Murray Nigel P, Fuentealba Cynthia, Reyes Eduardo, Jacob Omar
Hospital Carabineros de Chile. Nunoa. Santiago. Chile. Facultad de Medicina. Universidad Finis Terrae. Providencia. Santiago. Chile.
Hospital Carabineros de Chile. Nunoa. Santiago. Chile.
Arch Esp Urol. 2017 Jun;70(5):503-512.
The limitations of total serum PSA values remains problematic; nomograms may improve the prediction of a positive prostate biopsy (PB). We compare in a prospective study of Chilean men with suspicion of prostate cancer due to an elevated total serum PSA and/or abnormal digital rectal examination, the use of two on-line nomograms with the detection of primary malignant circulating prostate cells (CPCs) to predict a positive PB for high risk prostate cancer.
Consecutive men with suspicion of prostate cancer underwent 12 core TRUS prostate biopsy. Age, total serum PSA and percent free PSA, family history, ethnic origin and prostate ultrasound results were registered. Risk assessment was performed using the online nomograms. The European Randomized Study of Screening for Prostate Cancer derived Prostate Risk Indicator (SWOP-PRI) and the North American Prostate Cancer Prevention Trail derived Prostate Risk Indicator (PCPT-CRC) were used to calculate risk of prostate cancer. Immediately before PB an 8 ml blood sample was taken to detect CPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunomarcation with anti-PSA and anti- P504S. Biopsies were classified as cancer/no-cancer, CPC detection test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for total serum PSA, free percent, PSA, SWOP-PRI, PCPT-CRC and CPCs were calculated and compared. Diagnostic yields were calculated, including the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed.
1,223 men aged 〉 55 years were analyzed, 467 (38.2%) had a biopsy positive for cancer of which 114/467 (24.45) complied with the criteria for active observation; 177/467 (36.8%) were Gleason 7 or higher. Discriminative power of detecting prostate cancer, showed areas under the curve of total PSA 0.559, SWOP nomogram 0.687, PCPTRC nomogram 0.716, free percent PSA 0.765 and CPC detection 0.844. CPC detection was superior to the other models (p〈0.0001). Using the recommended cutoff values, free percent PSA avoided 81% of biopsies missing 58% of significant cancers; for the other models the values were SWOP 75% and 56%; PCPTRC 61% and 62%, CPC detection 57% and 4% respectively.
CPC detection was superior to the other models in predicting the presence of clinically significant prostate cancer at initial biopsy; potentially reduces the number of unnecessary biopsy while missing few significant cancers. Being a positive/negative test it avoids defining a cutoff value which may differ between populations. Multicenter studies to validate this method are warrented.
总血清前列腺特异抗原（PSA）值存在局限性，这一问题仍然很棘手；列线图可能会改善前列腺穿刺活检（PB）阳性的预测。在一项针对因总血清PSA升高和/或直肠指检异常而怀疑患有前列腺癌的智利男性的前瞻性研究中，我们比较了两种在线列线图与原发性恶性循环前列腺细胞（CPCs）检测在预测高危前列腺癌PB阳性方面的应用。
连续纳入怀疑患有前列腺癌的男性，进行12针经直肠超声引导下前列腺穿刺活检。记录年龄、总血清PSA和游离PSA百分比、家族史、种族起源以及前列腺超声检查结果。使用在线列线图进行风险评估。采用欧洲前列腺癌筛查随机研究得出的前列腺风险指标（SWOP - PRI）和北美前列腺癌预防试验得出的前列腺风险指标（PCPT - CRC）来计算前列腺癌风险。在PB前即刻采集8ml血液样本以检测CPCs。通过差异凝胶离心法获取单核细胞，并使用抗PSA和抗P504S双重免疫标记进行鉴定。将活检结果分为癌/非癌，CPC检测结果分为阴性/阳性，并记录每8ml中的细胞总数。计算并比较总血清PSA、游离PSA百分比、PSA、SWOP - PRI、PCPT - CRC和CPCs的曲线下面积（AUC）。计算诊断率，包括可避免的可能穿刺活检数量以及会漏诊的临床显著癌症数量。
对122名年龄大于55岁的男性进行了分析，其中467名（38.2%）穿刺活检结果为癌症阳性，其中114/467（24.4%）符合主动观察标准；177/467（36.8%）的 Gleason评分≥7分。检测前列腺癌的鉴别能力方面，总PSA的曲线下面积为0.559，SWOP列线图为0.687，PCPT - CRC列线图为0.716，游离PSA百分比为0.765，CPC检测为0.844。CPC检测优于其他模型（p＜0.0001））。使用推荐的临界值，游离PSA百分比可避免81%的穿刺活检，漏诊58%的显著癌症；其他模型的相应数值分别为SWOP列线图75%和56%；PCPT - CRC列线图61%和62%，CPC检测分别为57%和4%。
在预测初次活检时临床显著前列腺癌的存在方面，CPC检测优于其他模型；可能减少不必要的穿刺活检数量，同时漏诊的显著癌症数量很少。作为一项阳性/阴性检测，它避免了定义可能因人群而异的临界值。需要进行多中心研究来验证该方法。
