Association between metastatic site and survival in non–small cell lung cancer: A SEER-based cohort study.

e20658 Background: The recently updated 9th edition TNM staging system is the most widely used prognostic tool for non-small cell lung cancer (NSCLC). However, it does not incorporate the specific site of distant metastasis. Data are limited on whether survival differs by metastatic site among patients diagnosed with stage IV NSCLC with single-organ metastatic involvement. Methods: We queried the Surveillance, Epidemiology and End Results (SEER) database for adults with metastatic NSCLC and single-organ metastasis at diagnosis, using SEER Research Plus Data (17 Registries, November 2023 submission). Cancer-specific survival (CSS) was estimated using Kaplan–Meier methods, and differences between metastatic sites were compared using the log-rank test. Patients were categorized by metastatic site as lung, distant lymph node, brain, bone, liver, or other. Multivariable Cox proportional hazards models were used to evaluate associations between metastatic site and overall survival (OS) and CSS. Lung metastasis was used as the reference group. Models adjusted for age, race, biological sex, marital status, and receipt of chemotherapy, radiation therapy, and surgery. Results: A total of 18,489 eligible patients with metastatic NSCLC and single-organ involvement were identified, including 4,709 squamous and 13,780 nonsquamous cases. The median age was 68.4 years, and 53% of patients were male. Among patients with nonsquamous NSCLC, liver metastasis was associated with the worst OS (HR 1.915; 95% CI 1.671–2.195; P&lt;0.001) and CSS (HR 1.933; 95% CI 1.670–2.237; P&lt;0.001) compared with lung metastasis. In contrast, among patients with squamous NSCLC, brain metastasis was associated with the worst OS (HR 1.966; 95% CI 1.712–2.258; P&lt;0.001) and CSS (HR 2.176; 95% CI 1.881–2.516; P&lt;0.001) compared with lung metastasis. Conclusions: Among patients with metastatic NSCLC and similar TNM stage, the site of single-organ metastasis is associated with OS and CSS, and these associations differ between squamous and nonsquamous histology. Incorporating metastatic site may improve risk stratification beyond TNM staging in stage IV NSCLC. Adjusted hazard ratios for OS and CSS by metastatic site in single-organ metastatic NSCLC. Metastatic location CCS OS squamous NSCLC Lung 1 - - 1 - - Distant lymph node 1.133 0.939-1.368 0.19 1.075 0.901-1.282 0.42 Brain 2.176 1.881-2.516 &lt;.001 1.966 1.712-2.258 &lt;.001 Bone 1.799 1.597-2.027 &lt;.001 1.698 1.52-1.898 &lt;.001 Other 1.44 1.280-1.621 &lt;.001 1.385 1.241-1.546 &lt;.001 Liver 1.502 1.290-1.753 &lt;.001 1.424 1.234-1.643 &lt;.001 Nonaqueous NSCLC Lung 1 - - 1 - - Distant lymph node 1.049 0.902-1.219 0.54 1.04 0.904-1.198 0.58 <jats:td colspa