Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

Abstract

Background: The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease.

Methods: Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated.

Results: Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26).

Conclusions: CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests.

Figure 1

Study flowchart of selection of eligible studies included in the meta-analyses computations.

Figure 2

Diagnostic accuracy forest plots. Forest plots of the overall sensitivity (A), specificity (B), positive likelihood ratio (LR+) (C), and negative likelihood ratio (LR-) (D) of circulating tumor cell detection are presented. The size of each square is proportional to sample size. Horizontal lines in each square show the corresponding 95% confidence intervals (CI). The center of the diamond indicates the overall sensitivity, specificity, LR+, and LR- and the ends correspond to 95%CI.

Figure 3

Forest plots of association of circulating tumor cell (CTC) detection with disease stage. Forest plots of overall association of CTC detection with disease stage were calculated by pooling data from all assays in eligible studies (A) and by pooling data from a single detection assay per study (B). The size of each square is proportional to sample size. The center of each square and the horizontal line show the odds ratio (OR) and corresponding 95% confidence intervals (CI), respectively. The center of the diamond indicates overall OR and the ends correspond to 95%CI.

Figure 4

Sensitivity analyses. One-way sensitivity analysis of pooled data from all assays in the 12 eligible studies (A) and from a single marker assay from each of the 12 eligible studies (B). Each rectangle represents pooled odds ratio (OR); horizontal lines show corresponding 95% confidence intervals (CI) after omitting each study.