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

Abstract

PurposeTo 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.MethodsA 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.ResultsCTCs 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.ConclusionCTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.

Metabolic Profiling of Bladder Cancer Patients’ Serum Reveals Their Sensitivity to Neoadjuvant Chemotherapy

“…Liquid biopsy has been widely explored in recent years because of its convenience and low invasiveness. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) have great potential in predicting the efficacy of NAC in MIBC patients [11,12], and our previous study also confirmed the value of CTCs in predicting NAC sensitivity [13].…”

Advances in the Biology, Detection Techniques, and Clinical Applications of Circulating Tumor Cells

“…Based on the SE-iFISH strategy, Yang et al demonstrated that patients with early bladder cancer had more triploid CTCs, tetraploid CTCs, and total circulation endothelial cells (CECs). Various CTC/ CEC subtypes may have di erent potential function to guide the diagnosis, prognosis prediction, and treatment decision of bladder cancer [92]. Li et al found that the presence of circulating tumor-cell-associated white blood cell (CTC-WBC) clusters is an independent prognostic factor for advanced non-small-cell lung cancer [93].…”

Tumour microenvironment as a predictive factor for immunotherapy in non-muscle-invasive bladder cancer

“…The density of lymphatic vessels corelated with higher pT stage, higher grade and sessile growth patterns. It has been also detected that circulating endothelial cells (CECs) is associated with higher tumour stage and grade [ 104 ].…”