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

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.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).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.Bladder cancer is an important cause of morbidity and mortality with an estimated 386,300 new cases and 150,200 deaths occurring worldwide in 2008 alone [1]. The highest bladder cancer incidence rates are reported in Europe, North America, and Northern Africa and the majority of cases occur in men [1,2]. Urothelial (transitional cell) carcinomas are the most common histological type of bladder cancer. Non-urothelial vesical tumors are extremely rare and account for < 5% of all primary bladder malignancies combined [3]. Approximately 95% of primary urothelial cell cancers arise from the bladder and only a few cases originate from other sites within the urinary tract such as the renal pelvis and ureter [4-6].The most widely used system for bladder cancer staging at this time is the American Joint Committee on Cancer (AJCC) tumor, lymph node, and hematogenous metastasis (TNM) system [7]. According to this system, extravesical disease is categorized as either stage II