A Molecular Urine Assay to Detect Recurrences During Surveillance of High-Risk Non-Muscle Invasive Bladder Cancer.

Autor:	de Jong JJ; Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands., de Jong FC; Department of Urology, Erasmus MC Urothelial Cancer Research Group, Rotterdam, The Netherlands., van der Made ACJ; Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands., van Casteren NJ; Department of Urology, Franciscus Hospital, Rotterdam, The Netherlands., Roshani H; Department of Urology, Haga Teaching Hospital, The Hague, The Netherlands., Oomens EHGM; Department of Urology, Amphia Hospital, Breda, The Netherlands., Pelger RCM; Department of Urology, Leiden University Medical Center, Leiden, The Netherlands., Steyerberg EW; Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands., Boormans JL; Department of Urology, Erasmus MC Urothelial Cancer Research Group, Rotterdam, The Netherlands., Bangma CH; Department of Urology, Erasmus MC Urothelial Cancer Research Group, Rotterdam, The Netherlands., Zuiverloon TCM; Department of Urology, Erasmus MC Urothelial Cancer Research Group, Rotterdam, The Netherlands., Zwarthoff EC; Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Bladder cancer (Amsterdam, Netherlands) [Bladder Cancer] 2024 Oct 23; Vol. 10 (3), pp. 233-242. Date of Electronic Publication: 2024 Oct 23 (Print Publication: 2024).
DOI:	10.3233/BLC-240017
Abstrakt:	Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients require long-term surveillance with cystoscopies, cytology and upper tract imaging. Previously, we developed a genomic urine assay for surveillance of HR-NMIBC patients with high sensitivity and anticipatory value. Objective: We aimed to validate the performance of the assay in an unselected prospectively collected cohort of HR-NMIBC patients under surveillance. Methods: We included patients from five centers and collected urine sample pairs (evening and morning urines) prior to cystoscopy. Mutation status ( FGFR3/TERT) and methylation status ( OTX1) was analyzed on DNA from voided urine specimens. A test was considered positive if≥1 alteration was detected in at least one urine sample. The primary endpoint was tumor recurrence. Sensitivity and specificity were determined. A generalized mixed effects model was used to adjust for within-patient correlation. Cox proportional hazard analyses with time-dependent covariates assessed the anticipatory effect of the urine assay. Results: In total, 204 patients and 736 sample pairs were collected. Sixty-three recurrences were diagnosed for which we had concomitant assay results. On cross-sectional analyses, the assay detected 75% (95% CI 62.1% -84.7%) of recurrences, with a specificity of 70% (95% CI 66.4% -73.5%). Furthermore, mixed effects model analyses revealed OTX1 ( p  = 0.005) and TERT ( p  = 0.004) as significant predictors for disease recurrence. Median follow-up was 25.3 months (IQR 18.6-30.7). Twenty-nine tumors were diagnosed without concomitant urine samples, which included recurrences detected after urine collection ended. Longitudinal analyses showed that a positive urine assay predicted a recurrence over time (HR 3.5, p  < 0.001). Furthermore, a recurrence during the study period was also a predictor for developing future recurrences (HR 2.1, p < 0.001). Conclusions: This study validates the performance of a previously developed urine assay in an unselected cohort of HR-NMIBC patients under surveillance. With a robust sensitivity/specificity and a strong anticipatory effect, this assay proves a useful adjunct ready for evaluation in a future randomized controlled trial. Competing Interests: TZ and EZ are Editorial Board members of this journal, but were not involved in the peer-review process nor had access to any information regarding its peer-review. TZ declares Grant/Research support from: Genecentric/Janssen, InnoSign and Merk AG (all paid to Erasmus MC). EZ declares a License agreement with MDxHealth / Vesica and a patent for OTX1 and ONECUT2 methylation issued in EU and Canada, and a pending patent in the USA. JB declares consultantcy / speaker’s fee (all paid to Erasmus MC) from: Janssen, BMS, AstraZeneca, Merck AG/Pfizer, MSD, Bayer, Ismar Healtcare. Research collaborations with: Merck AG, MSD, Janssen, VitroScan and Merk Serono. Member of the Scientific Congress Committee European Association of Urology. JJ, FJ, AM, NC, HR, EO, RP, EW and CB declare no conflicts of interest related to this topic nor to the contents of this manuscript. (© 2024 – The authors. Published by IOS Press.)
Databáze:	MEDLINE
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