A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2–20 ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2–10 ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25–35, 35–55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25–35, 35–55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n = 397) and for PSA 10–20 ng/ml (n = 439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used. Patient summary: The Prostate Health Index (PHI) blood test helps to identify individuals at higher risk of prostate cancer among Asian and European men, and could significantly reduce unnecessary biopsies and overdiagnosis of prostate cancer. Different PHI reference ranges should be used for different ethnic groups. The Prostate Health Index (PHI) test is effective in cancer risk stratification for both European and Asian men. A higher proportion of biopsies could be avoided among Asian men using PHI. An ethnic-specific reference range should be used.