Overall survival and progression-free survival of patients with non-small cell lung cancer and either limited or extensive synchronous metastatic spread in Germany—a population-based cancer registry cohort study

Background: The prognosis of patients with metastatic non-small cell lung cancer (NSCLC) varies considerably depending on the extent and pattern of metastatic spread. While the 8th edition of the tumor-node-metastasis (TNM) classification introduced distinctions between M1a, M1b and M1c stages, further stratification within M1c—particularly regarding the number of organ systems involved—has not been extensively studied in large, unselected cohorts. Therefore, population-based evidence on survival differences with respect to metastatic spread is limited. This retrospective observational study aimed to evaluate overall survival (OS) and progression-free survival (PFS) in NSCLC patients with limited (LMS) or extensive metastatic spread (EMS). Our classification approximates the clinical concepts of oligometastatic and polymetastatic disease, which differ in prognosis and therapeutic approaches. Methods: Data from three German population-based cancer registries were requested for NSCLC patients (ICD-10 C34) diagnosed between 2016 and 2020, aged ≥18 years, with at least one day of follow-up. Only patients with synchronous metastases [Union for International Cancer Control (UICC) stage IV] were included. Metastatic spread was classified according to the 8th edition of the TNM classification and further subclassified according to the number of organ systems involved: intra-thoracic limited metastatic spread (IT-LMS corresponds to M1a), single extra-thoracic limited metastatic spread (ET-LMS corresponds to M1b), limited multi-organ involvement (LMOI corresponds to M1c with ≤3 organs involved), and extensive multiorgan involvement/generalised disease (EMOI corresponds to M1c with >3 organs involved). Descriptive analyses were performed by subgroup. OS and PFS were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors within the LMS cohort. Results: A total of 8,033 patients with synchronous metastatic NSCLC were included. Of these, 7,277 had LMS (IT-LMS: n=1,767; ET-LMS: n=1,314; LMOI: n=4,196) and 756 had EMOI. Median OS ranged from 15 months (IT-LMS) to 4 months (EMOI). Patients with LMOI had significantly better survival than those with more than three organs involved (EMOI, median OS: 8 vs. 4 months). PFS showed a similar gradient. In the limited metastatic cohort, multivariable Cox regression identified age, sex, Eastern Cooperative Oncology Group (ECOG) status, T and N stage, histology and site as independent prognostic factors for OS and PFS. Conclusions: Stratification of synchronous metastatic NSCLC by extent of metastatic spread, including further differentiation within M1c, revealed clear differences in OS and PFS. These findings suggest that the number of organ systems involved may be a clinically relevant parameter and support further evaluation of subclassification approaches in population-based cohorts.