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Radiologists and Overdiagnosis
Introduction
Radiologists and Overdiagnosis Saurabh Jha, MD Key Words: Overdiagnosis; overtreatment; radiologists; false positives; gold standard. ªAUR, 2015
O
verdiagnosis is the detection of disease when treatment is likely to be redundant or harmful, and awareness of the condition likely to induce anxiety rather than lead to meaningful empowerment (1). The disease is typically at its earlier stages, inhabiting a milder spectrum of phenotype, and clinically silent. Overdiagnosis is not the same as a false positive diagnosis, although both lead to overmedicalization. Overdiagnosis is bona fide disease, a true positive, whereas a person who tests positive for a condition and is later shown not to have that condition is a false positive. The distinction between false positives and overdiagnosis is important to appreciate to understand why overdiagnosis is controversial. The arbiter of a diagnostic test, that is whether the positive test is a true or false positive, is verification by a truth. The truth is known as the gold standard. Disease can be defined at anatomic pathology which is considered the most indisputable truth. Often disease is defined by imaging, clinical features, and laboratory tests, which comprise criteria established through consensus by an expert panel. The criteria becomes the reference standard for the disease. One accepts that a diagnostic test can yield a false positive, as diagnostic tests are imperfect, and the diagnosis rendered by the test is a provisional assumption. For example, a positive cardiac stress test can either be a true or false positive for obstructive coronary artery disease (CAD). The truthfulness of the positive finding on a stress test can be verified at cardiac catheter angiogram, which is considered the gold standard for CAD (2). However, it is less intuitive that the diagnosis of CAD at catheterization, which defines CAD, can be an overdiagnosis, a false positive of kind. What then arbitrates the gold standard for disease? What arbitrates the arbiter, the speaker of truth? Overdiagnosis is often deduced, after the fact, rather than proven ex ante. Let us take thyroid cancer for which there is very strong evidence of overdiagnosis (3). The incidence of papillary cancer of the thyroid has risen several fold in South Korea because of mass screening. The screen-detected cancers
Acad Radiol 2015; 22:943–944 From the Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Received May 23, 2015; accepted May 25, 2015. Address correspondence to: S.J. e-mail: [email protected]. edu ªAUR, 2015 http://dx.doi.org/10.1016/j.acra.2015.05.002
have been treated by surgery, yet the mortality from thyroid cancer has not reduced. The redundancy of treatment is deduced from the fact that the metric which measures the success of treatment of cancer, mortality rates specific to that cancer, is unmoved. This points to overtreatment which, in turn, points to overdiagnosis. Overdiagnosis of papillary carcinoma of the thyroid in South Korea is incontrovertible at a population level. Despite such high level of evidence, it is difficult to prove with certainty that any particular individual with biopsy-proven papillary cancer will be overdiagnosed. Although most thyroid cancers detected through mass screening will be an overdiagnosis, not all cancers will, as some cancers may turn out not to be as indolent as others. What fuels the debate on overdiagnosis is that a subset of patients benefit from the early diagnosis, but one does not know who they are, before the fact. It is easier counseling a person before screening for thyroid cancer that there is a substantial chance of overdiagnosis and that she might consider foregoing the screening, than it is to ascertain that a biopsy-proven papillary cancer is an overdiagnosis and that she should abstain from treatment. Policy makers, however, ought to be responsive to the warnings of overdiagnosis as they should factor the benefits and harms of screening to the entire population, not to any individual in particular. Treatment of screen-detected thyroid cancer in South Korea is not only redundant but also of net disutility at a population level. This means that overdiagnosis is not value-neutral and a state of indifference but of net harm to society. Imaging is inextricably involved in the problem of overdiagnosis for several reasons. Imaging is often used to define disease, either solely or as part of a diagnostic criteria. This is understandable because not every condition is amenable to diagnosis by tissue analysis. Biopsy of the cardiac muscle for the diagnosis of obstructive CAD, a hemodynamic alteration which is symptomatic and can lead to major adverse cardiovascular events, is both dangerous and futile. The burden of diagnosis of CAD falls on angiography, not anatomic pathology. Some conditions cause histologic changes which can be detected on tissue analysis. However, tissue sampling, such as cardiac biopsy, is still best avoided. This is why the diagnostic criteria for cardiac sarcoid do not mandate cardiac biopsy (4). Conditions such as aortic aneurysms, hypertrophic cardiomyopathy, and noncompaction cardiomyopathy (5) of the heart are defined at imaging, which is to say imaging acts as a surrogate for biopsy. 943
JHA
Overdiagnosis occurs because we wish to catch disease before the patient is symptomatic. Overdiagnosis is a consequence of the anticipatory medicine movement which believes that net suffering to society can be reduced if diseases are caught before they are clinically evident. Whatever the logic and the merits of this thinking, imaging, such as mammograms for the detection of breast cancer, is presently one of the most important tools in the armamentarium of anticipatory medicine. Furthermore, the widespread utilization of imaging in the emergency department and in outpatients has led to the detection of incidental findings, which are a reservoir for overdiagnosis, as these findings are, by definition, unrelated to the patient’s primary complaint. Thus, imaging is both a cause of and a gateway to overdiagnosis. It is not surprising that radiologists, who are physicians tasked with the diagnosis of disease, find themselves implicated in overdiagnosis. What is surprising is the scarcity of an exposition of overdiagnosis in the radiology literature. Indeed, the issue is not only infrequently discussed but also considered controversial (6). This is all the more incredulous as radiologists are experts in diagnosis and know the limitations of a diagnostic test. Radiologists do not question the existence of false positives.
