Selected diagnostic tests for BCa
| Name | Material | Technology | Biomarker | Pros and cons | References |
|---|---|---|---|---|---|
| Cytology | Urine | Giemsa and H&E staining | Cell phenotype | Urine cytology, used in conjunction with cystoscopy, is the classic noninvasive diagnostic test for BCa. It is easy to perform, inexpensive, and can achieve a specificity of up to 98% in detecting high-grade tumors. However, its sensitivity (SN) is low (less than 40%), which limits its usefulness as a stand-alone diagnostic tool. | [64] |
| NMP22 | Urine | ELISA | Peptide | In the case of NMP22 detection tests in patients with microscopic hematuria (three or more red blood cells in the field of view), the NMP22 test showed higher SN (70%) compared with cytology alone (27%). The SN of this test depends on the stage of the tumor, being lower in detecting low-grade lesions. The presence of NMP22 in normal urothelial cells can lead to false positive results, which reduces the specificity of the test to 80%. | [65] |
| UroVysion | Urine | RYBA | DNA | UroVysion is a test that identifies common chromosomal abnormalities associated with BCa, including changes in chromosomes 3, 7, and 17, and the most common deletion 9p21. The test is expensive and requires specialized equipment and trained personnel. A comparative study showed that UroVysion had higher SN (62% compared to urine cytology) but lower specificity. It is recommended that UroVysion be used only in high-risk patients, especially in cases where urine cytology is equivocal. | [66, 67] |
| BTA | Urine | Immuno-analysis using a test strip | Protein | The BTA test, approved for monitoring patients with NMIBCa, is rapid and does not require special urine preparation, making it a convenient tool. Studies have shown that BTA Stat has a higher SN than cytology (56%), although a lower specificity (85.7%). In a group of 194 patients with BCa and 185 controls, the SN increased to 73.6%, and the specificity was 83.3%. However, this test tends to produce false positive results in cases of inflammation and previous BCG instillations, which reduces its specificity. | [68, 69] |
| UroSEEK | Urine | Massively parallel sequencing study | DNA | The UroSEEK test, based on next-generation sequencing (NGS) technology, detects ten mutations typical of BCa, such as FGFR3, TP53, ERBB2, CDKN2A and alterations in the TERTp region by Sanger sequencing. Its main role is to complement cytological diagnostics, rather than replace it. It shows higher SN than cytology, achieving better results in the monitoring (71%) and primary detection (95%) groups. It is also worth noting that the test has lower SN in detecting minimal amounts of mutations, which may limit its accuracy in such cases. | [70] |
| EpiCheck | Urine | Real-time PCR | DNA | EpiCheck, the only test on the market, uses 15 urinary DNA methylation markers to detect BCa recurrence. The EpiScore algorithm rates the probability of cancer on a scale of 0 to 100. In a study of 353 patients with NMIBCa, EpiCheck showed a SN of 68.2%, specificity of 88.0%, and negative predictive value (NPV) of 95.1%. After excluding low-grade recurrences, its AUC was 0.94, suggesting that it is effective in monitoring high-risk patients. EpiCheck is superior to cytology in SN (62.3%), although it is less specific (86.3%). Additionally, inflammation does not affect the results, which is undoubtedly a great advantage, although the test is expensive and requires specialist handling. | [71, 72] |
| CxBladder | Urine | RT-qPCR | RNA | CxBladder is a test that uses five RNA markers (CDC2, HOXA13, MDK, IGFBP5, CXCR2) and analyzes their expression using PCR. The algorithms (CxBladder-D and CxBladder-S) assess the risk of cancer and its recurrence. In studies, it has shown greater SN (over 80%) than cytology and NMP22 tests, with a specificity of 85%. CxBladder can also distinguish between low- and high-risk cancers, allowing for better management of patient priorities in the diagnosis and monitoring of BCa. | [73] |
| Xpert Detection | Urine | RT-qPCR | RNA | Xpert Bladder Cancer Detection is a rapid and noninvasive urine test that detects BCa by analyzing the expression of five mRNA markers (ABL1, ANXA10, UPK1B, CRH, IGF2) using the automated GeneXpert system and RT-PCR technology. The test has a high SN of 78%, especially in high-grade tumors, where SN is 90%, and a high NPV of 98%. Compared to cytology and UroVysion, Xpert offers better results in terms of detecting BCa, making it an effective tool to exclude the disease in patients with hematuria and low risk of BCa. | [74] |
| Uromonitor | Urine | Real-time PCR | DNA | Uromonitor is a test for detecting mutations in the TERTp and FGFR3 genes in the DNA of cancer cells present in urine, based on real-time PCR technology. The urine filtration system allows for pre-processing and preservation of the sample. In the validation study, Uromonitor achieved 73.5% SN and 73.2% specificity in detecting BCa recurrence, which was similar to the results of cystoscopy. Uromonitor-V2, which adds detection of mutations in the KRAS gene, achieved 100% SN and 83.3% specificity in the group of patients with NMIBCa, making it an effective tool for monitoring BCa. | [33, 75] |
BCa: bladder cancer; BTA: bladder tumor antigen; FGFR3: fibroblast growth factor receptor 3; NMP22: nuclear matrix protein 22; MIBCa: muscle-invasive BCa; NMIBCa: non-muscle invasive BCa
