High PHI scores are linked to increased odds of significant prostate cancer

In this video, Ridwan I. Alam, MD, MPH, an assistant professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. explored the utility of the Prostate Health Index (PHI) in men with prostate-specific antigen (PSA) levels between 10 and 20 ng/mL—a range above the typical “gray zone” of 4–10 ng/mL where PHI is usually applied.¹

Traditionally, PSA levels in this higher range are presumed to indicate a significant likelihood of clinically important prostate cancer, often prompting immediate biopsy without additional stratification. The investigators aimed to test whether PHI could still provide meaningful risk stratification in this context.

The study retrospectively analyzed 456 biopsy-naive men who underwent PHI testing followed by a prostate biopsy. Findings demonstrated that PHI remained strongly associated with the detection of clinically significant prostate cancer in this cohort. Notably, men in the highest PHI quartile (PHI >55) had an 8.9-fold higher odds of harboring clinically significant cancer compared with those in the lowest quartile, highlighting the potential of PHI to refine risk assessment even at higher PSA levels.

Regarding biopsy methodology, the study encompassed both transrectal and transperineal approaches, reflecting a transition in practice patterns at the institution from 2014 to 2024. Early in the study period, transrectal biopsies predominated, whereas later years saw near-exclusive use of transperineal approaches. A combination of systematic and targeted biopsies was typically employed. Alam noted that, although transperineal biopsies may have a trend toward higher cancer detection in some studies, this study did not find a statistically significant difference between approaches. Therefore, potential verification bias related to biopsy technique was acknowledged but unlikely to meaningfully alter the observed association between PHI levels and detection of clinically significant prostate cancer.

Overall, this study supports the use of PHI as a valuable tool for risk stratification in men with moderately elevated PSA, suggesting that even in higher PSA ranges, PHI can help identify patients at the greatest risk for clinically significant disease.

REFERENCE

1. Holzbeierlein H, Kundu N, Handa N, et al. Performance of the Prostate Health Index test in men with prostate specific antigen levels between 10 and 20 ng/mL. Urology. 2025 Dec 18:S0090-4295(25)01382-2. doi:10.1016/j.urology.2025.12.010