Association between antibiotic exposure and outcomes of chemoimmunotherapy in extensive-stage small cell lung cancer: a single-center retrospective cohort study

Background: Lung cancer remains a leading cause of cancer incidence and mortality worldwide. Small cell lung cancer (SCLC), though only 15% of cases, shows aggressive biological behavior and poor prognosis. Chemoimmunotherapy is the standard first-line treatment for extensive-stage SCLC (ES-SCLC). Gut microbiota affects immunotherapy in other cancers, but its role in ES-SCLC is unclear. This study examined the association of antibiotics, cathartics, and probiotics with the efficacy of chemoimmunotherapy in ES-SCLC.

Methods: This retrospective study enrolled patients with ES-SCLC receiving chemoimmunotherapy at the Guangdong Lung Cancer Institute (GLCI). Kaplan-Meier curves and Cox regression were used to evaluate associations of antibiotic, cathartic, and probiotic use with progression-free survival (PFS) and overall survival (OS). Multivariable Cox regression models, including an Akaike information criterion (AIC)-based model and a clinically guided model with prespecified covariates, were used to evaluate the association between antibiotic exposure and survival outcomes. Propensity score-based weighting and matching, together with additional sensitivity analyses, were performed to assess the robustness of antibiotic-related associations.

Results: Antibiotic exposure was associated with shorter PFS in univariable Cox regression [hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.41–5.22; P=0.003] and multivariable Cox regression (AIC model: HR: 2.63, 95% CI: 1.28–5.41; P=0.008; clinical model: HR: 2.16, 95% CI: 1.06–4.39; P=0.03). Antibiotic exposure was also associated with shorter OS in univariable analysis (HR: 6.02, 95% CI: 3.06–11.84; P<0.001) and multivariable analysis (AIC model: HR: 6.88, 95% CI: 3.26–14.54; P<0.001; clinical model: HR: 5.34, 95% CI: 2.62–10.87; P<0.001). Propensity score-weighted and sensitivity analyses showed generally consistent directions of association, whereas propensity score-matched analyses showed a consistent adverse direction without reaching statistical significance. Cathartic and probiotic use were not significantly associated with PFS or OS in exploratory analyses.

Conclusions: Antibiotic exposure was associated with shorter PFS in ES-SCLC patients receiving chemoimmunotherapy, with generally consistent findings across multiple analyses. The OS association was also observed. However, these results should be interpreted cautiously given the small exposed cohort, residual confounding, and possible proportional hazards violations. Prospective multicenter validation with detailed antibiotic, infection, and microbiome data is warranted.