Pleural effusion volume as a novel biomarker for prognostic and therapeutic stratification in small cell lung cancer: a translationally-focused cohort study.

BACKGROUND

Malignant pleural effusion (MPE) in small cell lung cancer (SCLC) is uniformly classified as extensive-stage disease. However, the prognostic heterogeneity based on effusion volume remains uncharacterized, leading to potential overtreatment of low-risk patients. This study aimed to define the distinct prognostic impact of effusion volume and identify survival determinants in the immunotherapy era.

METHODS

We analyzed 1,026 consecutive SCLC patients treated at Nanjing Jinling Hospital (2008-2024). MPE was cytologically confirmed. Effusion volume was radiographically categorized: small and moderate or greater pleural effusion (PE). The primary outcome was overall survival (OS). Multivariable Cox regression identified independent prognostic factors in the MPE cohort.

RESULTS

PE was present in 36.4% (373/1,026) of patients. Cytologically confirmed MPE via an indwelling catheter was identified in 75 patients (7.3%), all of whom had moderate or greater effusions. Strikingly, in the entire cohort stratified by radiographic volume, patients with small PEs had a median OS of 13.8 months, which was statistically indistinguishable from those with no effusion (14.8 months, P=0.54). Both groups fared significantly better than patients with moderate or greater PE (median OS 5.2 months, P<0.001). In the subgroup of cytologically confirmed MPE (n=75, all moderate or greater), multivariable analysis identified Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 [hazard ratio (HR) =4.64, 95% confidence interval (CI): 1.11-19.39, P=0.03], and elevated serum neuron-specific enolase (s-NSE >45.1 µg/L, HR =4.78, 95% CI: 1.14-19.97, P=0.03) as independent predictors of poor OS. Importantly, immunotherapy use was associated with a profound survival benefit (HR =0.18, 95% CI: 0.04-0.76, P=0.02).

CONCLUSIONS

MPE in SCLC is a prognostically heterogeneous condition. Effusion volume is a critical stratifier: small PE does not confer worse survival compared to no effusion, whereas moderate or greater PE is a strong independent predictor of poor outcome. Immunotherapy provides a significant survival benefit in MPE patients. These findings position radiographic effusion volume as a practical, clinically actionable biomarker.