Evaluation of the accuracy of the PLCOm2012 6-year lung cancer risk prediction model among smokers in the CARTaGENE population-based cohort.

Background: The PLCO_m2012 prediction tool for risk of lung cancer has been proposed for a pilot program for lung cancer screening in Quebec, but has not been validated in this population. We sought to validate PLCO_m2012 in a cohort of Quebec residents, and to determine the hypothetical performance of different screening strategies.

Methods: We included smokers without a history of lung cancer from the population-based CARTaGENE cohort. To assess PLCO_m2012 calibration and discrimination, we determined the ratio of expected to observed number of cases, as well as the sensitivity, specificity and positive predictive values of different risk thresholds. To assess the performance of screening strategies if applied between Jan. 1, 1998, and Dec. 31, 2015, we tested different thresholds of the PLCO_m2012 detection of lung cancer over 6 years (1.51%, 1.70% and 2.00%), the criteria of Quebec's pilot program (for people aged 55-74 yr and 50-74 yr) and recommendations from 2021 United States and 2016 Canada guidelines. We assessed shift and serial scenarios of screening, whereby eligibility was assessed annually or every 6 years, respectively.

Results: Among 11 652 participants, 176 (1.51%) lung cancers were diagnosed in 6 years. The PLCO_m2012 tool underestimated the number of cases (expected-to-observed ratio 0.68, 95% confidence interval [CI] 0.59-0.79), but the discrimination was good (C-statistic 0.727, 95% CI 0.679-0.770). From a threshold of 1.51% to 2.00%, sensitivities ranged from 52.3% (95% CI 44.6%-59.8%) to 44.9% (95% CI 37.4%-52.6%), specificities ranged from 81.6% (95% CI 80.8%-82.3%) to 87.7% (95% CI 87.0%-88.3%) and positive predictive values ranged from 4.2% (95% CI 3.4%-5.1%) to 5.3% (95% CI 4.2%-6.5%). Overall, 8938 participants had sufficient data to test performance of screening strategies. If eligibility was estimated annually, Quebec pilot criteria would have detected fewer cancers than PLCO_m2012 at a 2.00% threshold (48.3% v. 50.2%) for a similar number of scans per detected cancer. If eligibility was estimated every 6 years, up to 26 fewer lung cancers would have been detected; however, this scenario led to higher positive predictive values (highest for PLCO_m2012 with a 2.00% threshold at 6.0%, 95% CI 4.8%-7.3%).

Interpretation: In a cohort of Quebec smokers, the PLCO_m2012 risk prediction tool had good discrimination in detecting lung cancer, but it may be helpful to adjust the intercept to improve calibration. The implementation of risk prediction models in some of the provinces of Canada should be done with caution.