摘要：Background: To reduce over diagnosis and overtreatment of prostate cancer, a noninvasive and easy to administer test is needed to assess the risk of clinically significant disease. Such an assay must also be able to help accurately inform whether a prostate biopsy is warranted. Objective: To determine the performance of a novel, serum-based multiplexed autoantibody assay vs. PSA for discriminating high-grade prostate cancer on biopsy (Gleason Score 7 or greater). Methods: Using retrospective serum samples, we compared the autoantibody assay results with biopsy outcomes in 760 patients (an autoantibody-binding peptide discovery study of 268 samples, a training set of 196 samples and a validation cohort comprised of 296 samples) with or at risk of prostate cancer 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 196 men in the training set (average age 61.9, average PSA 7.4 ng/mL), the autoantibody assay plus age showed better discrimination (Area Under the Curve (AUC) 0.74, 95% CI (0.68-0.80)) when compared to PSA alone (AUC 0.56, 95% CI (0.54-0.68)). Based on an assumed clinical decision for patients falling below the test cut point, 31.6% of unnecessary biopsies could have been avoided. Among the 296 men in the validation study (average age 63.3 years, range 40-90; average PSA 6.0 ng/mL), the autoantibody assay showed better discrimination (AUC 0.69, 95% CI 0.63-0.75) than PSA (AUC 0.55, 95% CI 0.48-0.62) (P =0.007) for separating Gleason Score 7 or greater from Gleason Score 6 and patients negative on biopsy. For detected Gleason Score 7 or higher test with 95% sensitivity, 20.1% of unnecessary biopsies could have been avoided, missing only 4.9% of patients with Gleason Score 7 disease. Of these 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 high-grade prostate cancer. 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 suspected of having prostate cancer may consider using this novel assay prior to proceeding with prostate biopsy.
