Abstract
BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy is the standard first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, predictive biomarkers for treatment efficacy are lacking. This study aimed to investigate the association between clinical characteristics, particularly liver metastasis, and survival outcomes in patients with ES-SCLC treated with chemoimmunotherapy. METHODS: We conducted a retrospective analysis of 279 patients with ES-SCLC treated at the Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (102 receiving chemoimmunotherapy and 177 receiving chemotherapy alone). The association of clinical features with progression-free survival (PFS) and overall survival (OS) was assessed via Cox regression. Furthermore, a meta-analysis of five randomized controlled trials (IMpower133, CAPSTONE-1, CASPIAN, ETER701, and RATIONALE-312) was performed to confirm the effect of liver metastases on the efficacy of chemoimmunotherapy. RESULTS: The cohort of 279 patients with ES-SCLC was predominantly male (92.1%), and the vast majority had a smoking history (85.7%). The median age was 61.4 years, and 18.6% of cases included involvement of more than three organs. The prevalence of brain, liver, and bone metastases was 22.2%, 25.1%, and 32.3%, respectively. Patients without liver metastases derived significantly greater survival benefit from chemoimmunotherapy than from chemotherapy alone (PFS: 8.9 vs. 6.6 months; OS: 21.8 vs. 12.9 months); in contrast, despite a numerical increase, patients with liver metastases showed no significant improvement from chemoimmunotherapy in PFS (6.4 vs. 4.8 months) or OS (10.8 vs. 9.5 months). Multivariate analysis identified liver metastases as an independent prognostic factor among patients treated with chemoimmunotherapy for worse PFS [hazard ratio (HR) =2.71, 95% confidence interval (CI): 1.62-4.51] and OS (HR =2.64, 95% CI: 1.49-4.70). The meta-analysis confirmed that while immunotherapy benefited both groups, the HRs of OS were consistently higher in patients with liver metastases. CONCLUSIONS: The presence of liver metastases is a critical prognostic factor for outcomes in patients with ES-SCLC. These patients derive limited benefit from the current standard of care, underscoring the urgent need for novel therapeutic strategies to improve the prognosis of this subgroup.