944
Academic Radiology, Vol 22, No 8, August 2015
This issue on overdiagnosis in Academic Radiology attempts to fill a void in radiology. As the guest editor of this issue, I have tried to create a balance and have included different perspectives. I believe balance is important not because the truth is a weighted average of perspectives. However, to acknowledge a controversial entity such as overdiagnosis, the counterpoint must be articulated and heard. The aim of these pieces is not to tell readers how to think. The aim is to tell readers what to think about. It is time radiologists thought about overdiagnosis.
REFERENCES 1. Welch G, Schwartz L, Woloshin S. Overdiagnosed: making people sick in the pursuit of health. Beacon Press, 2011. 2. Gould KL, Lipscomb K, Hamilton GW. Physiological basic for assessing critical coronary stenosis. Am J Cardiology 1974; 33:87–94. 3. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid cancer ‘‘epidemic’’—screening and overdiagnosis. NEJM 2014; 371:1765–1767. 4. Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis and Granulomatous Disorders 2007; 27:89–102. 5. Petersen SE, Selvanayagam JB, Weismann F, et al. Left ventricular noncompaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005; 46:101–105. 6. Gur D, Sumkin JH. Screening for early detection of breast cancer: overdiagnosis versus suboptimal patient management. Radiology 2013; 268(2): 327–328.
Radiologists and Overdiagnosis Saurabh Jha, MD Key Words: Overdiagnosis; overtreatment; radiologists; false positives; gold standard. ªAUR, 2015
O
verdiagnosis is the detection of disease when treatment is likely to be redundant or harmful, and awareness of the condition likely to induce anxiety rather than lead to meaningful empowerment (1). The disease is typically at its earlier stages, inhabiting a milder spectrum of phenotype, and clinically silent. Overdiagnosis is not the same as a false positive diagnosis, although both lead to overmedicalization. Overdiagnosis is bona fide disease, a true positive, whereas a person who tests positive for a condition and is later shown not to have that condition is a false positive. The distinction between false positives and overdiagnosis is important to appreciate to understand why overdiagnosis is controversial. The arbiter of a diagnostic test, that is whether the positive test is a true or false positive, is verification by a truth. The truth is known as the gold standard. Disease can be defined at anatomic pathology which is considered the most indisputable truth. Often disease is defined by imaging, clinical features, and laboratory tests, which comprise criteria established through consensus by an expert panel. The criteria becomes the reference standard for the disease. One accepts that a diagnostic test can yield a false positive, as diagnostic tests are imperfect, and the diagnosis rendered by the test is a provisional assumption. For example, a positive cardiac stress test can either be a true or false positive for obstructive coronary artery disease (CAD). The truthfulness of the positive finding on a stress test can be verified at cardiac catheter angiogram, which is considered the gold standard for CAD (2). However, it is less intuitive that the diagnosis of CAD at catheterization, which defines CAD, can be an overdiagnosis, a false positive of kind. What then arbitrates the gold standard for disease? What arbitrates the arbiter, the speaker of truth? Overdiagnosis is often deduced, after the fact, rather than proven ex ante. Let us take thyroid cancer for which there is very strong evidence of overdiagnosis (3). The incidence of papillary cancer of the thyroid has risen several fold in South Korea because of mass screening. The screen-detected cancers
Acad Radiol 2015; 22:943–944 From the Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Received May 23, 2015; accepted May 25, 2015. Address correspondence to: S.J. e-mail: [email protected]. edu ªAUR, 2015 http://dx.doi.org/10.1016/j.acra.2015.05.002
