Analysis of lung cancer risk model (PLCO_M2012 and LLP_v2) performance in a community-based lung cancer screening programme

Abstract

<jats:sec><jats:title>Introduction</jats:title><jats:p>Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCO<jats:sub>M2012</jats:sub> and Liverpool Lung Project model (LLP<jats:sub>v2</jats:sub>)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Ever-smokers aged 55–74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCO<jats:sub>M2012</jats:sub> score ≥1.51%) were offered annual LDCT screening over two rounds. LLP<jats:sub>v2</jats:sub> score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>PLCO<jats:sub>M2012</jats:sub> ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLP<jats:sub>v2</jats:sub> ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLP<jats:sub>v2</jats:sub> ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCO<jats:sub>M2012</jats:sub> score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLP<jats:sub>v2</jats:sub> ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLP<jats:sub>v2</jats:sub> ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); p&lt;0.0001). Adverse measures of health, including airflow obstruction, respiratory symptoms and cardiovascular disease, were positively correlated with LC risk. Coronary artery calcification was predictive of LC (<jats:sub>adj</jats:sub>OR 2.50, 95% CI 1.11 to 5.64; p=0.028).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Prospective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCO<jats:sub>M2012</jats:sub> model may underestimate risk in deprived UK populations; further research focused on model calibration is required.</jats:p></jats:sec>

Personalising lung cancer screening: An overview of risk‐stratification opportunities and challenges

“…52,54 Consequently, older individuals and those with greater smoking exposures are more likely to be identified as being at 54 Prospective studies and pilots which enrolled screenees based on risk-prediction models indeed showed that the mean age and presence of comorbidities increased in the higher risk-groups. 88,89 However, the average age in these studies and pilots was around 65, at which the life-expectancy is 18-22 years. 90 In these studies, self-selection and physician-selection may have aided in reducing the uptake of screening in individuals with low life-expectancies; but within large-scale programs, the uptake of screening in individuals with limited lifeexpectancies may still be considerable.…”

“…But, if individuals with limited life‐expectancies (<5 years) are excluded from screening, overdiagnosis could be substantially reduced (by over 65%) while moderately reducing the number of screens required (10%‐13% fewer) and retaining the life‐years gained by risk‐based screening 54 . Prospective studies and pilots which enrolled screenees based on risk‐prediction models indeed showed that the mean age and presence of comorbidities increased in the higher risk‐groups 88,89 . However, the average age in these studies and pilots was around 65, at which the life‐expectancy is 18‐22 years 90 .…”

“…Manchester Lung Health Check Pilot: 1.51% risk‐threshold 88,164 …”

Implementation of lung cancer screening: what are the main issues?

“…Risk-prediction models have since also been used to identify eligible individuals in various trials and implementation pilots. The UK Lung Screen (UKLS) trial or the NLST-criteria in ever smokers (aged 55-74) from deprived areas showed significant variation in selecting those eligible for lung cancer screening between these different methods (41). Furthermore, risks for developing lung cancer will vary per person over time, due to changes in risk factors as smoking history, but also age.…”

Targeting lung cancer screening to individuals at greatest risk: the role of genetic factors

“… 57 Retrospective analysis found that within the group of patients with cancer diagnosed, PLCO M2012 and LLP v2 at a ≥2.5% risk threshold would have outperformed NLST generalised eligibility criteria that would have missed 18% of cancers. 58 Based on the success of this pilot, NHS England have commissioned a further 10 screening pilots across the country. 59…”