Reassessing Efficacy: Understanding Failures in Lung Cancer Screening Despite Low-Dose CT Protocol Adherence

V. Shiqi. Wu¹, C. S. Boutros², A. Bassiri³, B. Jiang⁴, J. Sinopoli⁵, L. Tapias⁶, P. Linden³, C. Towe^7
1Case Western Reserve University School of Medicine, Dublin, Ohio ²University Hospitals Cleveland Medical Center/ Case Western Reserve University, University Heights, Ohio ³University Hospitals Cleveland Medical Center, Cleveland, Ohio ⁴University Hospitals Cleveland Medical Center, Strongsville, Ohio ⁵University Hospital Cleveland Medical Center, University Heights, Ohio ⁶University Hospitals Cleveland Medical Center, Shaker Heights, Ohio ⁷University Hospital Cleveland Medical Center, Division of Thoracic Su, Cleveland, Ohio

Purpose: Despite substantial benefits associated with low-dose CT screening (LDCT), some patients still die of lung cancer despite receiving screening. The clinical and demographic factors contributing to these LDCT screening “failures” remain unclear. We hypothesize distinct clinical and demographic factors increase the risk of screening failure.

Methods: We conducted a retrospective analysis of 16,081 patients in the NLST database who underwent LDCT screening and had a negative (normal) first scan (Figure 1). Screening success was defined as having no lung cancer or being diagnosed with lung cancer but remaining alive or dying of other causes. Screening failure was defined by one of the following: (1) three negative screens but dying of lung cancer, (2) a diagnosis of stage 4 lung cancer during the study period, (3) a positive screen but still dying of lung cancer. We performed univariable and multivariable logistic regression analyses to assess the associations between clinicodemographic factors and screening failure.

Results: In the study cohort, 15,775 patients (98.1%) had all negative screenings and remained cancer-free. Of the patients who received a cancer diagnosis (306 patients), 102 patients (33.3%) had a successful screening, and 204 patients (66.6%) experienced screening failure. In univariable analysis, screening failure was associated with male patients (n=144/204; 71% vs. n=9,444/15,877; 59%; p=0.001) and age over 65 (n=79/204; 39% vs. n=3,810/15,877; 24%; p< 0.001). Current smokers were also more prevalent in the screening failure cohort compared to the screening success cohort (n=127; 62% vs. n=7,420; 47%; p< 0.001). The cohorts had no significant race, ethnicity, or marital status differences.
Multivariable analysis identified several factors associated with increased odds of lung cancer screening failure: age over 70 (OR=2.65; 95% CI: 1.66-4.12), male sex (OR=1.56; 95% CI: 1.13-2.17), current smoker (OR=2.03; 95% CI: 1.52-2.73), having chronic obstructive pulmonary disease (COPD) (OR=2.20; 95% CI: 1.35-3.46), emphysema (OR=1.94; 95% CI: 1.27-2.88), sarcoidosis (OR=7.99; 95% CI: 1.24-29.0), and working in firefighting (OR=2.14; 95% CI: 0.99-4.07) (Table 1).

Conclusion: Despite receiving LCDT, more patients die of lung cancer than are successfully screened. In this cohort, factors like increasing age, male sex, current smoking, COPD, emphysema, sarcoidosis, and firefighting work increased screening failure risk. Targeted interventions may be able to enhance screening effectiveness and reduce mortality in these high-risk populations.

Identify the source of the funding for this research project: None