Prognostic Impact of Organ-Specific Metastasis in Non-Small-Cell Lung Cancer.

Purpose: Prognostic stratification is essential in non-small-cell lung cancer (NSCLC) to guide treatment decisions. While the TNM staging system has evolved to refine the M category based on metastatic burden, it does not account for differences in prognosis based on the specific organ affected. This study evaluates whether incorporating organ-specific metastasis improves prognostic discrimination in stage IV NSCLC.

Materials and methods: We conducted a retrospective cohort study using data from the Korean Central Cancer Registry (2014-2018). Patients with stage IV NSCLC were classified according to the 9th edition TNM classification: M1b (single-organ, single metastasis), M1c1 (multiple metastases within a single organ), and M1c2 (multiple organ metastases). Survival outcomes were compared across groups using Kaplan-Meier analysis and Cox proportional hazards modeling.

Results: Among 3,165 patients, 56.5% had single-organ metastases, while 43.5% had multiple organ metastases. Median overall survival (OS) was longest in M1b (8.0 months), followed by M1c1 (6.0 months), and shortest in M1c2 (5.9 months) (p<0.001). However, survival varied by metastatic organ. Liver, adrenal, and uncommon-site metastases were associated with significantly worse OS, even among M1b patients. Some M1b and M1c1 patients with high-risk organ metastases had worse survival than M1c2 patients, challenging the TNM-defined prognostic hierarchy.

Conclusion: The current TNM M category does not fully capture the prognostic impact of metastatic organ involvement. Incorporating organ-specific metastases into staging and prognostic models could refine risk stratification and improve personalized treatment approaches for stage IV NSCLC.