CTCs in Patients with Lung Cancer Associated with a Poor Prognosis

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Lung cancer remains the leading cause of cancer-related mortality worldwide. Even with recent surgical and medical advances, most cases are inoperable due to functional reasons or because the cancer has metastasized. Complications from metastatic disease contribute to 44% of lung cancer deaths. Another 37% of deaths are from indirect complications from malignant disease. Direct complications from the primary tumor contribute to only 12% of deaths from lung cancer.

Circulating tumor cells (CTCs) are shed by the primary tumor or by metastatic tumors into the blood stream and lend a poor prognosis to patients. Detection of CTCs in the blood stream is complicated, and attempts to identify and isolate CTCs from other blood cells have proven difficult due to the heterogeneity of CTCs. Though currently there is no consensus on physical traits or surface markers to universally identify and isolate CTCs, CTCs could potentially offer a means to prognosticate and predict response to therapy. However, studies that include CTCs only focus on subpopulations, and the prognostic value of CTCs is unclear in lung cancer.

In an attempt to assess the prognostic value of CTCs in the different histological types of lung cancer, a comprehensive meta-analysis of clinical data with respect to CTC subtypes, cutoffs, and time points of CTC enumeration was performed. In total, 27 studies enrolling 2957 participants were identified and analyzed. CTC detection was found to be prognostic for both poor overall survival and progression-free survival. Subgroup analysis according to histological subtype found statistically significant influences on the prognostic value of CTCs. In patients with small-cell lung cancer, CTC detection indicated a poorer prognosis and predicted a worse outcome compared with patients with non–small-cell lung cancer.

Mesenchymal and epithelial markers are used in CTC studies. Epithelial-mesenchymal transition hybrids have been demonstrated to be drivers of metastasis in malignancy. A subgroup analysis of 21 studies was conducted to determine whether different markers would modify the prognostic value for overall survival. This analysis found that epithelial CTCs predicted a worse patient outcome than epithelial-mesenchymal hybrids or mesenchymal CTCs.

The studies used different cutoffs to define CTC positivity. In order to determine if this could contribute to heterogeneity, a subgroup analysis was performed and found that cutoffs significantly modified the prognostic value of CTCs for overall survival. If the cutoff was set at 1 CTC per 7.5 mL, the hazard ratio was underestimated, with the underestimation no longer present when the cutoff was ≥2 CTCs per 7.5 mL.

Pretreatment and posttreatment analysis and stratification of surgical versus nonsurgical treatment found no significant subgroup effect in the prognostic value of CTCs.

Source: Jin F, Zhu L, Shao J, et al. Circulating tumour cells in patients with lung cancer universally indicate poor prognosis. Eur Respir Rev. 2022;31(166):220151.

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