Overdiagnosis of cancer is the detection of asymptomatic cancers, often through screening, which are either not growing or growing so slowly that they would never have caused medical problems for the patient in the course of their life. Some of these detected tumors may even disappear spontaneously without treatment. For that reason, they are a major cause of over treatment, which can include serious harm and toxicity such as surgical deaths, major organ loss or disfigurement, and second radiation or chemotherapy cancers.
Q: What should people know about this?
A: It is important because of the health consequences for the patient. Treatment of overdiagnosed tumors cannot benefit the patient, and yes, on the other hand, it can cause significant damage. People should know that many screening tests can lead to overdiagnoses and that the damages resulting from such overdiagnoses should be weighed against the potential benefits of screening. People should know that not all cancers that are screened need to be treated.
Q: How do the different types of screening methods for cancer detect an overdiagnosis?
A: Ideally, screening should detect only those cancers that would grow if left untreated and for which we already have effective therapies that can change the outcome. However, many screening tests available will lead to an overdiagnosis, and the detection of cancers is the main driver of overdiagnosis. This can happen in two different ways: The test itself detects slow-growing or no-growth cancers, or the test is not specific but leads to the incidental discovery of cancer that does not grow. Examples would be prostate-specific antigen analysis which is specific to the prostate-specific prostate cancer-but, since many men harbor life-threatening prostate cancers, Prostate specific antigen analysis may not specifically indicate that it is only an enlarged prostate, and needle biopsy ordered as follow-up may reveal incidental cancer. Another example is the explorations with computed tomography of the abdomen, which have come to have a wide clinical use; can detect tumors that have nothing to do with the original reason for doing CT scans. So, if someone comes with non-specific abdominal pain, a CT scan may show a small tumor inactive in the kidney; or if you are doing a CT scan of the lung for lung cancer screening can lead to an inactive non-lung cancer in the kidney. Another example is the explorations with computed tomography of the abdomen, which have come to have a wide clinical use; can detect tumors that have nothing to do with the original reason for doing CT scans.
Q: How much of an overdiagnosis?
A: We are realizing that it is more common than we had thought for a long time. The number of overdiagnoses differs depending on the type of tumor, its biology and screening, so that the more sensitive the test, the more inactive cancers it will detect. And if the underlying biology is on average slower to grow, such as prostate cancer compared to pancreatic cancer, it is more likely to be overdiagnosed. Some have used the analogy of birds, bears, and turtles or snails. Birds, which can fly before they can even be tested, represent the most rapidly growing cancers, which are not likely to be detected by screening. These spread so quickly that screenings are of little value. Turtles or snails move so slowly that screening is not even needed because you get the same good result regardless of the use of screening. But screenings are good especially for slower-growing tumors. And then, for the middle ones, for the bears, maybe we can detect them in time and intervene to change the result.
P: How does overdiagnosis differ from a misdiagnosis and false positives?
A: An overdiagnosis is a positive screening test with consequent medical procedures leading to a biopsy based on an agreement among pathologists that the biopsy tissue represents a “cancer”, but a cancer that would never harm the patient. A misdiagnosis occurs when a pathologist makes an incorrect diagnosis and, therefore, other pathologists would not agree that it is cancer in any way. On the other hand, false positives happen when the screening test has a positive result but after a procedure it is found that the patient does not have cancer.
Q: Is cancer the only disease where overdiagnostics are done?
A: Any situation in which more screenings (or awareness programs) occur or changes in the definition of underlying disease can lead to an identification of a spectrum of clinical behavior that is always widening. Another form of overdiagnosis is the creation of new disorders that people did not know before and, in doing so, a condition becomes a disease that is treated by putting a label on it. There are several diseases in which we are expanding the definition that can lead to overtreatment because the disease would not have caused any medical problem. This can be about cardiovascular diseases where we are increasingly labeling calcium in the coronary arteries as “heart disease”; And in diabetes in what is called “pre-diabetes.” That is why it is important to bring together researchers from all these fields and areas of study to talk about what is known about the natural history of diagnosed diseases; Of the factors that cause them; Of its consequences; And, as far as is known, how to mitigate overdiagnosis; And how to advise patients about screenings for a variety of diseases. To that end, we will have the third International Conference for the Prevention of Overdiagnosis this September at the headquarters of the National Institutes of Health, NIH,
Q: What is the Division of Cancer Prevention doing to address this problem?
A: One of the ways to mitigate the detriments of overdiagnosis is to devise more accurate methods of predicting the behavior of cancers detected by screening at a molecular level. That will help us to distinguish cancers detected by screening that are important to give them treatment that should at least be seen before we think about treating them with often toxic therapies. This is an attempt to overcome the already old-fashioned methodology of a century ago simply consisting of taking a tissue biopsy, dyeing it and looking at it under a microscope. It is an attempt to see which tumors, many of which look just like the microscope, will have different behaviors. This requires a broad spectrum of scientific areas of study that includes physicians and other health professionals, epidemiologists and demographers, statisticians, as well as molecular biologists and molecular geneticists. And that’s the exact mix of people who are part of our Early Detection Research Network (EDRN). In addition, we are about to launch a consortium specifically dedicated to the characterization of overdiagnosis at a molecular level and mechanistic studies of the molecular pathways that cause the progression of tumors. This is an issue at the interface of better biological understanding and clinical decision-making and screening, and therefore two divisions of NCI, each presenting those perspectives and specialties.
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