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JU INSIGHT: Impact of Prostate Health Index Results for Prediction of Biopsy Grade Reclassification During Active Surveillance

By: Christopher P. Filson, MD, MS; Kehao Zhu, MS; Yijian Huang, PhD; Yingye Zheng, PhD; Lisa F. Newcomb, PhD; Sierra Williams, BS; James D. Brooks, MD; Peter R. Carroll, MD; Atreya Dash, MD; William J. Ellis, MD; Martin E. Gleave, MD; Michael A. Liss, MD; Frances Martin, MD; Jesse K. McKenney, MD; Todd M. Morgan, MD; Andrew A. Wagner, MD; Lori J. Sokoll, PhD; Martin G. Sanda, MD; Daniel W. Chan, PhD; Daniel W. Lin, MD | Posted on: 01 Nov 2022

Filson CP, Zhu K, Huang Y, et al. Impact of Prostate Health Index results for prediction of biopsy grade reclassification during active surveillance. J Urol. 2022;208(5):1037-1045.

Figure. Decision curve analysis results.

Study Need and Importance

Active surveillance has emerged as a guideline-recommended strategy to avoid detrimental side effects associated with aggressive treatment of low-risk prostate cancer. There is a renewed focus on how to safely decrease the intensity of surveillance biopsies when discovery of higher-grade disease is less likely. Risk calculators using clinical information (eg, prostate-specific antigen level, prior biopsy findings) can help predict clinically significant prostate cancer detection on a surveillance biopsy. We assessed whether results of serum-based biomarker, Prostate Health Index (PHI), can improve predictive capability of existing risk calculators for men pursuing active surveillance and considering a repeat biopsy.

What We Found

Using data from the large Canary Prostate Active Surveillance Study (PASS), we developed different decision rules that incorporated clinical and PHI results and evaluated their ability to predict detection of grade reclassification from Grade Group 1 to Grade Group 2 or higher cancer on a surveillance biopsy. A decision rule combining PHI results with clinical data in a single model (R3) had significantly better discrimination than a rule using clinical data alone (R1; ΔAUC [0.021, 95%CI 0.002–0.041), but only for confirmatory biopsies. A decision curve analysis showed greater net benefit with R3 versus R1 but only at risk thresholds over 15% (see Figure).


It is important to note that many of these biopsies were not performed via MRI-guidance, perhaps limiting generalizing findings to contemporary practice. Furthermore, grade reclassification as an outcome may not adequately reflect tumor aggressiveness in its own right.

Interpretation for Patient Care

Incorporating results of the PHI biomarker may modestly improve the ability to assess risk of grade reclassification for active surveillance patients considering an initial confirmatory biopsy after their diagnosis. However, its role is less clear for men farther along in surveillance considering subsequent biopsies.