Lokeshwar V B, Soloway M S
Department of Urology, University of Miami School of Medicine, Miami, Florida, USA.
J Urol. 2001 Apr;165(4):1067-77.
We reviewed currently available bladder cancer tests in the context of the clinical expectations of a noninvasive bladder cancer test.
We reviewed the literature on bladder cancer tests that are commercially available or have shown clinical usefulness and examined how each test compares with standard methods of bladder cancer diagnosis.
The clinical necessity for a noninvasive test for bladder cancer is 2-fold, including the early detection of high grade bladder tumors before muscle invasion and monitoring tumor recurrence or new onset. An ideal noninvasive test should be sensitive, specific, rapid, technically simple and have low intra-assay and interassay variability. Urine cytology has high specificity but limited applicability due to its relatively low sensitivity and subjective nature. Hematuria detection by Hemastix dipstick is sensitive but not specific for detecting bladder cancer. Molecules associated with bladder tumor growth and progression may serve as a basis for designing noninvasive diagnostic tests. The Food and Drug Administration approved BTA Stat and BTA TRAK tests, which detect human complement factor H and a related protein in urine, have 60% to 80% sensitivity and 50% to 70% specificity (lower in symptomatic patients) for bladder cancer. The Food and Drug Administration approved NMP22 test, which measures the level of nuclear mitotic apparatus protein in urine, has 50% to 100% sensitivity and 60% to 90% specificity. Accu-Dx detects fibrin degradation products, fibrin and fibrinogen in urine, although this test is no longer commercially available. The Immunocyt test combines cytology with an immunofluorescence technique to improve the sensitivity of cytology for detecting low grade tumors. The telomeric repeat amplification protocol assay for telomerase in exfoliated cells has 70% to 86% sensitivity and 60% to 90% specificity for bladder cancer. However, the low stability of telomerase in urine affects its sensitivity. The hyaluronic acid and hyaluronidase (HA-HAase) test, which measures the urinary level of hyaluronic acid and hyaluronidase, has 90% to 92% sensitivity and 80% to 84% specificity for bladder cancer. Quanticyt karyometry evaluates nuclear shape and DNA content of exfoliated cells to detect bladder cancer. The list of bladder tumor markers is growing rapidly and large multicenter trials are essential to assess their usefulness.
Although currently noninvasive bladder cancer tests cannot replace cystoscopy, some have shown a promise of being clinically useful. One or a combination of these tests-markers may prove to be a prostate specific antigen for bladder cancer provided that patients and, more importantly, clinicians accept it.
我们在无创膀胱癌检测的临床预期背景下，回顾了目前可用的膀胱癌检测方法。
我们回顾了关于市售或已显示出临床实用性的膀胱癌检测方法的文献，并研究了每种检测方法与膀胱癌诊断标准方法的比较情况。
对膀胱癌进行无创检测的临床必要性有两方面，包括在肌肉浸润前早期检测高级别膀胱肿瘤以及监测肿瘤复发或新发情况。理想的无创检测应具备敏感性高、特异性强、快速、技术操作简单以及批内和批间变异低等特点。尿细胞学检查特异性高，但由于其相对较低的敏感性和主观性，适用性有限。Hemastix试纸条检测血尿对膀胱癌敏感但不具有特异性。与膀胱肿瘤生长和进展相关的分子可作为设计无创诊断检测方法的基础。美国食品药品监督管理局批准的BTA Stat和BTA TRAK检测，可检测尿液中的人补体因子H和一种相关蛋白，但对膀胱癌的敏感性为60%至80%，特异性为50%至70%（有症状患者中较低）。美国食品药品监督管理局批准的NMP22检测，用于测量尿液中核有丝分裂器蛋白水平，其对膀胱癌的敏感性为50%至100%，特异性为60%至90%。Accu-Dx检测尿液中的纤维蛋白降解产物、纤维蛋白和纤维蛋白原，不过该检测已不再商业化供应。免疫细胞检测将细胞学与免疫荧光技术相结合，以提高细胞学检测低级别肿瘤的敏感性。脱落细胞中端粒酶的端粒重复扩增协议检测对膀胱癌的敏感性为70%至86%，特异性为60%至90%。然而，端粒酶在尿液中的稳定性较低影响了其敏感性。透明质酸和透明质酸酶（HA-HAase）检测，用于测量尿液中透明质酸和透明质酸酶的水平，对膀胱癌的敏感性为90%至92%，特异性为80%至84%。定量细胞形态测量法评估脱落细胞的核形态和DNA含量以检测膀胱癌。膀胱癌标志物的清单正在迅速增加，大型多中心试验对于评估它们的实用性至关重要。
尽管目前无创膀胱癌检测方法不能替代膀胱镜检查，但其中一些已显示出临床应用的前景。如果患者以及更重要的是临床医生能够接受，这些检测方法或标志物中的一种或组合可能会成为膀胱癌的前列腺特异性抗原。
