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Published on: January 5, 2017
A Urine-based Genomic Assay Improves Risk Stratification for Patients with High-risk Hematuria Stratified According
Joep J de Jong1, Olga M Pijpers1, Kim E M van Kessel1
1Department of Urology, Erasmus MC Urothelial Cancer Research Group, Rotterdam, The Netherlands.
Insights
A urine-based genomic assay significantly enhances the American Urological Association (AUA) risk stratification for urothelial carcinoma (UC) in hematuria patients. This test can help safely rule out cystoscopy for low-risk individuals and prioritize evaluation for high-risk patients.
Area of Science:
- Urology
- Genomics
- Oncology
Background:
- The American Urological Association (AUA) stratifies hematuria patients into low, intermediate, and high risk for urothelial carcinoma (UC) based on clinical factors.
- Current AUA guidelines do not incorporate urine-based tumor markers into risk stratification.
- Urothelial carcinoma (UC) risk stratification for hematuria patients is crucial for timely diagnosis and treatment.
Purpose of the Study:
- To determine if a urine-based genomic assay improves the AUA risk stratification for hematuria patients.
- To assess the diagnostic performance of a genomic assay in conjunction with AUA risk groups.
- To evaluate the impact of the genomic assay on post-test probabilities of UC.
Main Methods:
- A prospective Dutch hematuria cohort (n=838) with complete urinary DNA biomarker status was analyzed.
- Patients were stratified using AUA criteria (sex, age, hematuria type).
- Genomic biomarkers included gene mutation status (FGFR3, TERT, HRAS) and methylation status (OTX1, ONECUT2, TWIST1).
Main Results:
- The study included 65 low-risk (7.8%), 106 intermediate-risk (12.6%), and 667 high-risk (79.6%) patients.
- Urothelial carcinoma (UC) incidence was significantly higher in gross hematuria (21%) versus microscopic hematuria (4%).
- The genomic assay demonstrated robust performance (AUC 0.929-0.971) across risk groups, with negative tests yielding 0.3-2% post-test UC probability and positive tests yielding 31-42%.
Conclusions:
- A urine-based genomic assay adds significant value to AUA guideline stratification for hematuria.
- Negative urine assays may allow safe withholding of cystoscopy in AUA low-risk patients.
- Positive urine assays warrant expedited evaluation, particularly in AUA intermediate and high-risk groups.
Background:
According to the recent American Urological Association (AUA) guideline on hematuria, patients are stratified into groups with low, intermediate, and high risk of urothelial carcinoma (UC). These risk groups are based on clinical factors and do not incorporate urine-based tumor markers.
Objective:
To evaluate whether a urine-based genomic assay improves the redefined AUA risk stratification for hematuria.
Design, Setting, And Participants:
We selected patients with complete biomarker status, as assessed on urinary DNA, from a previously collected prospective Dutch hematuria cohort (n = 838). Patients were stratified into the AUA risk categories on the basis of sex, age, and type of hematuria. Biomarker status included mutation status for the FGFR3, TERT, and HRAS genes, and methylation status for the OTX1, ONECUT2, and TWIST1 genes.
Outcome Measurements And Statistical Analysis:
The primary endpoint was the diagnostic model performance for different hematuria risk groups. Further analyses assessed the pretest and post-test UC probability in the hematuria subgroups using a Fagan nomogram.
Results And Limitations:
Overall, 65 patients (7.8%) were classified as low risk, 106 (12.6%) as intermediate risk, and 667 (79.6%) as high risk. The UC incidence differed significantly between the gross hematuria (21%, 98/457) and microscopic hematuria (4%, 14/381) groups (p < 0.001). All cancer cases were in the high-risk group, which had UC incidence of 16.8% (112/667). Application of the diagnostic model revealed robust performance among all risk groups (area under the receiver operating characteristic curve 0.929-0.971). Depending on the risk group evaluated, a negative urine assay was associated with post-test UC probability of 0.3-2%, whereas a positive urine assay was associated with post-test UC probability of 31-42%.
Conclusions:
This study shows the value that a urine-based genomic assay adds to the AUA guideline stratification for patients with hematuria. It seems justified to safely withhold cystoscopy for patients with AUA low risk who have a negative urine assay. In addition, evaluation should be expedited for patients with AUA intermediate or high risk and a positive urine assay.
Patient Summary:
Patients who have blood in their urine (hematuria) can be classified as having low, intermediate, or high risk of having cancer in their urinary tract. We found that use of a urine-based genetic test improves the accuracy of predicting which patients are most likely to have cancer. Patients with a negative test may be able to avoid invasive tests, while further tests could be prioritized for patients with a positive test.
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