Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer

Hege Marie Vedeld, Heidi Pharo, Anne Klara Sørbø, Sara Brandt-Winge, May Britt Five, Marine Jeanmougin, Per Guldberg, Rolf Wahlqvist, Guro Elisabeth Lind*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Cystoscopy is the gold standard for surveillance of non-muscle invasive bladder cancer (NMIBC), but the procedure is invasive and has suboptimal accuracy. The aim of this study was to investigate the potential of analyzing urine samples for the presence of urine tumor DNA (utDNA) to replace cystoscopy for surveillance of bladder cancer recurrence. In this longitudinal, prospective, and observational study, 47 patients were followed for recurrence for 2 years, involving analysis of utDNA using the BladMetrix DNA methylation biomarker test at each cystoscopy. In total, utDNA was detected in 21/23 recurrences (91% sensitivity), including 5/5 T1, T2, and carcinoma in situ (CIS) tumors (100%) and 10/12 Ta tumors (83%), with < 1% false-negative test results. Importantly, utDNA analysis showed the potential to reduce the number of cystoscopies by 55%, benefitting 79% of the patients. Eleven of 23 recurrences (48%) were detected earlier with utDNA than with cystoscopy, and distinct patterns of residual utDNA post-surgery indicated minimal residual disease (MRD) or field effect in 6% and 15% of the patients, respectively. In conclusion, utDNA analysis shows high sensitivity to detect tumor recurrence, potential to reduce the number of cystoscopies, and promise to guide patient-specific surveillance regimens.

Original languageEnglish
JournalMolecular Oncology
Volume18
Issue number11
Pages (from-to)2684-2695
ISSN1574-7891
DOIs
Publication statusPublished - Nov 2024

Keywords

  • biomarker
  • BladMetrix
  • DNA methylation
  • field effect
  • minimal residual disease
  • recurrence
  • Prospective Studies
  • Humans
  • Middle Aged
  • DNA, Neoplasm/urine
  • Cystoscopy
  • Male
  • DNA Methylation/genetics
  • Neoplasm Recurrence, Local/genetics
  • Urinary Bladder Neoplasms/urine
  • Aged, 80 and over
  • Female
  • Aged
  • Longitudinal Studies
  • Biomarkers, Tumor/urine

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