MP06-18: A Genomic Urine Assay to Detect Urinary Tract Recurrences in Patients with Bladder Cancer Treated with Radiotherapy

Florus C de Jong*, Iris I Iflé, Denise Kooper, Angelique CJ van der Made, Joep J De Jong, Tahlita CM Zuiverloon, Luca Incrocci, Rotterdam, Netherlands, Wim Van Criekinge, Gent, Belgium, Martine Franckena, Joost L Boormans, Ellen C Zwarthoff, Rotterdam, Netherlands

Introduction: Bladder-sparing radiotherapy is an alternative treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) who are unable or unwilling to undergo radical surgery. Follow-up consists of cystoscopy, urine cytology and imaging to detect recurrences. However, effects of radiotherapy hamper interpretation of cytology and cystoscopy. We investigated the diagnostic performance of a genomic urine assay to detect recurrences after (chemo-)radiation.

Methods: Patients with MIBC who underwent radiation from 2016-2020 were prospectively included. Follow-up consisted of cystoscopy (four/year) and upper tract imaging (twice/year). Prior to cystoscopy, an assay was performed to detect mutations in FGFR3, HRAS and TERT and methylation of OTX1, TWIST1 and ONECUT2. Primary endpoint was cross-sectional sensitivity, specificity and negative predictive value (NPV) that were associated with a previously developed logistic regression model for the detection of BC using this assay. Secondary endpoint was the risk of developing a recurrence during follow-up after a positive urine test, using a time-dependent Cox proportional hazard analysis.

Results: 143 patients were included and 503 urine tests were analyzed. The median follow-up time was 20 months (IQR 10–33), and the median time to a recurrence was 7 months (IQR 3–13). In 26/143 patients, 31 urinary tract recurrences were detected, including two upper tract tumors. 19/31 tumors had a concomitant urine test available. The diagnostic model had an area under the curve of 0.8 with a corresponding sensitivity, specificity and NPV of 77%, 78% and 99%. The test missed 4/19 tumors. When taking into account the anticipatory effect of the test (i.e. test can be positive prior to recurrence), 28/31 (91%) tumors were detected. A positive urine test was associated with a 13-fold higher risk of developing a future recurrence (p < 0.001).

Conclusions: We analyzed the diagnostic performance of a genomic urine assay to detect recurrences in MIBC patients treated with radiotherapy. The urine test was highly predictive of future recurrences and had a high NPV. If negative, the urine assay might be useful to replace cystoscopies. If positive, extra vigilance is warranted during surveillance. Further research is required to determine if the test is useful to develop a more adequate surveillance schedule.

Source of Funding: Erasmus MC Dept Pathology; MDx Health