Clinical utility of a serum biomarker panel in distinguishing prostate cancer from benign prostate hyperplasia

Michael A Kiebish,Michele Petrovic,Alagarsamy Srinivasan,Leonardo O Rodrigues,Amina Ali,Albert Dobi,Shiv Srivastava,Jeonifer Garren,Elder Granger,Shobha Ravipaty,Tracey Friss,Jennifer Cullen,David G Mcleod,Viatcheslav R Akmaev,Poornima Tekumalla,Shen Luan,Mark D Kellogg,Sunil Patil ,Allison Klotz,Stephen J Freedland,Neil Fleshner,Eleftherios P Diamandis ,Inger L Rosner,Nischal Mahaveer Chand,Sandra Laszlo,C Bountra ,Wei Wu ,Greg Miller,Rangaprasad Sarangarajan,Niven R Narain

doi:10.1038/s41598-021-94438-4

Abstract

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5–7 (AUC 0.76 vs. 0.56) and Gleason scores of 8–10 (AUC 0.74 vs. 0.47). With Gleason scores (8–10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.

Highlights

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa
There are several commercially available tests including the K4Score test, which has been tested in Europe and the U.S, and can discriminate between high-risk and low-risk disease[13] as well as the prostate health index (PHI) test that can discriminate between high-risk and low-risk cancers, but may not be able to accurately predict disease severity when challenged with intermediate PSA values[14,15,16]
The performance of the biomarker panel indicated that in the current study cohort (n = 777 patients), 130 (43%) patients without PCa would not be recommended for biopsy, reducing the number of unnecessary biopsies compared to all 300 patients with PSA alone who would have been recommended for a biopsy

Summary

Introduction

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. With Gleason scores (8–10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, preventing unnecessary biopsies. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20817, USA. The lack of specificity of prostate cancer screening using PSA testing is driven in large part by the co-incidence of benign prostate hyperplasia (BPH), a condition which can result in increased PSA levels, in this patient population[7]. None of them have been extensively evaluated in men with BPH

Methods

Results

Conclusion