Clinicopathological characteristics associated with intrapulmonary metastasis rather than single primary lung cancer at first diagnosis: a study based on the Surveillance, Epidemiology, and End Results database using Bayesian networks and structural equation modeling.

Background: At initial lung cancer diagnosis, intrapulmonary metastasis (IPM) usually reflects more advanced intrathoracic disease than single primary lung cancer (SPLC). However, the clinical and pathological characteristics associated with presenting as IPM rather than SPLC, and with more extensive IPM patterns, are not well described. This study aimed to characterise how sociodemographic and tumor features at diagnosis are associated with IPM compared with SPLC and with different intrapulmonary metastatic patterns in a large population-based registry. Methods: We conducted a cross-sectional analysis of patients with non-small cell lung cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019. IPM and SPLC were defined using the "Separate Tumor Nodules Ipsilateral Lung" recode. Bayesian network modeling and structural equation modeling were used to describe conditional association structures among sociodemographic variables, tumor characteristics, and lung cancer type. Simulated interventions in the Bayesian network yielded model-based risk ratios (RRs) with 95% confidence intervals (CIs) for IPM versus SPLC. Logistic regression was used in an exploratory subgroup analysis of IPM patterns comparing disease confined to the same lobe, disease in different lobes, and disease in both the same and different lobes. Results: Among 45,194 patients, 9,302 had IPM and 35,892 had SPLC. In the Bayesian network, tumor grade and laterality showed the strongest direct associations with lung cancer type, and the model discriminated IPM from SPLC with an area under the curve of 0.919. Sociodemographic variables showed weaker and less consistent associations with lung cancer type after adjustment for tumor characteristics. Simulated interventions suggested progressively higher model-based risk of IPM with poorer differentiation (RR of well-differentiated to poorly differentiated grade: 1.664, 95% CI: 1.571-1.772) and with right-sided disease (RR of right-sided to left-sided disease: 1.136, 95% CI: 1.093-1.178). In subgroup analyses, higher grade and lower and middle lobe location were associated with IPM patterns involving multiple lobes. Conclusions: In this large registry-based study, intrapulmonary metastatic disease at first lung cancer diagnosis was more strongly associated with tumor differentiation, laterality, and anatomical distribution than with measured sociodemographic factors. These observational associations may help characterise patients who present with more extensive intrapulmonary disease.