Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTC_M score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTC_L score predicts microscopic dissemination to seminal vesicles and/or lymph nodes (P < 0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer.

Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288–303. ©2018 AACR.

See related commentary by Heitzer and Speicher, p. 269.

This article is highlighted in the In This Issue feature, p. 253

基于血液的生物标志物在转移性前列腺癌中至关重要，在转移性前列腺癌中，特征性骨转移瘤不易取样，它们可能使局部疾病的风险分层。我们建立了灵敏且高通量的策略，使用微流控细胞富集，然后对前列腺衍生的转录物进行数字化定量分析前列腺循环肿瘤细胞（CTC）。在一项针对一线阿比特龙治疗的27例转移性去势抵抗性前列腺癌患者的前瞻性研究中，数字CTC _M评分的治疗前升高表明高危人群的总生存期较差（HR = 6.0; P = 0.01），且生存期短影像学无进展生存期（HR = 3.2；P = 0.046）。表达HOXB13CTCs中的s识别出6例≤12个月生存率的患者中的6例，其中一部分还表达了ARV7剪接变体。在34名患有局限性前列腺癌的男性的第二个队列中，术前CTC _L评分升高预示着微观扩散到精囊和/或淋巴结（P <0.001）。因此，对CTC特异性转录本进行数字化定量分析可以进行无创监测，从而可以指导转移性和局限性前列腺癌的治疗选择。

重要性：迫切需要生物标志物来指导前列腺癌的治疗，局部癌的治愈性治疗以及分子靶向药物在转移性疾病中的应用。血液样本中前列腺CTC来源的转录物的数字化定量预测了转移性癌症中阿比特龙的反应以及局部性癌症中的早期传播。巨蟹座Discov; 8（3）；288–303。©2018 AACR。

参见Heitzer和Speicher的相关评论，第1页。269。

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