Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity

Xiao Yang; Jiancheng Lv; Zijian Zhou; Dexiang Feng; Rui Zhou; Baorui Yuan; Qikai Wu; Hao Yu; Jie Han; Qiang Cao; Min Gu; Pengchao Li; Haiwei Yang; Qiang Lu

doi:10.3389/fonc.2021.802188

Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity

Front Oncol. 2022 Feb 3:11:802188. doi: 10.3389/fonc.2021.802188. eCollection 2021.

Authors

Xiao Yang¹, Jiancheng Lv¹, Zijian Zhou¹, Dexiang Feng¹, Rui Zhou^{1

2}, Baorui Yuan¹, Qikai Wu¹, Hao Yu¹, Jie Han¹, Qiang Cao¹, Min Gu¹, Pengchao Li¹, Haiwei Yang¹, Qiang Lu¹

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Abstract

Purpose: To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer.

Methods: A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan-Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity.

Results: CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance.

Conclusion: CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.

Keywords: bladder cancer; circulating endothelial cells; circulating tumor cells; neoadjuvant chemosensitivity; prognosis.