have been treated by surgery, yet the mortality from thyroid cancer has not reduced. The redundancy of treatment is deduced from the fact that the metric which measures the success of treatment of cancer, mortality rates specific to that cancer, is unmoved. This points to overtreatment which, in turn, points to overdiagnosis. Overdiagnosis of papillary carcinoma of the thyroid in South Korea is incontrovertible at a population level. Despite such high level of evidence, it is difficult to prove with certainty that any particular individual with biopsy-proven papillary cancer will be overdiagnosed. Although most thyroid cancers detected through mass screening will be an overdiagnosis, not all cancers will, as some cancers may turn out not to be as indolent as others. What fuels the debate on overdiagnosis is that a subset of patients benefit from the early diagnosis, but one does not know who they are, before the fact. It is easier counseling a person before screening for thyroid cancer that there is a substantial chance of overdiagnosis and that she might consider foregoing the screening, than it is to ascertain that a biopsy-proven papillary cancer is an overdiagnosis and that she should abstain from treatment. Policy makers, however, ought to be responsive to the warnings of overdiagnosis as they should factor the benefits and harms of screening to the entire population, not to any individual in particular. Treatment of screen-detected thyroid cancer in South Korea is not only redundant but also of net disutility at a population level. This means that overdiagnosis is not value-neutral and a state of indifference but of net harm to society. Imaging is inextricably involved in the problem of overdiagnosis for several reasons. Imaging is often used to define disease, either solely or as part of a diagnostic criteria. This is understandable because not every condition is amenable to diagnosis by tissue analysis. Biopsy of the cardiac muscle for the diagnosis of obstructive CAD, a hemodynamic alteration which is symptomatic and can lead to major adverse cardiovascular events, is both dangerous and futile. The burden of diagnosis of CAD falls on angiography, not anatomic pathology. Some conditions cause histologic changes which can be detected on tissue analysis. However, tissue sampling, such as cardiac biopsy, is still best avoided. This is why the diagnostic criteria for cardiac sarcoid do not mandate cardiac biopsy (4). Conditions such as aortic aneurysms, hypertrophic cardiomyopathy, and noncompaction cardiomyopathy (5) of the heart are defined at imaging, which is to say imaging acts as a surrogate for biopsy. 943
JHA
Overdiagnosis occurs because we wish to catch disease before the patient is symptomatic. Overdiagnosis is a consequence of the anticipatory medicine movement which believes that net suffering to society can be reduced if diseases are caught before they are clinically evident. Whatever the logic and the merits of this thinking, imaging, such as mammograms for the detection of breast cancer, is presently one of the most important tools in the armamentarium of anticipatory medicine. Furthermore, the widespread utilization of imaging in the emergency department and in outpatients has led to the detection of incidental findings, which are a reservoir for overdiagnosis, as these findings are, by definition, unrelated to the patient’s primary complaint. Thus, imaging is both a cause of and a gateway to overdiagnosis. It is not surprising that radiologists, who are physicians tasked with the diagnosis of disease, find themselves implicated in overdiagnosis. What is surprising is the scarcity of an exposition of overdiagnosis in the radiology literature. Indeed, the issue is not only infrequently discussed but also considered controversial (6). This is all the more incredulous as radiologists are experts in diagnosis and know the limitations of a diagnostic test. Radiologists do not question the existence of false positives.
944
Academic Radiology, Vol 22, No 8, August 2015
This issue on overdiagnosis in Academic Radiology attempts to fill a void in radiology. As the guest editor of this issue, I have tried to create a balance and have included different perspectives. I believe balance is important not because the truth is a weighted average of perspectives. However, to acknowledge a controversial entity such as overdiagnosis, the counterpoint must be articulated and heard. The aim of these pieces is not to tell readers how to think. The aim is to tell readers what to think about. It is time radiologists thought about overdiagnosis.
REFERENCES 1. Welch G, Schwartz L, Woloshin S. Overdiagnosed: making people sick in the pursuit of health. Beacon Press, 2011. 2. Gould KL, Lipscomb K, Hamilton GW. Physiological basic for assessing critical coronary stenosis. Am J Cardiology 1974; 33:87–94. 3. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid cancer ‘‘epidemic’’—screening and overdiagnosis. NEJM 2014; 371:1765–1767. 4. Diagnostic standard and guidelines for sarcoidosis. Jpn J Sarcoidosis and Granulomatous Disorders 2007; 27:89–102. 5. Petersen SE, Selvanayagam JB, Weismann F, et al. Left ventricular noncompaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005; 46:101–105. 6. Gur D, Sumkin JH. Screening for early detection of breast cancer: overdiagnosis versus suboptimal patient management. Radiology 2013; 268(2): 327–328.