Assessment of the Clinical Utility of Circulating Tumor Cells at Different Time Points in Predicting Prognosis of Patients With Small Cell Lung Cancer: A Meta-Analysis

Abstract

Objectives: Numerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC.

Methods: PubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg's and Egger's tests were also conducted.

Results: Sixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC.

Conclusion: Dynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.

Keywords: circulating tumor cells; meta-analysis; prognosis; small cell lung cancer.

Figure 1.

Flow chart of literature selection.

Figure 2.

Forest plots of the association between pretreatment CTCs status and prognosis in patients with SCLC. (A, B) the impact of higher pretreatment CTCs level detected by CellSearch (A) and other methods (B) and OS; (C, D) the impact of higher pretreatment CTCs level detected by CellSearch (C) and other methods (D) on PFS. CTCs, circulating tumor cells; SCLC, small cell lung cancer; OS, overall survival; PFS, progression-free survival.

Figure 3.

Forest plots of the association between post-therapy CTCs status and prognosis in patients with SCLC. (A, B) the impact of higher post-therapy CTCs level detected by CellSearch (A) and other methods (B) on OS; (C) the impact of higher post-therapy CTCs level detected by CellSearch on PFS. CTCs, circulating tumor cells; SCLC, small cell lung cancer; OS, overall survival; PFS, progression-free survival.

Figure 4.

Sensitivity analyses and funnel plots of the impact of higher pretreatment CTCs status detected by CellSearch on prognosis in patients with SCLC. (A, B) sensitivity analyses of the impact of higher pretreatment CTCs level detected by CellSearch on OS (A) and PFS (B); (C, D) funnel plots of the impact of higher pretreatment CTCs status detected by CellSearch on OS (C) and PFS (D). CTCs, circulating tumor cells; SCLC, small cell lung cancer; OS, overall survival; PFS, progression-free survival.