Improved Risk Assessment Using a Novel Cancer-Specific Biomarker Assay Derived from Autoantibody Signatures for Men with Non-Aggressive Prostate Cancer Who Are Not Receiving Treatment

Diagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease.To reduce overdiagnosis and overtreatment of indolent disease, a noninvasive and easy-to-administer test is needed to better stratify risk in patients with clinically insignificant disease.For men on active surveillance, such an assay must also be able to help accurately inform whether a prostate biopsy is warranted, and it must be able to more closely monitor patients with non-aggressive disease.Objective: To evaluate the performance of a novel, serum-based multiplexed autoantibody assay plus age versus PSA for discriminating high-grade prostate cancer (Gleason Score 7 or greater) from Gleason 6 among patients who have positive biopsies.Methods: Using retrospective serum samples, the autoantibody assay results were compared with biopsy outcomes in 377 patients (an autoantibody-binding peptide discovery study of 146 samples, a training set of 231 total samples (90 + 141) and a validation cohort comprised of approximately 1/3-2/3 1000X protocol involving a total of 231 samples (90 + 141)) with prostate cancer (Gleason 6 or greater).Samples were sourced from two academic sites and one community clinical facility in the United States.Eligible participants included men aged 40 years or older undergoing a prostate biopsy due to suspicious digital rectal examination finding and/ or elevated PSA level.Results: Among the 377 men (median age 63.2 years; median PSA 7.4 ng/mL), the autoantibody assay plus Age showed better discrimination (Area Under the Curve (AUC) 0.83, 95% CI 0.76-0.90)than PSA alone (AUC 0.60, 95% CI 0.52-0.68)(P =0.001) for separating Gleason Score 7 or greater from Gleason Score 6 in prostate cancer positive patients.For detected Gleason Score 7 or higher test with 95% sensitivity, 24.4% of total biopsies could have been avoided, missing only 3.9% or six (6) patients with Gleason Score 7 disease.Of these six (6) patients whose cancers were missed, a sub-analysis revealed five were Gleason 7 (3+4) and only one was Gleason 7 (4+3). Conclusion:This study evaluated a novel, cancer-specific biomarker assay based on autoantibody signatures that could be used as a noninvasive risk assessment aid for men with non-aggressive disease who are not receiving treatment.When results of this assay are combined with traditional clinical risk factors, risk stratification for high-grade prostate cancer and biopsy decision making are improved compared to current methods in clinical practice.We hypothesize patients with Gleason Score 6 will exhibit the greatest benefits from employing the assay as they may likely avoid both unnecessary prostate biopsy and subsequent overtreatment.We further hypothesize the assay will thus significantly reduce costs to the healthcare system while further improving patient's quality of care.Providers and their patients diagnosed with indolent prostate cancer may consider using this novel assay prior to proceeding with prostate biopsy or other treatments.