Development and Internal Validation of a Patient-Level Diagnostic Model Integrating Folate Receptor-Positive Circulating Tumor Cells and Peripheral CD8 Count for Malignant-Versus-Benign Pathology Discrimination in a Pathology-Enriched Pulmonary Nodule Cohort.

BACKGROUND

In pathology-enriched referred hospital cohorts, stable radiologic-pathologic linkage is often unavailable, so patient-level malignant pathology may be a more reliable endpoint than lesion-specific malignancy. We aimed to develop and internally validate a blood-based model for patient-level malignant-versus-benign pathology discrimination.

METHODS

We retrospectively reviewed 283 consecutive eligible source records from 22 February 2023 to 12 May 2025. After excluding unclassifiable pathology, lesions > 30 mm when verifiable, and obvious extrapulmonary primary tumors, we defined a strict primary cohort. A prespecified complete-case logistic regression model including FR + CTC, peripheral CD8 count, age, and sex was developed and internally validated with bootstrap resampling.

RESULTS

The strict primary cohort included 234 patients (166 malignant, 68 benign). In the main model (n = 232), FR + CTC was associated with higher odds of malignant pathology (OR 1.31 per 1 FU/3 mL, 95% CI: 1.14-1.50; p < 0.001), whereas peripheral CD8 count was inversely associated (OR 0.50 per 100 cells/μL, 95% CI: 0.41-0.61; p < 0.001). Apparent and optimism-corrected AUCs were 0.877 and 0.867, respectively. Adding an adjudicated patient-level CT vascular sign yielded limited incremental value.

CONCLUSION

In this retrospective single-center, pathology-enriched cohort, FR + CTC and peripheral CD8 provided useful internally validated discrimination for patient-level malignant pathology. The model requires external validation and setting-appropriate recalibration before broader clinical use.