Salami Simpa S, Singhal Udit, Spratt Daniel E, Palapattu Ganesh S, Hollenbeck Brent K, Schonhoft Joseph D, Graf Ryon, Louw Jessica, Jendrisak Adam, Dugan Lyndsey, Wang Yipeng, Tomlins Scott A, Dittamore Ryan, Feng Felix Y, Morgan Todd M
Michigan Medicine, Ann Arbor, MI.
University of Michigan Rogel Cancer Center, Ann Arbor, MI.
JCO Precis Oncol. 2019;3. doi: 10.1200/po.18.00352. Epub 2019 May 30.
Using nonenrichment-based, potentially more sensitive Epic Sciences circulating tumor cell (CTC) platform, we sought to detect and characterize CTCs in untreated, high-risk localized prostate cancer and to evaluate their clinical implication.
Between 2012 and 2015, blood samples were prospectively collected from patients with National Comprehensive Cancer Network high-risk localized prostate cancer undergoing either radiotherapy (XRT) plus androgen deprivation therapy or radical prostatectomy (RP) with curative intent. Samples were analyzed with the Epic Sciences platform with 4,6-diamidino-2-phenylindole, CD45, cytokeratin (CK), and androgen receptor (AR) -terminal staining. CTC counts were correlated with biochemical recurrence (BCR).
A diversity of CTC subtypes, including CK-positive, CK-negative, AR-positive, and CTC clusters, were observed in 73.3% (33 of 45) of patients with evaluable data. The median follow-up was 14.2 months (range, 0.5 to 43.7 months). BCR occurred more frequently in the RP group than XRT (15 of 26 one of 19), with most patients in the XRT group continuing to receive androgen deprivation therapy. A higher proportion of metastatic events were observed in the RP group (five of 26 one of 19). In the RP group, BCR and development of metastases were associated with a higher total number of CTCs, AR-positive CTCs, and CTC phenotypic heterogeneity. One patient who developed BCR and metastases quickly after RP had diverse phenotypical CTC subtypes, and single-cell genomic analyses of all detectable CTCs confirmed common prostate cancer copy number alterations and loss.
CTCs can be identified in most patients with high-risk localized prostate cancer before definitive therapy using the Epic Sciences platform. If confirmed in a larger cohort with longer follow-up, phenotypic and genomic characterization of CTCs pretherapy may provide an additional means of risk stratifying patients with newly diagnosed high-risk disease and potentially help identify patients who could require multimodal therapy.
使用基于非富集的、可能更敏感的Epic Sciences循环肿瘤细胞（CTC）平台，我们试图检测和表征未经治疗的高危局限性前列腺癌中的CTC，并评估其临床意义。
2012年至2015年期间，前瞻性地收集了患有美国国立综合癌症网络高危局限性前列腺癌且接受放疗（XRT）加雄激素剥夺治疗或根治性前列腺切除术（RP）且有治愈意图的患者的血样。使用Epic Sciences平台对样本进行4,6-二脒基-2-苯基吲哚、CD45、细胞角蛋白（CK）和雄激素受体（AR）末端染色分析。CTC计数与生化复发（BCR）相关。
在73.3%（45例中的33例）有可评估数据的患者中观察到多种CTC亚型，包括CK阳性、CK阴性、AR阳性和CTC簇。中位随访时间为14.2个月（范围为0.5至43.7个月）。BCR在RP组中比XRT组更频繁发生（26例中的15例对19例中的1例），XRT组中的大多数患者继续接受雄激素剥夺治疗。在RP组中观察到更高比例的转移事件（26例中的5例对19例中的1例）。在RP组中，BCR和转移的发生与更高的总CTC数量、AR阳性CTC以及CTC表型异质性相关。1例在RP后迅速发生BCR和转移的患者具有多种表型的CTC亚型，对所有可检测到CTC的单细胞基因组分析证实了常见的前列腺癌拷贝数改变和缺失。
使用Epic Sciences平台可以在大多数高危局限性前列腺癌患者接受确定性治疗之前识别出CTC。如果在更大队列且更长随访时间内得到证实，治疗前CTC的表型和基因组表征可能为新诊断的高危疾病患者提供额外的风险分层手段，并可能有助于识别可能需要多模式治疗的患者。
