一项前瞻性研究方案，评估循环肿瘤细胞状态以预测局限性前列腺癌患者根治性前列腺切除术治疗失败的风险（C-ProMeta-1）。
Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1).
机构信息
Dept. of Urology, University College London Hospitals, London, UK.
Queen Mary University of London, Barts Cancer Institute, London, UK.
出版信息
BMC Cancer. 2023 Jun 23;23(1):581. doi: 10.1186/s12885-023-11081-0.
BACKGROUND
Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence.
METHODS
We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time.
DISCUSSION
CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment.
TRIAL REGISTRATION
ISRCTN17332543.
背景
前列腺癌 (PCa) 的治疗决策依赖于局限性和转移性阶段的疾病分层，但目前的成像分期技术对微转移疾病不敏感。循环肿瘤细胞 (CTC) 状态是这方面很有前途的工具。Parsortix® CTC 分离系统采用基于细胞大小和变形性的独立于表位的方法，以提高 CTC 的捕获率。在这里，我们提出了一项前瞻性评估该方法的方案，以预测根治性前列腺切除术后 (RP) PCa 癌症复发。
方法
我们计划招募 294 名被诊断为不利的中、高和极高危局限性 PCa 的患者。排除标准包括同时诊断出癌症或之前接受过 PCa 治疗，包括激素治疗。RP 按照标准护理进行。在 RP 前和 RP 后 3 个月采集两次血液样本（20 ml）。临床团队对 CTC 结果不知情，实验室研究人员对临床信息不知情。治疗失败定义为 PSA≥0.2mg/ml、开始挽救治疗或影像学证实有转移病灶。CTC 分析包括对捕获的 CTC 进行计数和 RNA 分析以检测基因表达。主要结局是 CTC 状态预测 4.5 年后 RP 后治疗失败的准确性。将报告观察到的敏感性、阳性和阴性预测值。特异性将随时间呈现。
讨论
CTC 状态可能反映了 PCa 转移的真实潜力，并且可能比当前的 PCa 进展风险分级系统更好地预测临床结局。因此，建立一种强大的生物标志物来预测局限性高危 PCa 的治疗失败将显著增强治疗决策的指导，优化治愈率，同时最大限度地减少过度治疗的不必要伤害。
试验注册
ISRCTN83304649。
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