Novel urinary biomarkers ADXBLADDER and bladder EpiCheck for diagnostics of bladder cancer: A review

Jur Robert Erica Wolfs, Tom Johannes Noël Hermans, Evert Louwerens Koldewijn, Daan van de Kerkhof (Corresponding author)

Research output: Contribution to journalReview articlepeer-review

16 Citations (Scopus)


Non-muscle-invasive bladder cancer (NMIBC) is accompanied with high incidence and recurrence rates. The extensive need for cystoscopic follow up causes substantial patient discomfort and leads to a high economic burden. Cytology of exfoliated tumor cells in urine is not able to safely reduce or replace the amount of cystoscopies. Here, we give a short overview of established urinary biomarkers and review 2 novel urinary biomarkers, ADXBLADDER and Bladder EpiCheck, for their clinical utility in NMIBC. A Pubmed literature search was performed on the subject of urinary biomarkers for NMIBC. The performance of urinary cytology and established biomarkers Nuclear matrix proteins (NMP22), BTA, UroVysion, and ImmunoCyt was evaluated. The performance of novel biomarkers ADXBLADDER and Bladder EpiCheck was critically reviewed. Based on available clinical studies, established urinary biomarkers have no clear role in the diagnosis or follow-up of NMIBC. Three available prospective studies of ADXBLADDER (2 studying initial diagnosis and 1 follow-up study) reported overall sensitivity (45%–73%) and negative predictive values (NPV) (74%–100%) superior to cytology, with reasonable specificity (70%–73%). Four follow-up Bladder EpiCheck studies reported overall sensitivity (62%–90%) and NPV (79%–97%) superior to cytology, with a high specificity (82%–88%). For detection of high grade recurrences, sensitivity, and NPV of both novel biomarkers were even higher, with a sensitivity and NPV of 76% to 88% and 99% respectively for ADXBLADDER and 79% to 95% and 99% respectively for Bladder EpiCheck – Novel urinary biomarkers ADXBLADDER and Bladder EpiCheck have better sensitivity and NPV, but worse specificity than cytology in the follow-up of NMIBC. In the future, these biomarkers might reduce the amount of follow-up cystoscopies, for instance via an intermittent follow-up scheme alternating between cystoscopy and biomarker testing. The main biomarker objective should be to rule out high grade tumor recurrence without the need for any invasive procedures. Nevertheless, the clinical implementation of these biomarkers in the follow up of NMIBC has to be further investigated in prospective randomized trials for low as well as high grade tumors.

Original languageEnglish
Pages (from-to)161-170
Number of pages10
JournalUrologic oncology
Issue number3
Early online date26 Dec 2020
Publication statusPublished - Mar 2021


  • Bladder EpiCheck
  • Follow-up
  • Nonmuscle invasive bladder cancer
  • Recurrence


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