Improving Lung Cancer Screening Selection: The HUNT Lung Cancer Risk Model for Ever-Smokers Versus the NELSON and 2021 United States Preventive Services Task Force Criteria in the Cohort of Norway: A Population-Based Prospective Study

Abstract

Background: Improving the method for selecting participants for lung cancer (LC) screening is an urgent need. Here, we compared the performance of the Helseundersøkelsen i Nord-Trøndelag (HUNT) Lung Cancer Model (HUNT LCM) versus the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON)) and 2021 United States Preventive Services Task Force (USPSTF) criteria regarding LC risk prediction and efficiency.

Methods: We used linked data from 10 Norwegian prospective population-based cohorts, Cohort of Norway. The study included 44,831 ever-smokers, of which 686 (1.5%) patients developed LC; the median follow-up time was 11.6 years (0.01-20.8 years).

Results: Within 6 years, 222 (0.5%) individuals developed LC. The NELSON and 2021 USPSTF criteria predicted 37.4% and 59.5% of the LC cases, respectively. By considering the same number of individuals as the NELSON and 2021 USPSTF criteria selected, the HUNT LCM increased the LC prediction rate by 41.0% and 12.1%, respectively. The HUNT LCM significantly increased sensitivity (p < 0.001 and p = 0.028), and reduced the number needed to predict one LC case (29 versus 40, p < 0.001 and 36 versus 40, p = 0.02), respectively. Applying the HUNT LCM 6-year 0.98% risk score as a cutoff (14.0% of ever-smokers) predicted 70.7% of all LC, increasing LC prediction rate with 89.2% and 18.9% versus the NELSON and 2021 USPSTF, respectively (both p < 0.001).

Conclusions: The HUNT LCM was significantly more efficient than the NELSON and 2021 USPSTF criteria, improving the prediction of LC diagnosis, and may be used as a validated clinical tool for screening selection.

Keywords: CONOR; HUNT; Lung cancer screening; Risk prediction models; Screenee selection.

Figure 1

Predictive performance of the HUNT LCM compared against the NELSON and 2021 USPSTF criteria on the CONOR ever-smoker cohort. (A) Comparison of the predictive performance of the HUNT LCM in 6 years by decreasing risk scores (x-axis) against the NELSON and 2021 USPSTF criteria on the CONOR ever-smoker cohort (n = 44831) (red line). The NELSON number of participants by HUNT LCM had a risk score greater than 1.71% in 6 years. The 2021 USPSTF number of participants by HUNT LCM had a risk score greater than 1.16% in 6 years. The HUNT LCM top 16th risk score in the HUNT2 represents the absolute cutoff 0.985% risk in 6 years. Predictive performance analysis of the HUNT LCM using the upper age criterion of the NELSON and 2021 USPSTF criteria including only individuals age younger than 75 and younger than 81 years, respectively. (B) Decreasing HUNT LCM risk score in CONOR ever-smokers from left to right. HUNT LCM risk score 0.01 represents 1% risk of lung cancer in 6 years, 0.02 represents 2% risk, and others. HUNT LCM, HUNT Lung Cancer Model; CONOR, Cohort of Norway; NELSON, Nederlands-Leuvens Longkanker Screenings Onderzoek; USPSTF, United States Preventive Services Task Force.

Figure 2

NNS to identify one case of lung cancer in CONOR. NNS computed when screening the same number of people selected by (A) NELSON criteria (NELSON: age between 50 to 74 years old, >15 cigarettes per day for >25 years or >10 cigarettes per day for >30 years, quit smoking ≤10 years) and (B) 2021 USPSTF criteria (2021 USPSTF: age between 50 to 80 years old, at least 20 pack-years, and currently smoking or quit smoking <15 years). HUNT LCM, HUNT Lung Cancer Model; NSS, number needed to screen; CONOR, Cohort of Norway; NELSON, Nederlands-Leuvens Longkanker Screenings Onderzoek; USPSTF, United States Preventive Services Task Force.

Figure 3

Overall survival from the time of diagnosis to death. Insignificant differences in survival among the individuals in CONOR selected by the HUNT LCM that developed lung cancer in 6 years compared with the TP patients within 6 years predicted by the NELSON and 2021 USPSTF criteria. Kaplan-Meier curves: (A) HUNT LCM versus NELSON criteria. (B) HUNT LCM vs 2021 USPSTF criteria. NELSON criteria include the following: (1) age between 50 to 74 years old; (2) greater than15 cigarettes per day for more than 25 years or greater than 10 cigarettes per day for more than 30 years; and quit smoking less than or equal to 10 years. The 2021 USPSTF criteria include the following: (1) age between 50 to 80 years old; (2) at least 20 pack-years; and (3) currently smoking or quit smoking less than 15 years. HUNT LCM, HUNT Lung Cancer Model; CONOR, Cohort of Norway; USPSTF United States Preventive Services Task Force; FN, false-negative; FP, false-positive; TN, true negative; TP, true positive.

Figure 4

Improving lung cancer prediction of high-risk individuals before CT screening. Cartoon comparing the HUNT LCM against the NELSON and 2021 USPSTF criteria in the CONOR data set of 44831 ever-smokers, in which 222 individuals developed lung cancer within 6 years. The dark gray boxes depict diagnosed lung cancers within the 6 years. The CT boxes on the timeline depict hypothetical screenings. NELSON criteria include the following: (1) age between 50 to 74 years old; (2) greater than15 cigarettes per day for more than 25 years or greater than 10 cigarettes per day for more than 30 years; and quit smoking less than or equal to 10 years. The 2021 USPSTF criteria include the following: (1) age between 50 to 80 years old; (2) at least 20 pack-years; and (3) currently smoking or quit smoking less than 15 years. The HUNT LCM top 16th risk score in the HUNT2 represents the absolute cutoff 0.985% risk in 6 years. CT, computer tomography; HUNT LCM, HUNT Lung Cancer Model. CONOR, Cohort of Norway; NELSON, Nederlands-Leuvens Longkanker Screenings Onderzoek; USPSTF, United States Preventive Services Task Force.