Urine-based biomarkers for the early detection and surveillance of non-muscle invasive bladder cancer

Minerva Urol Nefrol. 2008 Dec;60(4):217-35.

Abstract

Bladder cancer has a very high frequency of recurrence and therefore requires lifelong surveillance, traditionally consisting of serial cystoscopy and cytology. These tests are both invasive and expensive, with considerable inter-user and inter-institutional variability. In addition, the sensitivity of cytology in detecting low-grade tumors is low. Therefore, there has been active investigation into urinary biomarkers that can either supplement or supplant these tests. At this point there are only six urine-based tests that are FDA-approved in bladder cancer surveillance, but a wide variety of other biomarkers are being studied. In this review, we examine the natural history of bladder cancer as well as the rationale and performance of an ideal urinary biomarker. The authors describe the FDA-approved biomarkers such as Bladder Tumor Antigen, ImmunoCyt, Nuclear Matrix Protein-22, and Fluorescent In Situ Hybridization, as well as the most promising investigational tests (i.e., Urinary bladder cancer test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, and telomerase). The biological foundation, methodologies, and diagnostic performance of the biomarkers are discussed. The characteristics of the biomarkers are compared to urine cytology. At this time, urine biomarkers are utilized in a variety of clinical situations but their role is not well defined. The goal of identifying an optimal marker that will replace cystoscopy and/or cytology is still ongoing.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / urine
  • Biomarkers, Tumor / urine*
  • Carcinoma, Transitional Cell / diagnosis
  • Carcinoma, Transitional Cell / urine*
  • Cysteine Proteinase Inhibitors / urine
  • Cystoscopy
  • Fas Ligand Protein / urine
  • Humans
  • Hyaluronic Acid / urine
  • Hyaluronoglucosaminidase / urine
  • In Situ Hybridization, Fluorescence
  • Inhibitor of Apoptosis Proteins
  • Lewis X Antigen / urine
  • Microtubule-Associated Proteins / urine
  • Nuclear Proteins / urine
  • Population Surveillance / methods*
  • Prognosis
  • Sensitivity and Specificity
  • Survivin
  • Telomerase / urine
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / urine*

Substances

  • Adjuvants, Immunologic
  • BIRC5 protein, human
  • BLCA-4 protein, human
  • Biomarkers, Tumor
  • Cysteine Proteinase Inhibitors
  • Fas Ligand Protein
  • Inhibitor of Apoptosis Proteins
  • Lewis X Antigen
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Survivin
  • nuclear matrix protein 22
  • Hyaluronic Acid
  • Telomerase
  • Hyaluronoglucosaminidase