Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Abstract

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3

Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review

“…In a multicentric validation study, Uromonitor presented a sensitivity of 73.5% in the detection of TURB confirmed recurrence, with a specificity of 73.2% and overall good performance across stage and grade [56]. The values were comparable and similar to gold standard cystoscopy performance that presented values of 79.4% and 73.2% for sensitivity and specificity, respectively.…”

“…Uromonitor-V2 added Kirsten rat sarcoma viral oncogene homolog (KRAS) hotspot detection to the Uromonitor kit. The Uromonitor-V2 test presented in a multicenter study achieved 100% sensitivity, 83.3% specificity, a Positive Predictive Value (PPV) of 66.7% and a Negative Predictive Value (NPV) of 100% among 122 NMIBC patients undergoing "conventional" surveillance for NMIBC [56].…”

“…Compared with cytology, Uromonitor presented higher sensitivity than cytology (42.9% cytology sensitivity vs. 73.5% Uromonitor), and when combined with cystoscopy achieved 100% sensitivity and 88.6% specificity, an important upgrade in sensitivity and specificity compared with cystoscopy + cytology combination (sensitivity of 86.7%). [56]. Uromonitor used with cystoscopy at a routine level would lead to a cost-effectiveness increment and might be used in follow-up with better performance relative to the current cytology, when cystoscopy cannot be performed or is not routinely available.…”

Clinical Validation of a Urine Test (Uromonitor-V2®) for the Surveillance of Non-Muscle-Invasive Bladder Cancer Patients

“…Since these alterations present, at this time, some of the most common genetic events in NMIBC tumors, it became imperative to elucidate their potential to detect NMIBC recurrence in urine. In a previous multicenter study on NMIBC patients, in follow-up the test showed promising results with a sensitivity, specificity, and NPV of respectively 100%, 83.8%, and 100% in a subgroup of 24 NMIBC recurrent patients [ 26 ]. With this current study, we aimed to validate these results in an independent cohort of NMIBC patients in follow-up.…”

Illumination of a Vision 2020—Urinary Based Biomarkers for Bladder Cancer on the Way to Clinical Decisions—Dream or Nightmare?

“…Most molecular tests are very expensive and difficult to analyze, but even in that field of diagnostics, there have been attempts to produce commercially available tests with high sensitivity and specificity at lower costs than in previous years. Mutations of TERT and FGFR3 can easily be detected by Uromonitor, a urinary based fast test that showed high sensitivities and specificities in an actual study [14].…”