Rationale: Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. Objectives: To explore the effect of screening with low-dose spiral CT (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability. Methods: Male subjects, aged 60-75, smokers of 20+ pack-years were randomized to screening with low-dose spiral CT or control. All participants underwent a baseline, once-only chest X-ray (CXR) and sputum cytology examination. Screening-arm subjects had LDCT upon accrual, to be repeated every year for four additional years, while controls had a yearly medical examination only. Measurements and Main Results: 2811 subjects were randomized and 2472 were enrolled (LDCT 1276, control 1196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) LDCT patients and 34 (2.8%) controls (p=0.016). Resectability rates were similar in both groups. More patients with Stage I disease were detected by spiral CT (54% vs 34%, p=0.06) and less cases were detected due to intercurrent symptoms in the screening arm. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty LDCT patients (1.6%) and 20 controls (1.7%) have died of lung cancer, while 26 and 25 respectively have died of other causes. Conclusions: The mortality benefit from lung cancer screening by spiral CT might be far smaller than anticipated.

Clinical Trials Registry information: NCT00420862, at www.clinicaltrials.gov.