Ried Karin, Tamanna Tasnuva, Matthews Sonja, Eng Peter, Sali Avni
National Institute of Integrative Medicine (NIIM), Melbourne, VIC, Australia.
Department of Health, Torrens University, Melbourne, VIC, Australia.
Front Oncol. 2020 Apr 23;10:582. doi: 10.3389/fonc.2020.00582. eCollection 2020.
The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET®-CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET®-CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET®-CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer ( = 20). Secondary cancers were detected in 63% ( = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those ( = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% ( = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET®-CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level.
目前针对前列腺癌的筛查测试在全球10%的男性中进行，但其假阴性率高，真阳性率低。因此需要一种更可靠的筛查测试。循环肿瘤细胞（CTC）为早期致癌、癌症进展及治疗效果提供了一种生物标志物。基于细胞学的ISET®-CTC测试是一项经过临床验证的血液检测，具有高灵敏度和特异性。本研究旨在评估ISET®-CTC测试联合前列腺特异性标志物染色作为检测前列腺癌的筛查测试。我们从2014年9月至2019年7月正在进行的涉及2000例患者检测的CTC筛查研究中选取了47名男性，他们在CTC检测之前或之后也接受了标准的癌症诊断检测。在这47名男性中，有20名在ISET®-CTC测试之前被诊断为前列腺癌，另外27名男性接受了筛查。我们通过免疫细胞化学（ICC）检测，使用前列腺特异性标志物PSA，研究了45名CTC阳性男性中识别出的CTC。所有被诊断为原发性前列腺癌的男性（n = 20）的CTC均为ICC-PSA标志物阳性。在具有混合CTC群体（ICC-PSA阳性/ICC-PSA阴性）的男性中，63%（n = 7/11）检测到继发性癌症。在接受筛查的27名男性中，25名有CTC，其中84%（n = 20）的前列腺特异性PSA标志物呈阳性。后续检测显示，20/20名男性通过PSMA-PET扫描怀疑患有前列腺癌，45%（n = 9/20）的男性进行了活检，确诊为早期前列腺癌。在两名ICC-PSA标志物阴性的CTC男性中检测到肾癌或B细胞淋巴瘤。我们的研究表明，ISET®-CTC和ICC-PSA标志物检测相结合的估计阳性预测值（PPV）为99%，阴性预测值（NPV）为97%，与标准PSA血液检测（PPV = 25%；NPV = 15.5%）相比，为前列腺癌提供了更可靠的筛查测试。我们的研究结果值得进一步研究，以评估这种新测试在人群水平上进行前列腺癌筛查的潜力。
