Overdiagnosis

Cancer screening is the effort to detect cancer early, during its pre-clinical phase—the time period that begins with an abnormal cell and ends when the patient notices symptoms from the cancer. It has long been known that some people have cancers with short pre-clinical phases (fast-growing, aggressive cancers), while others have cancers with long pre-clinical phases (slow-growing cancers). And this heterogeneity has an unfortunate implication: namely, screening tends to disproportionately detect slow-growing cancers (because they are accessible to be detected for a long period of time) and disproportionately miss the fast-growing cancers (because they are only accessible to be detected for a short period of time)—the very cancers we would most like to catch. For more information, see Screening (medicine)#Length time bias.

This long-standing model has a hidden assumption: namely, that all cancers inevitably progress. But some pre-clinical cancers will not progress to cause problems for patients. And if screening (or testing for some other reason) detects these cancers, overdiagnosis has occurred.

The figure below depicts the heterogeneity of cancer progression using 4 arrows to represent 4 categories of cancer progression.

Cancer screening is most useful in detecting slowly progressing cancers but can cause overdiagnosis if very slow or non-progressive cancers are detected.

The arrow labeled "Fast" represents a fast-growing cancer, one that quickly leads to symptoms and to death. These are the worst forms of cancer and unfortunately often appear in the interval between screening tests. The arrow labeled "Slow" represents a slow-growing cancer, one that leads to symptoms and death but only after many years. These are the cancers for which screening has arguably the greatest beneficial impact.

The arrow labeled "Very Slow" represents a cancer that never causes problems because it is growing very slowly. If a cancer grows slowly enough, then patients will die of some other cause before the cancer gets big enough to produce symptoms.

The arrow labeled "Non-progressive" represents a cancer that never causes problems because it is not growing at all. In other words, there are cellular abnormalities that meet the pathologic definition of cancer but never grow to cause symptoms—alternatively, they may grow and then regress. Although the concept of non-progressive cancers may seem implausible, basic scientists have begun to uncover biologic mechanisms that halt the progression of cancer.[3][4][5] Some cancers outgrow their blood supply (and are starved), others are recognized by the host's immune system (and are successfully contained), and some are not that aggressive in the first place.

Cancer that grows too slowly to be likely to harm the patient is usually referred to as a benign tumor. Although some types of benign tumor may require intervention, they are often simply monitored for malignant transformation.[6][7]

The phenomenon of overdiagnosis is most widely understood in prostate cancer.[8] A dramatic increase in the number of new cases of prostate cancer was observed following the introduction of the PSA (prostate specific antigen) screening test. Because of the problem of overdiagnosis, most organizations recommend against prostate cancer screening in men with limited life expectancy—generally defined as less than 10 years (see also prostate cancer screening).

Overdiagnosis has been identified in mammographic screening for breast cancer.[9][10] Long-term follow-up of the Malmo randomized trial of mammography found a persistent excess of 115 breast cancers in the screened group 15 years after the trial was completed (a 10% rate of overdiagnosis).[11] In a letter to the editor, authors not associated with the original study of the data from the randomized clinical trial argued that one-quarter of mammographically detected breast cancers represent overdiagnosis.[12] A systematic review of mammography screening programs reported an overdiagnosis rate of around 50%, which is the same of saying that a third of diagnosed cases of breast cancer are overdiagnosed.[13]

Overdiagnosis has also been identified in chest x-ray screening for lung cancer.[14] Long-term follow-up of the Mayo Clinic randomized trial of screening with chest x-rays and sputum cytology found a persistent excess of 46 lung cancer cases in the screened group 13 years after the trial was completed,[15] suggesting that 20–40% of lung cancers detected by conventional x-ray screening represent overdiagnosis. There is considerable evidence that the problem of overdiagnosis is much greater for lung cancer screening using spiral-CT scans.[16]

Overdiagnosis has also been associated with early detection in a variety of other cancers, including neuroblastoma,[17][18] melanoma,[19] and thyroid cancer.[20] In fact, some degree of overdiagnosis in cancer early detection is probably the rule, not the exception.

