Circulating Tumor and Endothelial Cells for Guiding Treatment in Patients with Bladder Cancer

By Patrick Daly - Last Updated: February 23, 2022

A study published in Frontiers in Oncology examined the value of circulating rare cells (CRCs)—particularly circulating tumor cells (CTCs) and circulating endothelial cells (CECs)—for aiding early intervention, guiding treatment decisions, and predicting prognosis in patients with bladder cancer. Reportedly, CTCs and CECs “may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer,” according to the study’s co-lead authors, Xiao Yang, Jiancheng Lv, Zijian Zhou, and Dexiang Feng.

The study enrolled a total of 196 patients with pathologically confirmed bladder cancer, with non-muscle invasive bladder cancer (NMIBC) in 141 and muscle invasive bladder cancer (MIBC) in 55. Thirty-two of the patients received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). The investigators assessed CTCs and CECs with a subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy. Additionally, overall survival (OS) and recurrence-free survival (RFS) were assessed with Kaplan-Meier analysis and Cox regression models.

The study’s authors found that triploid CTCs (p = 0.036), tetraploid CTCs (p = 0.019), and total CECs (p = 0.025) were higher in incipient patients than relapse patients. The number of total CECs and large cell CECs were associated with advanced tumor stage (p = 0.028 and p = 0.33) and grade (p = 0.028 and p = 0.041). Additionally, tumor-biomarker-positive CTCs were associated with worse OS (p = 0.026) and RFS (p = 0.038) in patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT), a finding which the authors described as “remarkable.” The investigation also found that CECs cluster was an independent predictor of recurrence in non-high-risk patients with NMIBC who underwent TURBT (hazard ratio [HR] = 9.21; p = 0.040).

Finally, the investigators reported that pre-NAC tetraploid CTCs and small cell CTCs “demonstrated the capability in discriminating NAC-sensitive from insensitive patients,” and that elevated post-NAC tetraploid CTCs and single CTCs was an indicator for resistance to chemotherapy. Taken together with their other CRC findings, the study’s collaborators ultimately concluded that “CTCs and CECs were related to clinicopathological characteristics,” and were entirely feasible for treatment guidance and prognosis prediction in patients with bladder cancer.