Screening for cancer

Screening is the application of a test to an asymptomatic target population in which a positive result correlates with disease. The measure itself is not diagnostic, and the presence of disease must be confirmed by further diagnostic tests. The goal of screening is to identify disease early in its course, and offer therapy when it can be more effective and associated with lower morbidity.6 The World Health Organization has established criteria for widespread application of a screening programme.6 First, the disease must be a significant health risk in the target population. Second, the screening test must be safe, straightforward to apply and interpret, and meet minimum standards for sensitivity, specificity and predictive values. Third, large-scale application of the measure must be logistically and economically feasible. Fourth, effective therapeutic interventions should be readily available to the screened population. It is crucial to remember, however, that a successful screening protocol demonstrates prolonged survival and decreased disease-related mortality in the screened population compared to an unscreened population matched for demographics and co-morbidities, not simply a shift to earlier stages at diagnosis.

The reliability of a screening protocol depends on the validity of the measure and the characteristics of the target population. Screening tests are assessed on the basis of four descriptors. 'Sensitivity' and 'specificity' compare the ability of the screening test to assign a positive or negative result relative to the actual presence or absence of the disease (Table 2).

The criteria for positive and negative tests can be adjusted to increase or decrease these values. A test can be made more sensitive by decreasing the threshold for positivity, for example using three red blood cells instead of five per high-power field to define microhaematuria. This changes the test's specificity in the opposite direction, however. Because a bladder cancer diagnosis only can be made with cystoscopy and (usually) biopsy

Table 2: Progression of the disease.

n with a disease & a positive test

Specificity =

true positives

Positive predictive = value

Table 2: Progression of the disease.

n with a disease & a positive test true positives

Specificity =

n with a disease & either a positive or negative test

true positives & false negatives

n without a disease & a negative test

true negatives

n without a disease & either a negative or positive test

true negatives & false negatives

n with a positive test who have the disease

true positives

n with a positive test whether they have the disease or not true positives & false positives

Lead time = the interval from detection because of screening to the time at which diagnosis would have been made without that screening (i.e. when symptoms or signs would have provoked evaluation)

n with a positive test whether they have the disease or not true positives & false positives

Lead time = the interval from detection because of screening to the time at which diagnosis would have been made without that screening (i.e. when symptoms or signs would have provoked evaluation)

Length bias = the tendency of a screening test to preferentially identify indolent disease with a long preclinical sampling phase

(with or without cytology), actual true and false negative rates cannot be ascertained unless all subjects undergo these procedures. Thus, sensitivity and specificity can only been measured in subjects who are cystoscoped regardless of the 'screening' test's results. This limits assessments of these tests to patients with haematuria or prior histories of TCC, in whom cystoscopy is mandatory.

The 'positive' and 'negative' predictive values describe the ability of the screening test to predict the correct diagnostic result (Table 1). These values are also dependent on the threshold for positivity of the screening measure. While a high positive predictive value (i.e. the absence of false positives) connotes an accurate screening modality, it says little about the test's sensitivity, since false negative tests are not considered in the calculation. To optimize the validity of the screening protocol, the target population should have a high prevalence of the disease. By selecting a population with multiple risk factors, such as males over the age of 50 with smoking histories, the likelihood that screening will have many false positives and false negatives are reduced.

Arguments against screening emphasize the consequences of unnecessary diagnosis and treatment. Some diseases, like prostate cancer, are often found incidentally at autopsy, but are not related to the cause of death. Patients do not benefit from aggressive diagnosis or treatment of indolent disease. Bladder cancer, however, is almost never an incidental post-mortem finding because it causes symptoms, leading to evaluation and diagnosis, prior to death.2 This implies that bladder cancer has a brief presymptomatic latency period, and diagnosis before symptoms occur is not a disservice to patients who would have eventually presented at a later time, and possibly later stage, with bladder cancer symptoms.

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