Issues with overdiagnosis of infectious diseases, such as malaria or typhoid fever, persist in many regions around the world. For example, malaria overdiagnosis is well-documented in African countries.[21][22] and results in over-inflation of actual malaria rates reported at the local and national levels.[23] Health facilities tend to over-diagnose malaria in patients presenting with symptoms such as fever, due to traditional perceptions (for example any fever being equivalent to malaria) and issues related to laboratory testing (see Diagnosis of malaria).[24][25] Therefore, malaria overdiagnosis leads to under-management of other fever-inducing conditions,[22] but also to over-prescription of antimalarial drugs.[26]

Overdiagnosed patients cannot benefit from the detection and treatment of their "cancer" because the cancer was never destined to cause symptoms or death. They can only be harmed. There are three categories of harm associated with overdiagnosis:

1. Physical effects of unnecessary diagnosis and treatment: All medical interventions have side effects. This is particularly true of cancer treatments. Surgery, radiation and chemotherapy all pose varying morbidity and mortality risks.
2. Psychological effects: there is a burden for an individual simply being labeled as "diseased" (e.g. the burden of being labeled a "cancer patient") and an associated increased sense of vulnerability.
3. Economic burden: Not only the associated cost of treatment (from which the patient cannot benefit, because the disease posed no threat), but also—at least, in the current health care system in the United States—a potential increase in the cost of health insurance or even an inability to procure it (e.g. the diagnosis creates a pre-existing condition that affects health insurance). Similar issues may arise with life insurance. Unlike health insurance, life insurance does not fall under the scope of the Affordable Care Act, thus insurers have even more leeway in denying or reducing coverage or inflating premiums due to the patient's condition.

While many identify false positive results as the major downside to cancer screening, there are data to suggest that—when patients are informed about overdiagnosis—they are much more concerned about overdiagnosis than false positive results.[27]

Overdiagnosis is often confused with the term "false positive" test results and with misdiagnosis, but they are three distinct concepts.[28] A false positive test result refers to a test that suggests the presence of disease, but is ultimately proved to be in error (usually by a second, more precise test). Patients with false positive test results may be told that they have a disease and erroneously treated; overdiagnosed patients are told they have disease and generally receive treatment. Misdiagnosed patients do not have the condition at all, or have a totally different condition, but are treated anyway.

Overdiagnosis is also distinct from overtesting. Overtesting is the phenomenon where patients receive a medical test that they don't need; it will not benefit them.[29] For instance, a patient that receives a lumbar spine x-ray when they have low back pain without any sinister signs or symptoms (weight loss, fever, lower limb paresthesia, etc.) and symptoms have been present for less than 4 weeks. Most tests are subject to overtesting, but echocardiograms (ultrasounds of the heart) have been shown to be particularly prone to overtesting.[29] The detection of overtesting is difficult; recently, many population-level estimates have emerged to try to detect potential overtesting. The most common of these estimates is geographical variation in test use. These estimates detect regions, hospitals or general practices that order many more tests, compared to their peers, irrespective of differences in patient demographics between regions.[30][31] Further methods that have been used include identifying general practices that order a higher proportion of tests that return a normal result,[30] and the identification of tests with large temporal increases in their use, without a justifiable reason.[32]

The concept of undiagnosing is a strategy to review diagnostic labels and remove those that are unnecessary or no longer beneficial. It is important that the medical record is updated to reflect the removal of the diagnosis.[33]

• Disease mongering
• False positive
• Medicalization
• Interventionism (medicine)
• Patient education
• Schooliosis
• Screening (medicine)

• Welch, H. Gilbert, Schwartz, Lisa. Overdiagnosed: Making People Sick in the Pursuit of Health. Beacon Press; 2011-01-18. ISBN 9780807022009.