FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study

J Urol. 2017 Jun;197(6):1410-1418. doi: 10.1016/j.juro.2016.12.096. Epub 2016 Dec 31.

Abstract

Purpose: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.

Materials and methods: In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.

Results: Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p <0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.

Conclusions: Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.

Keywords: cystoscopy; local; neoplasm recurrence; neoplasm invasiveness; urinalysis; urinary bladder neoplasms.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / urine*
  • Cystoscopy
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / urine*
  • Otx Transcription Factors / urine*
  • Population Surveillance
  • Predictive Value of Tests
  • Prospective Studies
  • Receptor, Fibroblast Growth Factor, Type 3 / urine*
  • Telomerase / urine*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*

Substances

  • Biomarkers, Tumor
  • OTX1 protein, human
  • Otx Transcription Factors
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3
  • TERT protein, human
  • Telomerase