Abstract A066: Performance of the prostate health index (PHI) assay in black men
Authors: Carbunaru Samuel , Nettey Oluwarotimi , Schaeffer Edward M , Gann Peter H , Abern Michael , Hollowell Courtney M.P , Watson Karriem , McDowell Tiffany , Kittles Rick A , Murphy Adam B 
Published: September 2020

Abstract
Introduction: The low specificity of PSA in prostate cancer (PCa) screening has caused excessive biopsies and PCa over-detection. PHI is more specific for clinically significant (cs) PCa (i.e. Gleason &gt;6 PCa) and includes serum PSA, [-2]proPSA, and free PSA in its formula. Validation studies in diverse populations have suggested that PHI should be used as a reflex test and the optimal cutoffs for PHI vary across ethnic groups, but have not been determined in Black men. We sought to 1) assess the distributions of PHI and PSA in healthy controls and men with high-grade PCa and 2) assess the accuracy of PHI vs. PSA for detection of csPCa in Black men with elevated PSA. Methods: The present study population consists of two biopsy-naïve cohorts. The first cohort serves as healthy controls and includes Black men with PHI and PSA drawn at community screening events through the social networks of eight lay Black male Citizen Scientists. The second PHI Biopsy Study cohort consists of Black men referred with elevated PSA and/or abnormal digital rectal exam (DRE) who had PHI drawn immediately before prostate biopsy. We excluded men with prior biopsies or known PCa. Distributions of PHI and PSA were compared across controls and men with negative biopsies, Gleason 6 PCa and csPCa. Among men with biopsy, we compared the area under the receiver operating characteristics curves (AUC) for PSA and PHI for detecting csPCa and assessed specificity at selected sensitivities as a proxy of avoided biopsies. We descriptively assessed theoretically avoided biopsies and missed csPCa at previously established PHI cut points [27.0, 28.6, 29.9, and 35.0]. Results: For the first objective, 139 men (42.5%) were included as controls from the Citizens Scientist Study and 188 (57.5%) were from the PHI Biopsy Study cohort, out of which 82 (43.6%) had a negative biopsy for PCa, 40 (21.1%) had low-grade PCa, and 66 (35.1%) had a Gleason &gt;6 PCa. Compared to the healthy control group, the PHI Biopsy Study cohort was older (median age 61 vs. 55 years), with higher PSA levels (7.1ng/mL vs. 0.9ng/mL) and PHI scores (61.1 vs. 20.1), and more commonly had a family history of PCa (19.4% vs. 5.0%) and benign prostatic hyperplasia diagnosis (21.3% vs. 2.2%) (all p&lt;0.001). Relative to PSA, PHI has a higher degree of overlap in the distribution between controls and csPCas (p &lt;0.05), suggesting PHI would not perform well as a primary screening test in Blacks. In men with PSA between 4-10, PHI outperformed PSA in the detection of HGPCa with an AUC of 0.70 (95% CI: 0.59-0.81) compared to 0.57 (95% CI: 0.46-0.69). As a reflex test in men with PSA of 4-10ng/mL and normal DRE, a PHI cutoff of 35.0 would spare 20 (27.8%) low-risk men a biopsy while missing 2 (7.4%) csPCas. Conclusion: PHI should not be used for primary screening but has higher accuracy and specificity than PSA in Black men with PSA levels of 4-10ng/mL as a reflex test. At a cutoff of 35.0, 28% of low-risk men avoid biopsy while missing 7% of csPCas.
Citation Format: Samuel Carbunaru, Oluwarotimi Nettey, Edward M Schaeffer, Peter H Gann, Michael Abern, Courtney M.P Hollowell, Karriem Watson, Tiffany McDowell, Rick A Kittles, Adam B Murphy. Performance of the prostate health index (PHI) assay in black men [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A066.