Relationship between tumor markers and overall survival in small cell lung cancer: a retrospective cohort study.

BACKGROUND: Some studies have investigated the prognostic value of tumor markers in small-cell lung cancer (SCLC), but results have been inconsistent, and the confounding effects across these markers remain unknown. The prognostic value of tumor markers in the era of immune, anti-angiogenesis, and targeted therapies has been less studied. This study aimed to analyze the relationship between serum tumor markers and overall survival (OS) in patients with treatment-naive SCLC. METHODS: We retrospectively collected clinical data from untreated SCLC patients and those with less missing information who visited Tianjin Medical University General Hospital between June 2019 and October 2022. Serum concentrations of four tumor markers, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), a fragment of cytokeratin 19 (CYFRA 21-1), and pro-gastrin-releasing peptide (proGRP), which were measured by electrochemiluminescence assay, were extracted from their medical records. Missing data were imputed using the MICE package. OS information was obtained via telephone follow-up. Survival curve, Cox proportional hazards model, restricted cubic spline (RCS), and time-dependent receiver operating characteristic (ROC) curve were used to analyze the relationship between tumor markers and patients' OS. RESULTS: A total of 160 patients were included in the study. CEA was positively correlated with CYFRA21-1, and proGRP was positively correlated with NSE and CYFRA21-1. In the multivariate Cox proportional hazards model, only CYFRA21-1 was independently associated with OS after adjusting for stage. RCS analysis showed a linear relationship between tumor markers and OS, with a hazard ratio (HR) around 1.5 at high marker concentrations. Time-dependent ROC curves showed that the area under the curve (AUC) for tumor markers in predicting OS was around 0.6. CONCLUSIONS: CEA, NSE, proGRP, and CYFRA21-1 are linearly associated with OS in patients with SCLC. Among the four investigated tumor markers, CYFRA21-1 shows the strongest association.