Background: Assessment of salvage treatment for newly developed metastases in patients previously treated with curative-intent concurrent chemoradiation (cCRT) +/- immune checkpoint inhibition (ICI) for unresectable stage III NSCLC. Methods: We analysed data of 136 patients treated from 2011 to 2020 in as single tertiary cancer centre. Location of first observed distant metastasis (DM) were categorized as brain/intracranial metastasis (BM), organ metastasis (OM) and skeletal metastasis (SM). Treatment with radiotherapy (RT) and systemic therapy (ST); sub-divided into chemo- (CT), immuno (IT) and tyrosine kinase inhibitor therapy (TKI) was assessed. Results: All patients received definitive cCRT ≥ 60 Gy with 2 courses of chemotherapy. Thirty-six (26%) patients received ICI. Median follow-up was 49.7 months, median PFS was 9.9 (95%CI: 7.0-12.7) months, 12- and 24-month PFS-rates were 42% and 29%, respectively. Median OS was 31.2 months (95% CI 16.9 – 45.6), 12- und 24-month-OS-rates were 74% und 53%. Sixty-one patients (45%) developed metastasis: 21 (15%) BM, 20 (15%) OM und 20 (15%) SM. Median OS of patients with BM, OM and SM was 27.4, 25.5 and 17.9 months, respectively (p = 0.821). In total 45/61 patients were initially treated with cCRT and 16 with cCRT+ICI. Median OS was 26.5 (cCRT+ICI) vs. 23.4 (cCRT) months (p = 0.121); 12- and 24- month survival rates were 94% vs. 64% and 63% vs. 47%. Patients with SM survived significantly longer, if the initial treatment included ICI (Median not reached vs. 7.5 months; p = 0.042). Fifty-three (87%) of 61 patients received the following salvage therapy: 28 (53%) RT, 10 (19%) ST and 15 (28%) combined RT + ST. Patients with SM showed a trend towards longer OS after RT-alone (p = 0.069). Thirteen patients with adenocarcinoma received ST: 7 CT and 6 TKI with a significant longer OS (40.1 months TKI vs. 12.1 months CT; p = 0.040). All 21 patients with BM were treated with RT. Patients treated with stereotactic radiosurgery (SRS) showed a significant longer OS of 40.1 months vs. 12.2 months for patients treated with whole brain radiotherapy (WBRT) (p = 0.016). Conclusions: Patients with SM had a significantly longer OS if their initial therapy consisted of cCRT+ICI vs. cCRT alone. Patients with BM as first site of metastasis had a significantly longer OS when treated with SRS vs. WBRT. Salvage treatment with TKI resulted in a significantly longer OS compared to salvage CT in patients with adenocarcinomas.