Rational: Circulating tumor cells (CTCs) appear to be a promising tool for predicting the clinical outcome and monitoring the response to treatment in patients with solid tumors. The current study assessed the clinical relevance of monitoring CTCs in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel. Patients and Methods: Patients with histologically confirmed mCRPC who were previously treated with a docetaxel-containing regimen and experienced disease progression were enrolled in this multicenter prospective study. CTC counts were enumerated using the CellSearch system at baseline (before cabazitaxel initiation), after one cabazitaxel cycle (post 1st cycle) and at disease progression (PD). Patients were stratified into predetermined CTC-positive and CTC-negative groups. The phenotypic characterization was performed using double immunofluorescence staining with anti-CKs and anti-Ki67, anti-M30 or anti-vimentin antibodies. Results: The median PFS and OS were 4.0 (range, 1.0–17.9) and 14.5 (range, 1.2–33.9) months, respectively. At baseline, 48 out of 57 (84.2%) patients had ≥1 CTCs/7.5 mL of peripheral blood (PB) and 37 (64.9%) had ≥5 CTCs/7.5 mL of PB. After one treatment cycle, 30 (75%) out of the 40 patients with available measurements had ≥1 detectable CTC/7.5 mL of PB and 24 (60%) ≥ 5CTCs/7.5 mL of PB; 12.5% of the patients with detectable CTCs at the baseline sample had no detectable CTCs after one treatment cycle. The detection of ≥5CTCs/7.5 mL of PB at baseline and post-cycle 1 was associated with shorter PFS and OS (p= 0.002), whereas a positive CTC status post-cycle 1 strongly correlated with poorer OS irrespective of the CTC cut-off used. Multivariate analysis revealed that the detection of non-apoptotic (CK+/M30−) CTCs at baseline is an independent predictor of shorter OS (p= 0.005). Conclusions: In patients with mCRPC treated with cabazitaxel, CTC counts both at baseline and after the first cycle retain their prognostic significance, implying that liquid biopsy monitoring might serve as a valuable tool for predicting treatment efficacy and survival outcomes.
背景：循环肿瘤细胞（CTCs）在预测实体瘤患者临床结局及监测治疗反应方面展现出潜在应用价值。本研究评估了卡巴他赛治疗的转移性去势抵抗性前列腺癌（mCRPC）患者中CTC监测的临床相关性。 患者与方法：这项多中心前瞻性研究纳入了经组织学确诊、既往接受过多西他赛方案治疗且出现疾病进展的mCRPC患者。采用CellSearch系统分别在基线期（卡巴他赛治疗前）、第一周期治疗后及疾病进展时进行CTC计数。根据预设阈值将患者分为CTC阳性组与阴性组。通过抗细胞角蛋白（CK）分别与抗Ki67、抗M30或抗波形蛋白抗体的双重免疫荧光染色进行表型特征分析。 结果：患者中位无进展生存期（PFS）为4.0个月（范围：1.0-17.9），中位总生存期（OS）为14.5个月（范围：1.2-33.9）。基线期57例患者中48例（84.2%）外周血CTC≥1个/7.5 mL，37例（64.9%）≥5个/7.5 mL。第一周期治疗后，40例可评估患者中30例（75%）CTC≥1个/7.5 mL，24例（60%）≥5个/7.5 mL；基线期可检测到CTC的患者中，12.5%在第一周期治疗后未检测到CTC。基线期及第一周期治疗后CTC≥5个/7.5 mL与较短的PFS和OS显著相关（p=0.002），而第一周期治疗后CTC阳性状态（无论采用何种阈值）均与较差的OS密切相关。多变量分析显示，基线期非凋亡性（CK+/M30-）CTC是OS缩短的独立预测因子（p=0.005）。 结论：在卡巴他赛治疗的mCRPC患者中，基线期及第一周期治疗后的CTC计数均具有预后价值，提示液体活检监测可能成为预测治疗效果和生存结局的重要工具。
肿瘤(癌症)患者之家