Survival Time

| = Life Extended figure 12.3. Lead time bias.

detected by screening with those whose cancer was detected clinically are flawed. The important issue with screening is whether there is a "situation 3," in which people's lives have actually been extended. The best study design to avoid this bias is the randomized controlled trial.

A second bias also may cause people to conclude that screening is useful when it is not. This bias, termed "length-biased sampling" (or "length-time bias"), is associated with the heterogeneity of cancer growth rates and malignant potential (Figure 12.4). Patients 1 and 4 in the figure have rapidly progressive tumors that spend relatively little time in the "detectable preclinical phase" area. As a result, these cancers are often missed by screening tests. Patients 2 and 3, however, have slower-growing, less-malignant cancers that are less likely to be fatal. These cancers spend a longer time in the detectable preclinical phase area and thus are more likely to be detected by screening. Thus, length-biased sampling makes us believe that screening is effective because people with screening-detected cancers do better than people with clinically detected cancers. Slower-growing and less-malignant cancers are preferentially detected by screening programs.

Interestingly, patient 4, whose cancer was detected at a later age, does not die of his or her cancer, even though the cancer is faster growing and malignant, because of competing risks: he or she is more likely to die of another cause at this older age. Patient 4 is not helped by screening.

Death From Cancer /Patient 1

Symptomatic Phase/

: Detection Screening

De Pre

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t Patient 3

Patient 2

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