Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine

Br J Cancer. 2017 Aug 8;117(4):583-587. doi: 10.1038/bjc.2017.210. Epub 2017 Jul 6.

Abstract

Background: Urothelial bladder cancer (UBC) is characterised by a high risk of recurrence. Patient monitoring is currently based on iterative cystoscopy and on urine cytology with low sensitivity in non-muscle-invasive bladder cancer (NMIBC). Telomerase reverse transcriptase (TERT) is frequently reactivated in UBC by promoter mutations.

Methods: We studied whether detection of TERT mutation in urine could be a predictor of UBC recurrence and compared this to cytology/cystoscopy for patient follow-up. A total of 348 patients treated by transurethral bladder resection for UBC were included together with 167 control patients.

Results: Overall sensitivity was 80.5% and specificity 89.8%, and was not greatly impacted by inflammation or infection. TERT remaining positive after initial surgery was associated with residual carcinoma in situ. TERT in urine was a reliable and dynamic predictor of recurrence in NMIBC (P<0.0001). In univariate analysis, TERT positive-status after initial surgery increased risk of recurrence by 5.34-fold (P=0.0004). TERT positive-status was still associated with recurrence in the subset of patients with negative cystoscopy (P=0.034).

Conclusions: TERT mutations in urine might be helpful for early detection of recurrence in UBC, especially in NMIBC.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Carcinoma, Transitional Cell / urine*
  • Cystoscopy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / urine*
  • Neoplasm, Residual
  • Population Surveillance / methods*
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Prospective Studies
  • Telomerase / genetics
  • Telomerase / urine*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Urinary Bladder Neoplasms / urine*
  • Urine / cytology

Substances

  • TERT protein, human
  • Telomerase