Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer

Br J Cancer. 2022 Jul;127(2):329-336. doi: 10.1038/s41416-022-01785-8. Epub 2022 Mar 29.

Abstract

Background: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers.

Methods: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis.

Results: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-7-2.8 × 10-2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80).

Conclusions: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Biomarkers, Tumor / urine
  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / urine
  • Cross-Sectional Studies
  • Female
  • Hematuria
  • Humans
  • Male
  • Neoplasm Recurrence, Local
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / urine
  • Volatile Organic Compounds* / urine

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Volatile Organic Compounds