Ridwan I. Alam, MD, MPH, discusses integrating PHI into prostate cancer diagnostic pathways

In this interview, Ridwan I. Alam, MD, MPH, discusses key findings and clinical implications from the study “Performance of the Prostate Health Index Test in Men with PSA Levels between 10 and 20 ng/mL,” focusing on cohort characteristics, generalizability, and real-world application of PHI in prostate cancer risk stratification.¹

Alam explains that the retrospective cohort demonstrated a reasonably representative racial distribution, with approximately 60% White patients, 20% Black patients, and the remainder comprising other racial groups. Although acknowledging room for improvement, he considers this mix reflective of many clinical practices. Prostate volumes were largely on the higher end, with a median gland size between 50 g and 70 g, which aligns with expectations in men whose prostate-specific antigen (PSA) level falls in the 10 ng/mL to 20 ng/mL range. Family history was intentionally excluded from analysis because of inconsistent documentation in medical records, a common limitation of retrospective studies.

When asked about PHI performance in higher-risk populations or those with different PSA kinetics, Alam notes that emerging evidence suggests certain groups, such as Black men, may have elevated cancer risk regardless of PHI category. Because PHI is derived solely from total PSA, free PSA, and [-2]proPSA, it does not incorporate race or other clinical variables. He emphasizes that clinicians should interpret PHI within a broader clinical context rather than relying on a single numeric output.

Alam highlights PHI’s potential value in settings with limited access to multiparametric MRI, including busy metropolitan centers facing scheduling constraints. In his practice, PHI is used as an initial triage tool: Men in the lowest PHI risk quartile typically do not proceed to MRI, whereas those in higher quartiles undergo further imaging and possible biopsy based on PI-RADS findings.

Regarding acceptable risk thresholds, Alam describes himself as relatively risk-averse, favoring a 5% to 10% miss rate for Grade Group 2 or higher disease when considering biopsy avoidance. He acknowledges variability among clinicians, noting that some accept higher risk, but stresses the importance of shared decision-making and transparent patient counseling.

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