Clinical Utility of Oncuria™, a Multiplexed Liquid Biopsy for the Non-Invasive Detection of Bladder Cancer-A Pilot Study.

Kaoru Murakami,Charles J Rosser,Dave Mori,Hideki Furuya,Ian Pagano,Timothy Daskivich

doi:10.3390/diagnostics12010131

Abstract

Oncuria™ is a validated quantitative multiplex immunoassay capable of detecting bladder cancer from a voided urine sample. Herein, we sought to determine whether Oncuria™ affects physicians’ use of non-invasive and invasive diagnostic tests for microhematuria, gross hematuria, and bladder cancer surveillance. We conducted a survey-based study to assess physician management of nine clinical scenarios involving real-world data from patients with gross hematuria, microhematuria, and bladder cancer on surveillance. We randomly sampled 15 practicing urologists and generated data including 135 patient-by-urologist interactions and 2160 decision points. Urologists recommended a selection of diagnostic tests and procedures before and after Oncuria™ results were provided. We assessed changes in provider use of non-invasive and invasive diagnostic tests after Oncuria™ results were provided. Over 90% of all urologists changed their diagnostic behavior in at least one patient case with the addition of Oncuria™ results. The total number of diagnostic procedures was reduced by 31% following the disclosure of a negative Oncuria™ test and 27% following the disclosure of a positive Oncuria™ test. This is pilot study has the potential to shed light on the analysis of our four large multicenter international studies deploying OncuriaTM. The Oncuria™ urine-based test, a molecular diagnostic capable of ruling out the presence of bladder cancer, reduces both unnecessary invasive and non-invasive diagnostics and has the potential to reduce costs and improve patient outcomes.

Highlights

With the adoption of high-throughput technologies along with sequencing of the human genome almost 20 years ago [1], there has been an explosion of biomarker discovery and validation studies, leading to complex molecular diagnostic tests used to diagnose and stage cancers, to guide therapeutic selection, to assess treatment response, and to detect residual or recurrent cancer [2]
Utilizing the ACCE framework, we previously reported on the analytical validity of OncuriaTM, a quantitative multiplex immunoassay capable of evaluating voided urine samples for the following biomarkers: angiogenin (ANG), apolipoprotein E (APOE), alpha-1 antitrypsin (A1AT), carbonic anhydrase 9 (CA9), interleukin-8 (IL-8), matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 10 (MMP10), plasminogen activator inhibitor 1 (PAI1), syndecan 1 (SDC1), and vascular endothelial growth factor (VEGF), all of which comprised a validated bladder-cancer-associated diagnostic signature [4]
Negative results for OncuriaTM resulted in the following reduction in the use of urine-based tests: 23/41 (56%) cytology, 7/9 (78%) Urovysion, and 4/4 (100%) Bladderchek

Summary

Introduction

With the adoption of high-throughput technologies along with sequencing of the human genome almost 20 years ago [1], there has been an explosion of biomarker discovery and validation studies, leading to complex molecular diagnostic tests used to diagnose and stage cancers, to guide therapeutic selection, to assess treatment response, and to detect residual or recurrent cancer [2]. The integration of molecular diagnostic tests into clinical practice has been inefficient largely due to test variability, a lack of analytical validation, limited robust clinical validation studies, as well as challenges with reimbursements. To address these limitations, the ACCE framework (Analytic Validity, Clinical Validity, Clinical Utility and Ethical, Legal and Social Implications) has been proposed to allow for the collection, evaluation, interpretation, and reporting of key molecular data associated with modern molecular diagnostic tests [3]. The addition of critical demographic data (i.e., age, gender, and race) improved diagnostic performance to an AUROC of 0.95 (95% CI: 0.90–1.00) with an overall sensitivity of 0.93, specificity of 0.93, positive predictive value (PPV) of 0.65, and negative predictive value (NPV) of 0.99 for bladder cancer classification [6]

Methods

Results

Conclusion