Improving selection criteria for lung cancer screening. The potential role of emphysema

Abstract

Rationale: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity.

Objectives: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion.

Methods: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema.

Measurements and main results: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%.

Conclusions: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.

Keywords: National Lung Screening Trial; emphysema; low-dose computed tomography; lung cancer screening.

Figure 1.

Lung cancer distribution in each of the original cohorts (P-IELCAP [left] and PLuSS [right]), compared with the distribution after NLST criteria are applied. LC = lung cancer; LDCT = low-dose computed tomography; NLST = National Lung Screening Trial; P-IELCAP = Pamplona International Early Lung Cancer Detection Program; PLuSS = Pittsburgh Lung Screening Study.

Figure 2.

(A and B) Lung cancer distribution after applying different intermediate selection criteria following the baseline screening round, limiting successive screening rounds to those with emphysema in the original cohorts (P-IELCAP[E] and PLuSS[E]), those who met NLST criteria only, and those who met NLST criteria or had emphysema, independent of NLST (NLST/E). (A) P-IELCAP; (B) PLuSS. LC = lung cancer; LDCT = low-dose computed tomography; NLST = National Lung Screening Trial; P-IELCAP = Pamplona International Early Lung Cancer Detection Program; PLuSS = Pittsburgh Lung Screening Study.

Figure 3.

Lung cancer ascertainment in P-IELCAP (solid squares) and PLuSS (open squares) in terms of number of participants screened according to the strategy used: NLST, NLST/E, P-IELCAP(E), or PLuSS(E). The data are normalized for each cohort; “1.00” represents 100% of the participants in each cohort (x-axis) or the total number of lung cancers (y-axis). (E) suffix = limitation of annual low-dose chest computed tomography in NLST, P-IELCAP, and PLuSS to individuals with emphysema; NLST = National Lung Screening Trial; NLST/E = extended NLST subcohort including individuals with emphysema independent of NLST; P-IELCAP = Pamplona International Early Lung Cancer Detection Program; PLuSS = Pittsburgh Lung Screening Study.