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.