Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Urologic Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Urologic Diseases

Transitional Cell Carcinoma

Bladder urine samples (\> 10 ml) will be collected for cytology and for the methylation test before cystoscopy. Prior to semirigid and flexible ureteroscopy, urine specimens from the upper urinary tract will be obtained via a ureteral catheter.

Urine biomarker

Andrea Gallioli, MD

Alberto Breda, MD

Background:

Upper tract urothelial carcinoma (UTUC) is a rare tumor associated with bladder cancer in up to 50% of cases. Its incidence is rising due to improved detection and bladder cancer survival. The diagnosis of UTUC is challenging because more than 35% of the standard biopsies can result inconclusive. The grading of UTUC cells, which delivers the most important data for the choice between a kidney-sparing surgery (KSS) and a radical treatment, is upgraded in 30% of radical nephroureterectomies. The follow-up of UTUC after KSS requires an invasive procedure as a diagnostic ureteroscopy for a minimum of 5 years, and urinary cytology has low diagnostic power.

Objective:

The aim of the study is to evaluate the accuracy (overall and stratified for grade) of a DNA methylation urine biomarker test (Bladder EpiCheckTM) in UTUC, and to compare it with current standard (urinary cytology). The secondary objective is to show its applicability in the specific clinical scenario of UTUC surveillance after kidney-sparing surgery and related cost-effectiveness.

Design, Setting, and Participants:

From February 2019 to February 2021, 80 consecutive patients candidates to ureteroscopy for suspicion of primary, recurrent or metachronous UTUC in one tertiary Referral Centers (Fundaciò Puigvert) giving written informed consent will be included in the study.

Intervention:

Bladder urine samples (\> 10 ml) will be collected for cytology and for the methylation test before cystoscopy. Prior to semirigid and flexible ureteroscopy, urine specimens from the upper urinary tract will be obtained via a ureteral catheter.

Urine from upper urinary tract and bladder (at least 10 ml each)

Genetic Testing in Upper Tract Urothelial Carcinoma (UTUC): the Epicheck Study

To test the accuracy of the urine biomarker

To evaluate and compare performance of urinary cytology and urine biormarker

To compare the accuracy of the test in situ (upper tract) and in the bladder

Sub-analysis on biormaker accuracy for low and high grade tumours

A decision-making analysis will be performed in patients with UTUC suspicion, reporting the net benefit, the number of unnecessary ureteroscopies avoided

Nucleix Ltd.

Fundacio Puigvert

Chief of the Uro-Oncology Unit and Director of the Kidney Transplantation Division

Symptoms and General Pathology

Urinary Bladder Neoplasms

Hematuria

Urinary Bladder Diseases

Urination Disorders

Hemorrhage

In the ''care-as-usual'' arm, all patients undergo 'care-as-usual', i.e. a cystoscopy and upper tract imaging (ultrasound or CT-scan)

In the intervention arm, the urine test is used to triage patients for a diagnostic workup ('urine-first' strategy). Only patients with an abnormal test result undergo cystoscopy and upper tract imaging.

Only patients with an abnormal urine test result undergo a diagnostic workup, i.e. cystoscopy and upper-tract imaging.

urine-first strategy

J.L. Boormans, Prof. MD

O.M. Pijpers, MD

The SeARCH-trial assess the clinical impact of a molecular urine test as a 'urine-first' strategy in the diagnostic workup of patients presenting with microscopic hematuria.

Microscopic hematuria (MH) can be a sign of an underlying disease, including malignancy of the urinary tract, and is reason for referral to a urology clinic. The current standard diagnostic workup for MH patients includes visual inspection of the bladder by cystoscopy and upper tract imaging to rule out the presence of a tumor in the urinary tract. However, the a priori risk of cancer in patients with MH is only 2-5%. Consequently, 95% of MH patients unnecessarily undergo invasive procedures, which are: I) uncomfortable and stressful for patients, II) has a significant impact on limited available (financial) resources and III) a CT scan is accompanied by exposure to ionizing radiation.

Previously we developed a molecular urine assay to detect urinary tract cancer in hematuria patients that had robust diagnostic performance; a negative predictive value \>99%, sensitivity, and specificity \>90%. The SeARCH-trial evaluates the clinical impact of a urine assay as a 'urine-first' strategy, meaning that only patients with an abnormal urine test results undergo invasive diagnostics. In this multicenter stepped-wedge cluster randomized trial we compare clinical outcomes by using a 'urine-first' strategy to 'care-as-usual', which is a cystoscopy and upper tract imaging in all patients presenting with MH. In addition, we assess patients' preferences, patients reported outcome measurements, and healthcare costs to show that a 'urine-first' strategy improves patients' quality of life and results in a more appropriate use of limited available resources.

