Burden and trends in subsequent primary lung cancer incidence by sex in the United States

Lung Cancer. 2025 Jun 18:205:108625. doi: 10.1016/j.lungcan.2025.108625. Online ahead of print.

Abstract

Introduction: Despite well-documented sex and age differences in lung cancer incidence and trends, it remains unclear whether the patterns differ by tumor sequence. This study compares sex- and age-specific incidence patterns of first primary lung cancers (FPLCs) and subsequent primary lung cancers (SPLCs) in the US.

Methods: Lung and bronchus (hereafter, lung) cancers diagnosed from 2001 to 2021 (ages, 20+ years) were identified from the U.S Cancer Statistics Public Use Database. Age-standardized incidence rates and female-to-male incidence rate ratios (RRs) were calculated for FPLC and SPLC, separately, overall and stratified by age groups (20-49, 50-59, 60-69, 70-79, 80+ years) and diagnosis years (2001-2006, 2007-2011, 2012-2016, 2017-2021).

Results: From 2001 to 2021, there were 3,494,840 FPLC and 1,017,025 SPLC diagnoses. Overall, the incidence rate was 27% lower in women than in men (57.51 versus 78.56 per 100,000) for FPLCs and 32% lower for SPLCs (16.65 versus 24.54 per 100,000). However, the sex gap narrowed at younger ages, with female predominance more pronounced for SPLCs than for FPLCs. Specifically, among ages 20-49, SPLC incidence was 88% higher in women (0.81 vs. 0.43 per 100,000; RR = 1.88, 95% confidence interval [CI] = 1.82-1.94) and, among ages 50-59, it was 26% higher (10.89 vs. 8.63 per 100,000; RR = 1.26, 95% CI = 1.25-1.28), in contrast to comparable or higher rates in males for FPLCs. The female predominance was consistent throughout 2001-2021 for SPLCs (ages, 20-59), whereas it emerged only since 2012-2016 for FPLCs (ages, 20-49).

Conclusion: Sex-specific lung cancer incidence considerably differs by tumor sequence. The female predominance of SPLC among young adults highlights the need for analytical studies to identify risk factors and has important implications for young adult cancer survivorship.

Keywords: Cancer survivors; Incidence; Lung cancer; Second primary lung cancer; Sex difference.