Bladder Cancer: Test and Diagnosis

Laboratory parameters of 1st order – obligatory laboratory tests.

  • Urine status (rapid test for: pH, leukocytes, nitrite, protein, blood) [microhematuria: No visible discoloration of urine by blood; only erythrocytes/red blood cells are noticeable in the microscopic image (> 5 erythrocytes/μl urine); also perform erythrocyte morphology in case of microhematuria] In high-risk collectives (smokers, occupational risk groups), urine tests for microhematuria can detect bladder cancer earlier than in already symptomatic patients.
  • Urine cytology (spontaneous urine or flush cytology; fresh in urine or morning urine) – if malignant (malignant) change is suspectedNote:
    • Sensitivity (percentage of diseased patients in whom the disease is detected by use of the test, i.e., a positive test result occurs) is poor for low-grade NMIBC (non-muscle-invasive bladder cancer; non-muscle-invasive carcinoma of the urinary bladder) and moderate for high-grade tumors (undifferentiated or anaplastic malignant tissue). Therefore, it cannot be recommended in the early detection or screening of bladder cancer because of the excessive rate of false-negative findings. *
    • For the follow-up of high-grade tumors, cytology is particularly suitable because of the high specificity (probability that actually healthy people who do not have the disease in question, are also detected as healthy in the test).
    • In simultaneous cystitis or urolithiasis (urinary stone disease) cytology is complicated.
    • The procedure is highly examiner dependent.

* For low-grade carcinomas, urinary TERT analysis (detection of mutations in the telomerase reverse transcriptase (TERT) promoter) may be an appropriate procedure in the future to predict whether cancer cells will resprout after transurethral resection of bladder tissue (TUR-B). In one study, TERT analysis was able to predict in 80% of cases whether tumor cells would resprout during follow-up of at least six months. Further studies are awaited. 2nd-order laboratory parameters (for diagnosis, treatment planning, follow-up/therapy monitoring).

  • Fluorescence in situ hybridization (FISH, UroVysion), using gene probes to detect chromosomal abnormalities in urothelial cells: Aneuploidies of chromosomes 3, 7 and 17, and loss of heterocytogy (“loss of heterocygosity”, LOH) of 9p21; the procedure is independent of cytological changes due to benign diseases or therapy effects (e.g. after BCG therapy). Fluorescence in situ hybridization has a high sensitivity (74-100%) as well as a very high specificity (95-100%); FISH analysis thus allows a more reliable diagnosis than cytology.
  • Small blood count
  • Differential blood count
  • Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
  • Urine status: sediment, if necessary urine culture (pathogen detection and resistogram, that is, testing of suitable antibiotics for sensitivity / resistance).
  • Liver parameters – alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (gamma-GT, GGT), alkaline phosphatase, bilirubin.
  • Renal parameters – urea, creatinine, cystatin C or creatinine clearance, if necessary.
  • Alkaline phosphatase (AP) isoenzymes, ostase, urinary calcium (tumor hypercalcemia (synonym: tumor-induced hypercalcemia (calcium excess), TIH) is one of the most common symptoms in paraneoplastic syndromes), PTHrP (parathyroid hormone-related protein; the constellation with decreased parathyroid hormone (PTH) and increased PTHrP is typical for tumor hypercalcemia) – if bone metastases are suspected.
  • CYFRA 21-1 (cytokeratin 19 fragments) – tumor marker (diagnostic sensitivity in muscle-invasive bladder cancer: detectable up to 50% of cases).
  • Uro17TM (marker is the oncoprotein keratin 17 (K17)) – for recurrence diagnosis (sensitivity of 100% and a specificity of 96%).
  • Prognostic parameters in the diagnosis of non-muscle invasive and invasive urothelial carcinoma of the urinary bladder.
    • GATA3, p63, p40, CK20, CK5/6, S100P, uroplakin III – for detection of urothelial differentiation in metastases.
    • CK20, Ki-67, p53, CK5/6, and CD44 (at least three markers in parallel) – to differentiate reactive atypia of the urothelium from neoplastic changes (eg.B. dysplasia or carcinoma in situ).
  • PSA (prostate specific antigen) – due tohigh coincidence of prostate cancer in patients with condition n. radical cystectomy + increased risk of biochemical PSA recurrence; study duration: 10 years.

Recurrence diagnostics

  • Urine cytology (see above); Note: Negative cytology cannot reliably exclude low-grade carcinoim because the sensitivity is too poor.
  • Immunocytological or molecular genetic methods – to improve sensitivity (uCyt+) and specificity (see above: fluorescence in situ hybridization, FISH) in the low-grade range.
  • Uro17TM (marker is the oncoprotein keratin 17 (K17)) – for recurrence diagnosis (sensitivity of 100% and a specificity of 96%).

Screening for urinary bladder carcinoma

  • The use of commercially available blood and urine tests for early detection and screening for the presence of urinary bladder carcinoma outside of trials should not occur (EC).