Clinical outcomes and neuroendocrine features of transformed versus primary small-cell lung cancer

INTRODUCTION: The clinical outcomes of transformed small-cell lung cancer (T-SCLC) was previously considered comparable with primary SCLC (P-SCLC). However, whether T-SCLCs and P-SCLCs differ in the era of immunotherapy remains unclear. METHODS: Clinical outcomes were retrospectively analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method and Cox regression. Linear correlation and regression analyses were used to assess prognostic value of baseline neuron-specific enolase (NSE). Hierarchical clustering was used to group neuroendocrine (NE) markers of T-SCLC by immunohistochemical results. RESULTS: Between March 2018 and March 2023, 206 patients with T-SCLC (n = 42) and P-SCLC (n = 164) were enrolled in the study. The median OS (mOS) of T-SCLC cohort was significantly shorter than that of the P-SCLC cohort (11.7 vs. 12.9 months, P = 0.033). In the T-SCLC cohort, the mOS of chemoimmunotherapy significantly outlasted that of chemotherapy (15.4 vs. 8.5 months, P = 0.001). The optimal baseline NSE cutoff values differed between T-SCLC (19.7 ng/ml) and P-SCLC (74.8 ng/ml), and a high NSE level was associated with poorer mOS in both T-SCLC (10.0 vs. 16.5 months, P = 0.003) and P-SCLC (10.8 vs. 16.5 months, P < 0.001). The cluster with stronger expression of NE markers in T-SCLC exhibited longer mOS (14.3 vs. 10.3 months, P = 0.030). CONCLUSION: T-SCLC had a statistically poorer prognosis than P-SCLC, but the difference was modest. Chemoimmunotherapy might improve the outcomes of T-SCLC. Patients with T-SCLC who show stronger neuroendocrine features may have a poorer prognosis.