Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

Jinan Guo,Wanlong Tan,Athanasios Simoulis,Per-Anders Abrahamsson,Chang Zou,Heather Johnson,Allan Johnson,Taolin Xia,Lukas Kenner,Alan H B Wu,Kefeng Xiao,Heqiu Zhang,Jenny L Persson,Xuhui Zhang,Nishtman Dizeyi,Xiaoyan Feng,Fei Li,Lingwu Chen

doi:10.3389/fmed.2021.721554

Abstract

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available.Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups.Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892–0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935–0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1–3 cancer subgroups.Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Highlights

Prostate cancer (PCa) is a prevalent cancer in men and a leading cause of cancer-related deaths
The National Comprehensive Cancer Network (NCCN) guidelines classify PCa into five risk groups and recommend that most patients in the very high, high, and unfavorable intermediate risk groups receive treatment, while most patients in the very low, low, and favorable intermediate risk groups are placed on active surveillance
The very high, high, and unfavorable intermediate risk groups can be classified as clinically significant PCa, and the very low, low, and favorable intermediate risk groups are classified as clinically insignificant PCa

Summary

Introduction

Prostate cancer (PCa) is a prevalent cancer in men and a leading cause of cancer-related deaths. With the widespread use of prostate-specific antigen (PSA) screening, a large number of PCa are diagnosed and treated, leading to over-treatment of many early stage cases without significant clinical symptoms or life risk. Magnetic resonance imaging (MRI) and multiparametric MRI are non-invasive imaging tools for PCa diagnosis with the ability to significantly reduce the number of unnecessary repeat prostate biopsies, but their accuracy to detect clinically significant PCa is limited by large false-negative rates [7,8,9,10]. Most of them were not tested for stratification of clinically significant and insignificant cancer but discriminated cancer risk groups, and no biomarker or biomarker panels have shown high diagnostic accuracy [11,12,13]. The development of more accurate tests is urgently needed

Methods

Results

Conclusion