Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, India.
Guy's, King's and St. Thomas' Hospital, London, UK.
Cancer Med. 2023 Apr;12(8):9116-9127. doi: 10.1002/cam4.5649. Epub 2023 Jan 30.
The low specificity of serum PSA resulting in the inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. The low sensitivity of serum PSA results in false negatives and can miss high-grade prostate cancers. We describe a non-invasive test for detection of prostate cancer based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD-CTCs) from blood samples followed by their identification by immunostaining for pan-cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl-acyl coenzyme-A racemase (AMACR), epithelial cell adhesion molecule (EpCAM), and common leucocyte antigen (CD45).
Analytical validation studies were performed to establish the performance characteristics of the test using VCaP prostate cancer cells spiked into healthy donor blood (HDB). The clinical performance characteristics of the test were evaluated in a case-control study with 160 known prostate cancer cases and 800 healthy males, followed by a prospective clinical study of 210 suspected cases of prostate cancer.
Analytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study.
The test accurately detects PrAD-CTCs with high sensitivity and specificity irrespective of stage, serum PSA or Gleason score, which translates into low risks of false negatives or overdiagnosis. The high accuracy of the test could offer advantages over PSA based prostate cancer detection.
血清 PSA 的特异性低，导致无法有效地将前列腺癌与良性前列腺疾病区分开来，这是一个持续存在的临床挑战。血清 PSA 的灵敏度低导致假阴性，并可能错过高级别的前列腺癌。我们描述了一种基于从血液样本中富集前列腺腺癌相关循环肿瘤细胞（PrAD-CTCs），然后通过免疫染色鉴定 pan-cytokeratins（PanCK）、前列腺特异性膜抗原（PSMA）、α-甲基酰基辅酶 A 消旋酶（AMACR）、上皮细胞黏附分子（EpCAM）和普通白细胞抗原（CD45）来检测前列腺癌的非侵入性检测方法。
使用 VCaP 前列腺癌细胞掺入健康供体血液（HDB）进行分析验证研究，以确定该检测的性能特征。在一项包含 160 例已知前列腺癌病例和 800 例健康男性的病例对照研究中评估了该检测的临床性能特征，随后对 210 例疑似前列腺癌病例进行了前瞻性临床研究。
分析验证确定了分析物的稳定性和可接受的性能特征。该检测在病例对照研究中对区分前列腺癌病例和健康个体的特异性和敏感性均为 100%，在前瞻性临床研究中对区分前列腺癌和良性前列腺疾病的敏感性和特异性均为 91.2%和 100%。
该检测能够准确检测 PrAD-CTCs，具有高灵敏度和特异性，与疾病分期、血清 PSA 或 Gleason 评分无关，从而降低了假阴性或过度诊断的风险。该检测的高准确性可能优于基于 PSA 的前列腺癌检测。
