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The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma: a meta-analysis of 30 published studies.

ABSTRACT: There are inconsistent conclusions in the association between circulating tumor cells (CTCs) and urothelial cancer (UC). We performed a meta-analysis to assess the prognostic and diagnostic value of CTCs in UC. We search Medline, Embase and Web of science for relevant studies. The study was set up according to the inclusion/exclusion criteria. 30 published studies with a total of 2161 urothelial cancer patients were included. Meta-analysis showed that CTC-positive was significantly associated with tumor stage (? II vs III, IV) (OR = 4.60, 95% CI: 2.34-9.03), histological grade (I, II vs III) (OR = 2.91, 95% CI: 1.92-4.40), metastasis (OR = 5.12, 95% CI: 3.47-7.55) and regional lymph node metastasis (OR = 2.47, 95% CI: 1.75-3.49). It was also significantly associated with poor overall survival (OS) (HR = 3.98, 95% CI: 2.20-7.21), progression/disease-free survival (PFS/DFS) (HR = 2.22, 95% CI: 1.80-2.73) and cancer-specific survival (CSS) (HR = 5.18, 95% CI: 2.21-12.13). Overall sensitivity and specificity of CTC detection assays were 0.35 (95% CI: 0.28-0.43) and 0.97 (95% CI: 0.92-0.99) respectively. In summary, our meta-analysis suggests that the presence of CTCs in the peripheral blood is an independent predictive indicator of poor outcomes for urothelial cancer patients. It can also be used as a noninvasive method for the confirmation of cancer diagnosis. More studies are required to further explore the role of this marker in clinical practice.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5601752 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma: a meta-analysis of 30 published studies.

Zhang Zheng Z Fan Wei W Deng Qiaoling Q Tang Shihui S Wang Ping P Xu Peipei P Wang June J Yu Mingxia M

Oncotarget 20170616 35

There are inconsistent conclusions in the association between circulating tumor cells (CTCs) and urothelial cancer (UC). We performed a meta-analysis to assess the prognostic and diagnostic value of CTCs in UC. We search Medline, Embase and Web of science for relevant studies. The study was set up according to the inclusion/exclusion criteria. 30 published studies with a total of 2161 urothelial cancer patients were included. Meta-analysis showed that CTC-positive was significantly associated wi ...[more]

PMID: 28938656

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Project description:Objectives:The aim of this study was to investigate the prognostic effect of amplified in AIB1 and EIF5A2 expression on postoperative intravesical recurrence for upper urinary tract urothelial carcinoma (UTUC) and improve postoperative risk stratification and prediction of intravesical chemotherapy benefit. Materials and methods:We evaluated immunohistochemical expression of AIB1 and EIF5A2 in 109 UTUC patients to determine the predictive significance in intravesical recurrence. A prognostic model was developed based on univariate and multivariate analyses. Results:Intravesical recurrence occurred in 18 out of the 109 (16.5%) patients during the follow-up period. Significant associations of high expression of AIB1 and EIF5A2 with shortened bladder recurrence interval (median: 24 months vs 46 months, P=0.021; 28 months vs 39 months, P=0.002) were demonstrated. In different subsets of UTUC patients, high expression of AIB1 was a prognostic indicator in high grade (P=0.006) and pT2-4 (P=0.007), and high expression of EIF5A2 for high grade (P=0.014), pT2-4 (P=0.002) and pN0 (P=0.009). Moreover, in multivariate analysis, AIB1 and EIF5A2 expression (P=0.034 and 0.022, respectively) together with pN stage (P=0.009) provided significant independent predictors for intravesical recurrence after surgery for UTUC. Surgical approach with radical nephroureterectomy (RNU) was an informative factor toward good oncologic outcomes for intravesical recurrence (P=0.056). Based on a prognostic model with these factors, patients with UTUC were classified into the low-risk group and the high-risk group. In a subset analysis, the patients in the high-risk group were found to have a favorable response to intravesical chemotherapy (P=0.047). A nomogram based on the multivariate analysis was developed to predict intravesical recurrence accurately and guide postoperative intravesical instillations. The concordance index (c-index) of this model was 0.806. Conclusion:High expression of AIB1 and EIF5A2 were independent predictors for intravesical recurrence after RNU and might be able to predict which patients benefit from postoperative intravesical chemotherapy.

Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

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The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma: a meta-analysis of 30 published studies.

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The prognostic and diagnostic value of circulating tumor cells in bladder cancer and upper tract urothelial carcinoma: a meta-analysis of 30 published studies.

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