Selecting high-risk individuals for lung cancer screening; the use of risk prediction models vs. simplified eligibility criteria

Abstract

showed a 20% reduction in lung-cancer mortality among long-term heavy smokers screened by low-dose spiral computed tomography (LDCT) compared to standard X-ray diagnostics (1), and the US Prevention Services Task Force (USPSTF) recommends lung cancer screening for all individuals who meet the original NLST eligibility criteria of being 55 to 80 years of age, having smoked 30 or more pack years, and not having quit smoking more than 15 years ago. In Europe, among seven European lung cancer screening trials, jointly including less than 38,000 participants (2) vs. more than 53,000 in the NLST alone, preliminary results from four studies so far did not provide definitive confirmation of a mortality reduction (3-5), but individually these trials were small and lacked statistical power. A final evaluation of the effects on lung cancer mortality in at least three further European trials, including the larger Dutch-Belgian NELSON study (n=7,915 in the screening arm) (6), is expected within the next 1-2 years, as well as a pooled analysis of the European trials. As in the NLST, the eligibility criteria for the European trials were based on age and a simplified index of past cumulative smoking exposure, plus time since quitting for former smokers. The criteria, however, differed from those in the NLST in terms of specific age range, minimum lifetime smoking duration, cumulative smoking exposure (pack years), and maximum time since smoking cessation (7,8) and the criteria varied also across the European trials themselves.At start of the trials, a major motivation for focusing screening on individuals meeting these eligibility criteria was cost. The vast majority of lung cancer cases occur among long-term smokers and at a more advanced age, and focusing on high-risk individuals allows drastic reduction in the number of individuals needed to be screened to identify one case, while still capturing the majority of individuals who develop lung cancer. A further motivation for focusing on high-risk individuals is that it enriches the screened population with participants who may have a benefit from screening (i.e., those who will actually have a screen-detectable lung cancer) while avoiding possible harms to individuals who are unlikely to have a lung tumor. The NLST and the various European trials have now provided extensive documentation not only of the potential benefit of screening, in form of mortality reduction and life years that may be gained by early lung cancer detection, but also of the possible harms. One major type of harm is false-positive diagnoses. In NLST and other trials, depending on the diagnostic criteria (e.g., nodule size) and procedures used for further diagnostic work-up, up to 25% of participants were classified as having suspicious nodules necessitating follow-up examinations, associated with psychologic stress and additional radiation exposure during diagnostic verification. Smaller but still significant

Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers

“…37 A general consensus is emerging that risk-based models outperform and are a better approach for screening compared with USPSTF criteria based on age and smoking alone. [38][39][40] Ultimately, a cost-effective and beneficial approach must be implemented to balance the risks and harms of false-positive screening results, radiation from computed tomography imaging, and overdiagnosis. 40,41 Current lung cancer screening guidelines appear to bias screening toward white persons, excluding highrisk African American individuals and potentially exacerbating disparities in lung cancer outcomes.…”

“…Potential revisions to the minimum age criteria of 50 years could also be considered for African American smokers . A general consensus is emerging that risk-based models outperform and are a better approach for screening compared with USPSTF criteria based on age and smoking alone . Ultimately, a cost-effective and beneficial approach must be implemented to balance the risks and harms of false-positive screening results, radiation from computed tomography imaging, and overdiagnosis .…”

Performance of various risk prediction models in a large lung cancer screening cohort in Gdańsk, Poland—a comparative study

“…Therefore, risk prediction models have gained much attention in recent years (1,13,18,19). The collected evidence indicates that use of high-quality risk stratification models to define the eligibility for lung cancer screening enrollment can-among other benefits-improve the screening efficiency (6).…”

“…With accumulating evidence on both benefits and harms of lung cancer screening, unresolved issues such as optimal selection criteria remain a matter of debate (1,2). Current inclusion criteria based on age and categorized smoking history are derived from the National Lung Screening Trial (NLST) (3).…”

Deciphering the Molecular Profile of Lung Cancer: New Strategies for the Early Detection and Prognostic Stratification

“…In order to improve the cost-effectiveness ratio, several comparative studies of the different criteria for the selection of at-risk populations (i.e., individuals which will largely benefit from the screening) were performed [2,3]. Beside the use of standard eligibility criteria based on age and smoking exposure, the combination of additional risk factors in accurate epidemiological risk models, such as gender, race, ethnicity, education, body mass index, previous or existing lung disease, exposures to dust or asbestos, and personal family history of lung cancer, outperform the eligibility criteria used in previous screening trials [4,5]. Furthermore, minimally invasive strategies, based on radiomics and/or circulating biomarkers, are promising and can complement LDCT to augment the overall performance of screening protocols for lung cancer early detection.…”