Evidence of Benefit
Three other randomized trials have been conducted. The Mayo Lung Project (MLP) was initiated in 1971 and involved males aged 45 years or older who were heavy smokers.[14,15,16] Patients free of lung cancer on initial screening were randomly assigned to be offered screening with sputum cytology and chest x-ray every 4 months or to a group merely advised once at baseline to seek screening annually. At Johns Hopkins University [17,18,19,20] and Memorial Sloan-Kettering Cancer Center,[21,22] individuals were randomly assigned to intervention and control groups, which were both offered annual chest x-ray. In addition, the intervention group was offered sputum cytology every 4 months. None of the three trials reported a reduction in lung cancer mortality in the more intensively screened study group compared with the control group. Extension of follow-up to a median of 20.5 years in the MLP did not alter this conclusion. The sustained excess of incident cases of lung cancer in the screened versus unscreened arms of the MLP during long-term follow-up, in the absence of evidence of a reduction in mortality, suggests that chest x-rays resulted in overdiagnosis of lung cancer.
The Mayo trial is the most pertinent study for assessing annual x-ray screening because the use of screening x-rays differed in the two arms. There are several reservations about the Mayo study. The study was designed to detect a 50% reduction in lung cancer mortality and had insufficient power to demonstrate a lesser but medically important reduction of 10% to 15%. Also, about 50% of men in the control group received an annual chest x-ray, so that contamination may have been sufficient to obscure an effect. Therapeutic advances may render early detection more effective today. Additionally, the spectrum of lung cancer type has shifted during the last two decades. Whereas the most common type used to be squamous cell cancer (usually centrally located), the most common type is now adenocarcinoma (usually peripherally located). The latter may be more amenable to early detection by chest x-ray. In contrast, sputum cytology is more sensitive in the detection of squamous cell cancer than in detecting adenocarcinoma.[25,26]
There is no good evidence that screening for lung cancer using chest x-ray or sputum cytology can reduce lung cancer mortality. Sputum cytology has not been shown to be effective when used as an adjunct to annual chest x-ray. Screening with chest x-ray plus sputum cytology appears to detect lung cancer at an earlier stage, but this would be expected in a screening test whether or not it was effective at reducing mortality. Similarly, case survival was improved relative to cases diagnosed through usual care, but this may simply reflect lead-time bias or overdiagnosis bias. No reduction in lung cancer mortality has been observed.