Low positive predictive value of computed tomography screening for lung cancer irrespective of commonly employed definitions of target population

Abstract

Screening for lung cancer (LC) by low-dose computed tomography (LDCT) has been demonstrated to reduce LC mortality in randomized clinical trials (RCTs), and its implementation is in preparation in many countries. However, definition of the target population, which was based on various combinations of age ranges and definitions of heavy smoking in the RCTs, is subject to ongoing debate. Using epidemiological data from Germany, we aimed to estimate prevalence of preclinical LC and positive predictive value (PPV) of LDCT in potential target populations defined by age and smoking history. Populations aged 50 to 69, 55 to 69, 50 to 74 and 55 to 79 years were considered in this analysis. Sex-specific prevalence of preclinical LC was estimated using LC incidence data within those age ranges and annual transition rates from preclinical to clinical LC obtained by meta-analysis. Prevalence of preclinical LC among heavy smokers (defined by various pack-year thresholds) within those age ranges was estimated by combining LC prevalence in the general population with proportions of heavy smokers and relative risks for LC among them derived from epidemiological studies. PPVs were calculated by combining these prevalences with sensitivity and specificity estimates of LDCT. Estimated prevalence of LC was 0.3% to 0.5% (men) and 0.2% to 0.3% (women) in the general population and 0.8% to 1.7% in target populations of heavy smokers. Estimates of PPV of LDCT were <20% for all definitions of target populations of heavy smokers. Refined preselection of target populations would be highly desirable to increase PPV and efficiency of LDCT screening and to reduce numbers of false-positive LDCT findings.

Keywords: lung cancer; pack-years; preclinical cancer; predictive value; screening.