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

Despite substantial benefits of low-dose computed tomography (LDCT) screening, some patients who undergo this screening still die of lung cancer. Factors contributing to LDCT screening "failures" remain unclear. This study hypothesized that specific clinical and demographic factors increase screening failure risk.

The study retrospectively analyzed 16,081 National Lung Screening Trial patients undergoing LDCT screening with initial negative scan results. Screening success was defined as no lung cancer diagnosis or surviving lung cancer treatment. Screening failure included (1) 3 negative scan results followed by death caused by lung cancer, (2) a stage 4 lung cancer diagnosis during the study, or (3) a positive scan result with subsequent death caused by lung cancer. Logistic regression analyses assessed factors associated with screening failure.

Of 15,775 patients (98.1%) with negative screening results who remained cancer-free, 306 cancer cases occurred. Among them, 102 (33.3%) had successful screenings, whereas 204 (66.6%) experienced screening failure. Failure was more common among men, patents aged more than 65 years, and current smokers, with no significant differences by race, ethnicity, or marital status. Multivariable analysis identified higher failure risk associated with age greater than 70 years (odds ratio [OR], 2.65; 95% CI, 1.66-4.12), male sex (OR, 1.56; 95% CI: 1.13-2.17), current smoking (OR, 2.03; 95% CI, 1.52-2.73), chronic obstructive pulmonary disease (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 firefighting (OR, 2.14; 95% CI, 0.99-4.07).

LDCT screening does not prevent all adverse outcomes. Factors such as age, male sex, smoking, chronic obstructive pulmonary disease, emphysema, sarcoidosis, and firefighting increase failure risk. Targeted interventions may enhance effectiveness and reduce mortality.