Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification

Abstract

Purpose:Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors.Materials and Methods:Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect.Results:In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect–negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect–positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001).Conclusions:This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.

Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification. Letter.

“…To the Editor: We appreciate the interest in our manuscript. 1 We believe that we have thoroughly discussed the strengths and limitations of our own work in the publication, and we are happy to be given the further opportunity to discuss its limitations.…”

“…To the Editor: We read with interest the article by Lotan et al, reporting on enhanced Cxbladder tests that incorporate 5 mRNA biomarkers and DNA analysis of FGFR3 and TERT genes for the detection of urothelial carcinoma (UC). 1 This multicenter, prospective study included 804 patients with hematuria from the U.S. and Singapore, using midstream urine samples, and was retrospectively analyzed by enhanced Cxbladder. The results revealed better performance of Cxbladder diagnostic tests with the addition of DNA mutation analysis.…”

“…To the Editor: We read with great interest the study investigating the novel role of intravesical mitomycin-C (MMC) in nonmuscle-invasive bladder cancer (NMIBC) in a neoadjuvant setting. 1 Single, immediate, post-transurethral resection of bladder tumor (TURBT) instillation of MMC is the standard protocol in NMIBC. 2 It primarily reduces the recurrence risk by eliminating viable residual tumors and preventing reseeding of the free-floating cancer cells.…”

“…Patients requiring systemic therapy (metastases) will likely have significantly worse prognoses than those with cT1a RCC; however, our data set is underpowered to comment on outcomes of patients subsequently requiring extirpative surgery after AT (13 in the AT cohort and 18 in the PN cohort). 1,7 There are many strengths of our manuscript using the power of our national Canadian Kidney Cancer Information System database despite these limitations, and we appreciate its critical assessment and valuable comments by our colleagues. To the Editor: We read with interest the article by Lotan et al, reporting on enhanced Cxbladder tests that incorporate 5 mRNA biomarkers and DNA analysis of FGFR3 and TERT genes for the detection of urothelial carcinoma (UC).…”

Budgetary Impact of Including the Urinary Genomic Marker Cxbladder Detect in the Evaluation of Microhematuria Patients

“…Cxbladder Detect, a noninvasive genomic urinary biomarker test, has shown promise as a valuable diagnostic tool for improving the accuracy of bladder cancer diagnosis and reducing unnecessary diagnostic procedures. 3 Utilizing a proprietary algorithm based on 5 mRNA biomarkers, Cxbladder Detect provides a risk score to guide clinical decision-making regarding the need for cystoscopy in hematuria patients. 4 However, to implement Cxbladder Detect effectively into the diagnostic pathway, evaluating its budgetary and clinical implications is essential for supporting informed clinical decision-making and enhancing resource allocation in urology practices.…”