Incidence Patterns and Prognostic Impact of Lung-Involving Multiple Primary Cancers: A 10-Year Hospital-Based Cohort...

Multiple primary cancers (MPCs) are increasingly recognized among lung cancer survivors; however, incidence patterns and prognostic impact of lung-involving MPCs (MPC-LC) remain incompletely characterized, particularly given substantial competing mortality. This study aimed to quantify MPC-LC burden and patterns, identify predictors of incident MPC following lung cancer diagnosis, and evaluate factors associated with overall survival.

Patients diagnosed with lung cancer between 2013 and 2022 at Korea Cancer Center Hospital were retrospectively analyzed. MPCs were ascertained using Surveillance, Epidemiology, and End Results multiple-primary rules and classified by synchronicity and sequence. Incident metachronous MPCs (mMPC) following lung cancer diagnosis were evaluated using landmark Fine-Gray models, with death as a competing event. OS was assessed using multivariate time-varying Cox models with landmark and lag-time sensitivity analyses.

MPC-LC was detected in 317 of 3195 patients (9.9%; 99 synchronous, 218 metachronous). The 3- and 5-year cumulative incidence of mMPC was 7.3% and 9.6%, respectively, whereas competing mortality was 56.2% and 77.0%. Although unadjusted Kaplan-Meier estimates suggested longer crude survival in patients with MPC-LC, time-aware analyses demonstrated an association between MPC-LC and increased mortality, persisting across inverse probability of treatment weighting and sensitivity analyses. Advanced or unknown stage and neuroendocrine carcinoma histology were adverse prognostic factors.

MPC-LC occurs amid substantial competing mortality, and its prognostic impact is best understood using bias- and time-aware analytical approaches. These findings support stage- and histology-informed surveillance and coordinated multidisciplinary care in thoracic oncology.