Preoperative evaluation of solitary pulmonary nodules and adenocarcinoma invasiveness using ultra-high-resolution computed tomography and multidimensional liquid biopsy: a prospective exploratory study.

Background: Accurate preoperative characterization of solitary pulmonary nodules (SPNs), particularly differentiation of benign from malignant lesions and assessment of adenocarcinoma invasiveness, remains challenging based on morphological features alone. We investigated whether integrating 1024-matrix ultra-high-resolution computed tomography (UHRCT) with two liquid-biopsy signals, urinary cellular energy metabolism (CEM) and a seven tumor-associated autoantibody (7-TAAb) panel, could improve diagnostic performance in surgically treated patients with SPNs. Methods: In this single-center prospective study, consecutive adults with SPNs (≤3 cm) scheduled for video-assisted thoracoscopic surgery between January 2022 and December 2024 were enrolled (n = 183). All patients underwent preoperative UHRCT (1024×1024), urinary CEM testing, and 7-TAAb testing. A paired subgroup (n = 85) additionally underwent conventional HRCT (512×512) within 1 month before surgery. Postoperative histopathology served as the reference standard. Diagnostic performance metrics were calculated for each modality, parallel-rule combined strategies, and probability-based logistic regression models. Results: Among 183 patients, 164 (89.6%) had malignant nodules. UHRCT achieved the best single-modality discrimination (AUC, 0.831; sensitivity, 87.2%; specificity, 78.9%), outperforming CEM (AUC, 0.605) and 7-TAAbs (AUC, 0.558). Under the parallel-rule strategy, multimodal testing increased sensitivity but markedly reduced specificity (sensitivity 98.8%, specificity 9.5%). The probability-based fully integrated model achieved the highest AUC (0.946). At the Youden-index threshold of 0.816, this model yielded sensitivity of 92.7%, specificity of 84.2%, PPV of 98.1%, NPV of 57.1%, and accuracy of 91.8%. In the paired comparison (n = 85), UHRCT showed higher sensitivity (92.0% vs. 68.0%) and specificity (90.0% vs. 73.3%) than HRCT. For invasiveness assessment, positivity rates of both urinary CEM (57.6% vs. 31.6%) and 7-TAAbs (53.8% vs. 31.0%) were higher in invasive adenocarcinoma than in pre-invasive lesions. Conclusion: In surgically selected patients with SPNs, 1024-matrix UHRCT provided the strongest single-modality diagnostic information, while urinary CEM and 7-TAAbs offered complementary biological signals associated with invasive adenocarcinoma pathology. Probability-based integration provided a more balanced diagnostic framework than a simple parallel-rule strategy. Given the high prevalence of malignancy and the limited number of benign lesions, these findings should be considered exploratory and require external validation in broader outpatient and screening cohorts.