Selecting lung cancer screenees using risk prediction models-where do we go from here

Abstract

The National Lung Screening Trial (NLST) demonstrated that low dose computed tomography (LDCT) screening could reduce lung cancer mortality by 20% in high-risk individuals. The United States Preventive Services Task Force (USPSTF) and Centers for Medicare and Medicaid Services (CMS) approved lung cancer screening. The NLST, USPSTF and CMS define high risk as smoking ≥30 pack-years, smoking within the past 15 years, and being ages 55-74, 55-80 or 55-77. Retrospective studies demonstrated selection using model-estimated risk is superior to NLST-like criteria: higher sensitivity and positive predictive value (PPV), more deaths averted and higher cost-effectiveness. Projects are underway that may additionally support use of risk to determine eligibility. Firstly, the International Lung Screen Trial (ILST) is prospectively enrolling 4,000 individuals for screening if individuals have PLCOm2012 model risk ≥1.5% or are USPSTF+ve. Six-year follow-up will allow comparisons. Interim results support the risk approach. Secondly, Cancer Care Ontario started the Lung Cancer Screening Pilot for People at High Risk in order to find optimal design for province-wide programmatic screening. They are enrolling 3,000 individuals to screening based on PLCOm2012 risk ≥2%. Some hesitation to recommend screening selection based on model risk comes from the observation that selected individuals are older, have more comorbidities, are expected to have fewer life years and quality-adjusted life years (QALY) and are more likely to die from competing causes. We show that 25.6% of NLST eligible smokers are at low risk (6-year lung cancer incidence proportion =0.008). This group will not benefit from screening but has lower age, fewer comorbidities and fewer competing causes of death. When they are excluded from the NLST+ve group, age, comorbidity count and competing causes of death are similar to those in the PLCOm2012+ve group. In some jurisdictions, model-based lung cancer screening selection needs to take into consideration the elevated risk in blacks and indigenous peoples.

Keywords: Lung cancer screening; risk models; risk prediction.

Figure 1

Lung cancer mortality rates in NLST intervention arms by PLCOm2012 model risks. NLST, National Lung Screening Trial; NNS, number needed to screen to avert 1 lung cancer death; PLCOm2012, the lung cancer risk prediction model described in reference (7). Adapted from reference (1).

Figure 2

Mean age, mean comorbidity count and number of competing causes of death in 5 years per 1,000 individuals in PLCO smokers who are NLST criteria positive (NLST+), have PLCOm2012 model risk ≥1.5% (PLCOm2012+), and who are NLST+ but have low risk individuals (PLCOm2012 <1.5%) excluded. Comorbidity Count, heart disease + stroke + history of cancer + hypertension + chronic obstructive pulmonary disease/emphysema + diabetes. NLST, National Lung Screening Trial; PLCO, Prostate Lung Colorectal and Ovarian Cancer Screening Trial.