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Improved Prognostic Stratification Using Circulating Tumor Cell Clusters in Patients with Metastatic

Chun Wang, Zhenchao Zhang, Weelic Chong, Rui Luo, Ronald E Myers, Jian Gu, Jianqing Lin, Qiang Wei, Bingshan Li, Timothy R Rebbeck, Grace Lu-Yao, William K Kelly, Hushan Yang

PMID: 33450815 PMCID: PMC7828213 DOI: 10.3390/cancers13020268


Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of CTC-clusters. In 227 longitudinally collected blood samples from 64 mCRPC patients, CTCs and CTC-clusters were enumerated using the CellSearch platform. The associations of CTC and CTC-cluster counts with progression-free survival (PFS) and overall survival (OS), individually and jointly, were evaluated by Cox models. CTCs and CTC-clusters were detected in 24 (37.5%) and 8 (12.5%) of 64 baseline samples, and in 119 (52.4%) and 27 (11.9%) of 227 longitudinal samples, respectively. CTC counts were associated with both PFS and OS, but CTC-clusters were only independently associated with an increased risk of death. Among patients with unfavorable CTCs (≥5), the presence of CTC-clusters signified a worse survival (log-rank p = 0.0185). mCRPC patients with both unfavorable CTCs and CTC-clusters had the highest risk for death (adjusted hazard ratio 19.84, p = 0.0072), as compared to those with <5 CTCs. Analyses using longitudinal data yielded similar results. In conclusion, CTC-clusters provided additional prognostic information for further stratifying death risk among patients with unfavorable CTCs.

Keywords: circulating tumor cell; circulating tumor cell cluster; metastatic castration-resistant prostate cancer; overall survival; progression-free survival.

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