TY - JOUR
T1 - Improved prognostic stratification using circulating tumor cell clusters in patients with metastatic castration-resistant prostate cancer
AU - Wang, Chun
AU - Zhang, Zhenchao
AU - Chong, Weelic
AU - Luo, Rui
AU - Myers, Ronald E.
AU - Gu, Jian
AU - Lin, Jianqing
AU - Wei, Qiang
AU - Li, Bingshan
AU - Rebbeck, Timothy R.
AU - Lu-Yao, Grace
AU - Kelly, William K.
AU - Yang, Hushan
N1 - Publisher Copyright:
© 2021 by the authors.
PY - 2021/1/2
Y1 - 2021/1/2
N2 - 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.
AB - 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.
KW - Circulating tumor cell
KW - Circulating tumor cell cluster
KW - Metastatic castration-resistant prostate cancer
KW - Overall survival
KW - Progression-free survival
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U2 - 10.3390/cancers13020268
DO - 10.3390/cancers13020268
M3 - Article
C2 - 33450815
AN - SCOPUS:85099556090
SN - 2072-6694
VL - 13
SP - 1
EP - 13
JO - Cancers
JF - Cancers
IS - 2
M1 - 268
ER -