A multicenter, stepped wedge cluster randomized trial

This is a stepped wedge cluster randomized clinical trial

Safely Reduce Cystoscopic Evaluations for Hematuria Patients

The net benefit is defined as the proportion of patients who were diagnose with urinary tract cancer within 1 year after initial diagnostic work-up in the population (true positives) subtracted by the proportion of patients that underwent diagnostic evaluations without an abnormal finding (false positives). The latter is multiplied by the decision threshold, which represents the estimated harms of the diagnostic intervention, such as patients' burden and use of available resources, against the harms of an outcome event, i.e. missing a urinary tract tumor.

This will be performed according to the Dutch guideline by administering validated questionnaires.

Patient-reported outcome measurements (PROMs) are assessed for patients undergoing cystoscopy and urine collection.

Erasmus Medical Center

Professor

Recurrence

Non-Muscle Invasive Bladder Neoplasms

Disease Attributes

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Patients with a previous diagnosis of non-muscle invasive bladder cancer, attending a urology clinic for the purposes of bladder cancer recurrence monitoring.

ADXBLADDER is a non-invasive, qualitative ELISA utilising a combination of two monoclonal antibodies for the detection of MCM5 in urine sediment. It is intended to aid in the monitoring of bladder cancer recurrence in non-muscle-invasive bladder cancer patients. Participants will be asked to provide a full void urine specimen, which will be centrifuged before the urine sediment is lysed. The lysed sample will then be tested with ADXBLADDER.

ADXBLADDER

Jacqueline Stockley, PhD

Larry Karsh, MD

Martin K. Deneen, MD

James Bailen, MD

Jason Hafron, MD

Louis Keeler, MD

Christopher Pieczonka, MD

Lawrence A. Gervasi, MD

Laurence Belkoff, MD

Neal Shore, MD

Jose De La Cerda, MD

Eugene Kramolowsky, MD

Michael Williams, MD

Raymond Lance, MD

Professor Ashish Kamat

The objective of this prospective, multi-centre study is to evaluate the performance of ADXBLADDER, a urine MCM5 ELISA test, as an aid in the detection of bladder cancer recurrence. Patients undergoing cystoscopic surveillance in non-muscle invasive bladder cancer (NMIBC) follow-up will be recruited and asked to provide a urine sample to be tested with ADXBLADDER. To assess the diagnostic accuracy of the test, the MCM5 results will be compared with the gold standard cystoscopy and pathology of resected tissue.

A Performance Evaluation Study of Arquer's MCM5 Elisa Test (ADXBLADDER) to Aid in the Monitoring of Recurrence in Non-Muscle Invasive Bladder Cancer

The ADXBLADDER MCM5 results will be compared with the definitive diagnosis obtained by gold standard cystoscopy and pathological assessment of suspicious lesion(s) (where clinically indicated).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genetic Testing in Upper Tract Urothelial Carcinoma (UTUC): the Epicheck Study	NCT04702347	Urologic Cancer Urologic Neopla...	Urine biomarker	18 Years -	Fundacio Puigvert
Safely Reduce Cystoscopic Evaluations for Hematuria Patients	NCT06026189	Hematuria Urothelial Neop... Urothelial Carc... Bladder Cancer	urine-first str...	-	Erasmus Medical Center
Safely Reduce Cystoscopic Evaluations for Hematuria Patients	NCT06026189	Hematuria Urothelial Neop... Urothelial Carc... Bladder Cancer	urine-first str...	-	Erasmus Medical Center
Genetic Testing in Upper Tract Urothelial Carcinoma (UTUC): the Epicheck Study	NCT04702347	Urologic Cancer Urologic Neopla...	Urine biomarker	18 Years -	Fundacio Puigvert
A Performance Evaluation Study of Arquer's MCM5 Elisa Test (ADXBLADDER) to Aid in the Monitoring of Recurrence in Non-Muscle Invasive Bladder Cancer	NCT05508568	Bladder Cancer	ADXBLADDER	22 Years -	Arquer Diagnostics Ltd

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