Combined measurement of circulating tumor cell counts and serum tumor marker levels enhances the screening efficiency for malignant versus benign pulmonary nodules

Thorac Cancer. 2022 Dec;13(23):3393-3401. doi: 10.1111/1759-7714.14702. Epub 2022 Oct 25.

Abstract

Background: The high false-positive rate for pulmonary nodules (PNs) from using low-dose computed tomography (LDCT) screening can lead to overuse of invasive procedures, overtreatment, and patient anxiety. Therefore, it is very important to develop new diagnostic methods.

Methods: A negative enrichment-fluorescence in situ hybridization (NE-FISH) approach was used to detect circulating tumor cells (CTCs) in patients with PNs. We evaluated whether or not the combination of CTC counts with serum tumor marker levels (CEA, CA 125, CYFRA 21-1, SCC) could improve the diagnostic ability for distinguishing patients with malignant pulmonary nodules (MPNs) from those with benign pulmonary nodules (BPNs). Moreover, the potential clinical application of this combination for the diagnosis of solitary pulmonary nodules (SPNs) with a diameter ≤2 cm was also investigated.

Results: The combination of CTC counts and tumor marker levels had a sensitivity of 80.12% and the area under the receiver operating characteristics curve (AUCROC ) of 0.853 (95% confidence interval [CI]: 0.800-0.897, p < 0.001) for the differential diagnosis of PNs. For early cancer stages, the sensitivity was 75.38% (AUCROC = 0.780, 95% CI: 0.713-0.838, p < 0.001). In addition, for SPNs within 2 cm the combination of CTC counts and tumor marker levels was still the most valuable diagnostic tool with a sensitivity of 78.95% and AUCROC of 0.888.

Conclusion: The combination of CTC counts and serum tumor marker levels is helpful for improving the diagnosis of PNs, especially in the early stages of cancer and for SPNs within 2 cm.

Keywords: circulating tumor cells; diagnosis; early stages; pulmonary nodules; tumor markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms* / pathology
  • Multiple Pulmonary Nodules*
  • Neoplastic Cells, Circulating* / pathology
  • Solitary Pulmonary Nodule* / diagnostic imaging

Substances

  • antigen CYFRA21.1
  • Biomarkers, Tumor