Andrea Fandella1, Stefano Guazzieri1
  • 1 Casa di Cura Giovanni XXIII (Monastier di Treviso)


The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis.
Prostate Health Index (PHI) and prostate multiparametric Magnetic Resonance Imaging (mp-MRI) have
been proposed for reducing the number of unnecessary repeated biopsies (RB) in patients with a negative prostate biopsy (PB) and persistent suspicion of prostate cancer (PCa).
We conducted this study to evaluate the diagnostic accuracy of PHI, and mp-MRI, and different combinations of these tests in the RB setting.

Materials and Methods

79 patients with an initial negative prostate biopsy and persistent suspicion of PCa were enrolled in this prospective study. The patients underwent serum measurements of the total PSA and free PSA rate, along with PHI, and mp-MRI (receiver operating characteristics (ROC) curve for ADC values, choline (Cho)/citrate (Cit) and Cho+creatine (Cre)/Cit ratios for each observer) prior to standard (12- core) RB that was performed by urologists blinded to the mp-MRI results. Multivariable logistic regression models with different combinations of PHI, and mp-MRI were used to identify the predictors of PCa with RB, and the performances of these models were compared using ROC curves, AUC analysis, and decision curve analysis (DCA).


The Prostate Health Index was significantly higher in men with Gleason 7 or greater and "Epstein significant" cancer
For mp-MRI sensitivity declined to 31% and specificity to 75% for the T1W sequence, sensitivity declined to 43% and specificity to 67% for the DCE T1W sequence, sensitivity declined to 46% and specificity to 68% for the T2W sequence, sensitivity declined to 29% and specificity to 82% for the DWI-ADC mapping; and specificity was 49% for the Cho/Cit and Cho+Cre/Cit ratios, sensitivity was 69% for the Cho/Cit ratio, and sensitivity was 70% for the Cho+Cre/Cit ratio for H-MRS. The T2W sequence and H-MRS presented significant statistical differences for the depiction of prostatic cancer (P < 0.05), the most efficient sequence to detect prostatic cancer was H-MRS: Cho+Cre/Cit and Cho/Cit ratios. In the ROC analysis, the most significant contribution was provided by mp-MRI (AUC value of 0.936), which was
greater than the contribution of the PHI model (p<0.001). In the multivariate logistic regression analysis, only mp-MRI was a significant independent predictor of PCa diagnosis with RB (p<0.001).
The results of the DCA confirmed that the most significant improvement in the net benefit was provided by mp-MRI


It is well known that precise diagnosis faces real limitations with digital rectal examination, serum PSA, diagnostic imaging, and PBx . Over the past decades, the use of serum PSA has significantly improved the clinical management of PCa and decreased PCa-specific mortality despite its unsatisfactory specificity and sensitivity. As the novel markers, PHI and %p2PSA have been suggested the most cancer-specific serum biomarkers in men with PCa in comparison with other currently available test (tPSA, fPSA and %fPSA), especially in patients with PSA < 10 ng/ml. MRI has already been established as a noninvasive diagnostic tool . However, the ideal MRI sequence modality combination has yet to be established.
In our study, DWI had the highest specificity, PPV, NPV, and AUC to detect the presence or absence of PCa in intraprostatic segmental regions . We could obtain similar analytical results only in Pz regions. It was reported that DWI provides an important quantitative biophysical parameter that can be used to differentiate benign from malignant prostate tissue . In the European Society of Urogenital Radiology (ESUR) prostate MR guidelines (2012) , DWI is noted to be a powerful clinical tool, as it allows apparent diffusion coefficient (ADC) maps to be calculated, enabling qualitative and quantitative assessment of PCa aggressiveness. Even though we did not use an ADC map in this study, DWI had the best outcome among the MRI modalities.


PHI test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis.
Growing body of evidence suggested that %p2PSA and PHI are more accurate in distinguishing indolent PCa from more aggressive diseases. However, the limitations of those studies must be noticed. First, the recommended cut-off point of these indexes among those studies varied widely . So far, the standard thresholds of PHI and %p2PSA to identify PCa and aggressive disease have not been set up.
Our results indicate that mp-MRI has high diagnostic accuracy in identifying patients with PCa in the RB setting compared with PHI. For this reason, mp-MRI should be considered as a valid tool for avoiding
unnecessary biopsies in this clinical scenario.


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