Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Translational Cancer Research Unit (TCRU), GZA Hospitals Sint-Augustinus, Antwerp, Belgium.
Prostate Cancer Prostatic Dis. 2021 Jun;24(2):499-506. doi: 10.1038/s41391-020-00304-1. Epub 2020 Nov 23.
Although most patients with metastatic castration-resistant prostate cancer (mCRPC) initially benefit from treatment with androgen receptor signaling inhibitors (ARSi), resistance inevitably occurs. Hence, we investigated the prognostic value of automated circulating tumor cell (CTC) and tumor-derived extracellular vesicle (tdEV) enumeration and their dynamics, in patients with mCRPC in the context of the initiation of treatment with ARSi. Furthermore, we hypothesize that CTC phenotypic heterogeneity might serve as a measurable biomarker under these circumstances.
Using an image analysis tool, we reanalyzed all CellSearch images previously acquired in the context of a prospective, multicenter clinical study for patients with mCRPC (n = 170) starting a new line of ARSi, for CTC and tdEV detection and enumeration. CTC (n = 19 129) phenotypic diversity was quantified by the Shannon index (SI). Progression-free survival (PFS) and overall survival (OS) were compared between groups of patients stratified according to CTC, tdEV, and SI levels.
Automated CTC enumeration provided similar clinical prognostication compared with operator-based counts. Patients demonstrating high CTC phenotypic heterogeneity before therapy had a shorter median PFS (4.82 vs. 8.49 months, HR 1.79; P = 0.03) and OS (12.6 months vs. not reached, HR 2.32; P = 0.03), compared to patients with low diversity, irrespective of CTC level. Multivariable analysis showed how the prognostic value of the baseline SI was lost by pretreatment chemotherapy status, CTC counts, and PSA levels.
Automated CTC counts are a reliable substitute for reviewer-based enumeration, as they are equally informative for prognosis assessment in patients with mCRPC. Beyond enumeration, we demonstrated the added value of studying CTC phenotypic diversity for patient prognostication, warranting future investigation.
尽管大多数转移性去势抵抗性前列腺癌（mCRPC）患者最初受益于雄激素受体信号抑制剂（ARSi）的治疗，但不可避免地会产生耐药性。因此，我们研究了在开始使用 ARSi 治疗的情况下，自动化循环肿瘤细胞（CTC）和肿瘤衍生细胞外囊泡（tdEV）计数及其动态变化对 mCRPC 患者的预后价值。此外，我们假设在这种情况下，CTC 表型异质性可以作为一种可测量的生物标志物。
我们使用图像分析工具，重新分析了在一项前瞻性、多中心临床研究中，为接受新一线 ARSi 治疗的 mCRPC 患者（n=170）检测和计数 CTC 和 tdEV 时之前获取的所有 CellSearch 图像。通过香农指数（SI）量化 CTC（n=19129）表型多样性。根据 CTC、tdEV 和 SI 水平对患者进行分层，比较各组患者的无进展生存期（PFS）和总生存期（OS）。
与基于操作人员的计数相比，自动化 CTC 计数提供了相似的临床预后。与低多样性患者相比，治疗前具有高 CTC 表型异质性的患者的中位 PFS（4.82 与 8.49 个月，HR 1.79；P=0.03）和 OS（12.6 个月与未达到，HR 2.32；P=0.03）均较短，而不论 CTC 水平如何。多变量分析表明，预处理化疗状态、CTC 计数和 PSA 水平如何使基线 SI 的预后价值丧失。
自动化 CTC 计数是基于观察者计数的可靠替代品，因为它们同样为 mCRPC 患者的预后评估提供信息。除了计数之外，我们还证明了研究 CTC 表型异质性对患者预后的附加价值，值得进一步研究。
