MEASURING EFFECTIVENESS OF LUNG-CANCER SCREENING - FROM CONSENSUS TO CONTROVERSY AND BACK

Background: While intense controversy exists regarding screening for b reast, colorectal, and prostate cancer, a consensus exists regarding l ung cancer screening. All organizations recommend against any efforts to detect early lung cancer because each of four randomized controlled trials (RCTs) has failed to demonstrate a significant reduction in lu ng cancer mortality as a result of screening. Synthesis: Disease-speci fic mortality is assumed to represent the best measure of screening ef fectiveness in RCTs, because it is not subject to confounding by lead time, length, or overdiagnosis biases. However, the effects of these b iases are predictable, so accurate assessments of the degree of confou nding by these biases can be made. Moreover, the ability of mortality to accurately reflect cancer death rates depends on the ability of ran domization to create experimental and control populations that have an equal risk of dying of the disease under study, except insofar as ear ly detection may reduce that risk. Because the majority of participant s in screening trials never develop the disease under investigation, s mall absolute differences in disease risk between groups often persist despite randomization, and such differences translate into much large r proportional differences in the size of subgroups at risk for diseas e-specific mortality. This effect confounds the ability of disease-spe cific mortality to accurately measure screening effectiveness. Results : A total of 18 RCTs have been conducted to evaluate screening for bre ast, colorectal, and lung cancer. In the only two RCTs that reported a significant mortality reduction for screening mammography in breast c ancer, and in the one RCT that reported a significant mortality reduct ion for fecal occult blood screening in colorectal cancer, population differences led mortality comparisons to overestimate the effectivenes s of screening. In lung cancer, no significant mortality reductions ha ve been reported (to my knowledge), but in the two RCTs most directly addressing the effectiveness of chest radiograph (CXR) screening, popu lation differences led mortality comparisons to underestimate the abil ity of CXRs to reduce the risk of crying of lung cancer. Although mort ality is believed to be the best measure of outcome, not a single exam ple can be cited as definitive proof of efficacy for any screening str ategy. Thus, screening cannot be recommended for any cancer on the bas is of consistent reductions in mortality in RCTs. Analysis: Current po licy, which calls for no early detection efforts for lung cancer, impl icitly accepts the validity of two contradictory assertions. Conventio nal wisdom maintains that lung cancer is a highly virulent disease and that metastases are present: at inception; accordingly, early detecti on is ineffective. However, RCTs suggest that lung cancer is an indole nt disease and that radiographically detected lesions are clinically u nimportant; accordingly, early detection is unnecessary. Such contradi ctions mandate some rethinking of the fundamental assumptions underlyi ng screening evaluation. Conclusions: Considerable evidence suggests t hat annual CXR screening could result: in a dramatic reduction in lung cancer mortality in our society. However, proper interpretation of th e data depends completely on how screening effectiveness is measured. Given the enormous public health importance of this issue, a consensus conference is recommended to determine whether lung cancer screening can save lives.