Association of baseline hormone levels with outcomes of first-line immunotherapy in extensive-stage small cell lung cancer.

BACKGROUND

Endocrine dysregulation may influence immune function and clinical outcomes in cancer. This study investigated the prognostic relevance of baseline endocrine hormones in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line immunotherapy.

METHODS

This retrospective multicenter cohort study included patients with ES-SCLC treated at multiple centers between January 2020 and December 2024. Baseline serum levels of cortisol, adrenocorticotropic hormone (ACTH), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured before treatment. Patients were stratified into high and low groups for each hormone based on median values. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models.

RESULTS

A total of 377 patients were included, with a median PFS of 9.7 months and median OS of 16.7 months. Patients with high baseline cortisol had significantly shorter PFS (8.9 vs. 11.7 months, P=0.02) and OS (15.2 vs. 26.0 months, P=0.003). Elevated cortisol remained independently associated with inferior survival after multivariable adjustment [hazard ratio (HR) =1.540, 95% confidence interval (CI): 1.04-2.15, P=0.03]. In contrast, baseline ACTH, FT3, FT4, and TSH were not significantly associated with PFS or OS.

CONCLUSIONS

Baseline cortisol is independently associated with survival outcomes in ES-SCLC patients receiving immunotherapy and may serve as a prognostic biomarker. These findings highlight the relevance of neuroendocrine-immune interactions and warrant prospective validation.