Chapter 078. Prevention and Early Detection of Cancer (Part 6)

Cancer Screening Screening is a means of detecting disease early in asymptomatic individuals, with the goal of decreasing morbidity and mortality. While screening can potentially save lives and has been shown to do so in cervical, colon, and probably breast cancer, it is also subject to a number of biases that can suggest a benefit when actually there is none. Biases can even mask net harm. Early detection does not in itself confer benefit. To be of value, screening must detect disease earlier, and treatment of earlier disease must yield a better outcome than treatment at the onset of...
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Chapter 078. Prevention and Early Detection of Cancer (Part 6) Chapter 078. Prevention and Early Detection of Cancer (Part 6) Cancer Screening Screening is a means of detecting disease early in asymptomaticindividuals, with the goal of decreasing morbidity and mortality. While screeningcan potentially save lives and has been shown to do so in cervical, colon, andprobably breast cancer, it is also subject to a number of biases that can suggest abenefit when actually there is none. Biases can even mask net harm. Earlydetection does not in itself confer benefit. To be of value, screening must detectdisease earlier, and treatment of earlier disease must yield a better outcome thantreatment at the onset of symptoms. Cause-specific mortality, rather than survivalafter diagnosis, is the preferred endpoint (see below). Because screening is done on asymptomatic, healthy persons, it shouldoffer substantial likelihood of benefit that outweighs harm. Screening tests andtheir appropriate use should be carefully evaluated before their use is widelyencouraged in screening programs, as a matter of public policy. Screening examinations, tests, or procedures are usually not diagnostic ofcancer but instead indicate that a cancer may be present. The diagnosis is thenmade following a workup that includes a biopsy and pathologic confirmation. A number of genes have been identified that predispose for a disease, andmany more will be identified in the near future. Testing for these genes can definea high-risk population. The ability to predict the development of a particularcancer may some day present therapeutic options as well as ethical dilemmas. Itmay eventually allow for early intervention to prevent a cancer or limit itsseverity. People at high risk may be ideal candidates for chemoprevention andscreening; however, efficacy of these interventions in the high-risk populationshould be investigated. Currently, persons at high risk for a particular cancer canengage in intensive screening. While this course is clinically prudent, it is notknown if it saves lives in these populations. The Accuracy of Screening A screening tests accuracy or ability to discriminate disease is described byfour indices: sensitivity, specificity, positive predictive value, and negativepredictive value (Table 78-2). Sensitivity, also called the true positive rate, is theproportion of persons with the disease testing positive in the screen (i.e., the abilityof the test to detect disease when it is present). Specificity, or 1-false positive rate,is the proportion of persons who do not have the disease and test negative in thescreening test (i.e., the ability of a test to correctly identify that the disease is notpresent). The positive predictive value is the proportion of persons that testpositive who actually have the disease. Similarly, negative predictive value is theproportion testing negative who do not have the disease. The sensitivity andspecificity of a test are relatively independent of the underlying prevalence (orrisk) of the disease in the population screened, but the predictive values dependstrongly on the prevalence of the disease. Table 78-2 Assessment of the Value of a Diagnostic Testa Condition Present Condition Absent Positive test a b Negative test c d a = true positive b = false positive c = false negative d = true negative Sensitivity The proportion of persons with the condition who test positive: a/(a + c) Specificity The proportion of persons without the condition who test negative: d/(b + d) Positive The proportion of persons with a positive testpredictive value (PPV) who have the condition: a/(a + b) Negative The proportion of persons with a negative testpredictive value who do not have the condition: d/(c + d) Prevalence, sensitivity, and specificity determine PPV a For diseases of low prevalence, such as cancer, poor specificity has adramatic adverse effect on PPV such that only a small fraction of positive tests aretrue positives. Screening is most beneficial, efficient, and economical when the targetdisease is common in the population being screened. To be valuable, the screeningtest should have a high specificity; sensitivity need not be very high.