Prostate Health Index and multiparametric magnetic resonance imaging to predict prostate cancer grade reclassification in active surveillance

Abstract

Objective To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS). Patients and Methods Between 2014 and 2019, we retrospectively identified 253 consecutive men in the Johns Hopkins AS programme who had mpMRI and PHI followed by a systematic ± targeted biopsy. PHI and PHI density (PHID) were evaluated across Prostate Imaging‐Reporting and Data System version 2.0 (PI‐RADSv2) scores and compared to those with and without GR. Next, the negative predictive value (NPV) and area under the receiver operating curve (AUC) were calculated to compare the diagnostic value of PI‐RADSv2 score combined with PHI, PHID, or prostate‐specific antigen density (PSAD) for GR using their respective first quartile as a cut‐off. Results Of the 253 men, 38 men (15%) had GR. Men with GR had higher PHI values (40.7 vs 32.0, P = 0.001), PHID (0.83 vs 0.57, P = 0.007), and PSAD (0.12 vs 0.10, P = 0.037). A PI‐RADSv2 ≤3 alone had a NPV of 91.6% for GR (AUC 0.67). Using a PHI cut‐off of 25.6 in addition to PI‐RADSv2 ≤3, the NPV and AUC were both increased to 98% and 0.70, respectively. Using a PSAD cut‐off of 0.07 ng/mL/mL with PI‐RADSv2 had an AUC of 0.69 and NPV of 95.4%. PHI and PI‐RADSv2 together could have avoided 20% of biopsies at the cost of missing 2.6% of GRs. Conclusions The combination of PHI and mpMRI can aid in the prediction of GR in men on AS and may be useful for decreasing the burden of surveillance prostate biopsies.

Prediction of Grade Reclassification of Prostate Cancer Patients on Active Surveillance through the Combination of a Three-miRNA Signature and Selected Clinical Variables

“…The miRNA-based signature presented here explores the possibility to better define aggressive vs. indolent diseases by using a blood biomarker. In terms of AUC value, our signature was comparable to that observed with the three-miRNA score proposed by Liu et al [ 25 ] as well as with PHI [ 8 ] and PCA3 [ 9 ] in the AS setting.…”

“…However, due to the unavailability of tissue samples for the majority of patients, we could not investigate whether such a predictive value is maintained on subsequent biopsies. In this context, other circulating biomarkers, such as PHI and PCA3 , assessed on baseline samples improved the accuracy of predicting reclassification at the first surveillance biopsy but did not provide further value over clinical variables on subsequent biopsies [ 8 , 9 ].…”

“…For instance, the serum 4Kscore, which evaluates a panel of four kallikrein proteins (total PSA, free PSA, intact PSA and human kallikrein-related peptidase 2) combined with clinical parameters, was found to improve the accuracy of predicting reclassification at the first surveillance biopsy in the multi-institutional Canary Prostate Active Surveillance Study (PASS) [ 7 ]. Another serum PSA-based biomarker, the prostate health index (PHI), a mathematical formula consisting of total PSA, free PSA and [−2]proPSA isoform of PSA, was found to be predictive of grade reclassification in the Johns Hopkins AS cohort [ 8 ]. Moreover, urinary prostate cancer antigen 3 ( PCA3 ) proved to be associated with reclassification at the first repeated biopsy in the PASS cohort [ 9 ].…”

Biomarker in Active Surveillance for Prostate Cancer: A Systematic Review

“…More recently, Schwen et al [ 38 ] combined the PHI and mpMRI to predict biopsy reclassification among 253 patients with NCCN low-risk or very low-risk PCa in a retrospective study. In this study PHI and mpMRI would have avoided nearly 20% surveillance biopsies.…”

PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer

“…Patients with higher PHI values had a higher chance of reclassification. A PHI score under 25.6 and a Prostate Imaging-Reporting and Data System (PI-RADS)v2 lesions ≤3, could help avoid 20% of prostate biopsies while missing only 2.6% that would have been reclassified, but if MRI examination is negative, as many as 41% of biopsies could be bypassed while missing 11% of tumors that would have been reclassified [ 42 ].…”