newer and less invasive alternative, virtual colonoscopy or CT colonography, is being promoted by some as the test of choice. Others disagree. One area of controversy is that CTs frequently find “incidentalomas” that require further investigation. An article in the journal Radiology highlights this problem, describing “the clinical drama that follows screening or diagnostic tests.” (more…)
Dr. H. Gilbert Welch has written a new book Over-diagnosed: Making People Sick in the Pursuit of Health, with co-authors Lisa Schwartz and Steven Woloshin. It identifies a serious problem, debunks medical misconceptions and contains words of wisdom.
We are healthier, but we are increasingly being told we are sick. We are labeled with diagnoses that may not mean anything to our health. People used to go to the doctor when they were sick, and diagnoses were based on symptoms. Today diagnoses are increasingly made on the basis of detected abnormalities in people who have no symptoms and might never have developed them. Overdiagnosis constitutes one of the biggest problems in modern medicine. Welch explains why and calls for a new paradigm to correct the problem. (more…)
Everybody knows that colonoscopy is the best test to screen for colorectal cancer and that colonoscopies save lives. Everybody may be wrong. Colonoscopy is increasingly viewed as the gold standard for colorectal cancer screening, but its reputation is not based on solid evidence. In reality, it is not yet known for certain whether colonoscopy can help reduce the number of deaths from colorectal cancer. Screening with fecal occult blood testing (FOBT) and flexible sigmoidoscopy are supported by better evidence, but questions remain. It seems our zeal for screening tests has outstripped the evidence.
Statistics show that the life-time risk for an adult American to develop colorectal cancer (CRC) is approximately 6%. Colorectal cancer is the second leading cause of cancer deaths in the United States. In the US there are currently 146,970 new cases and 50,630 deaths each year. Between 1973 and 1995, mortality from CRC declined by 20.5%, and incidence declined by 7.4% in the United States.
The US Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer (CRC) using fecal occult blood testing, sigmoidoscopy, or colonoscopy, in adults, beginning at age 50 years and continuing until age 75 years. (more…)
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. (more…)