A COMPARISON BETWEEN MULTIPARAMETRIC MRI AND PHI IN THE PREDICTION OF PROSTATE CANCER AFTER AN INITIAL NEGATIVE BIOPSY

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

Objective

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).

Results

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

Discussions

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.

Conclusion

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.

References

Kim JY et al: Low-Risk Prostate Cancer: The accuracy of
multiparametric MR imaging for detection. Radiology, 2014.
Chamie K: The role of magnetic resonance imaging in
delineating clinically significant prostate cancer. Urology,
2014.
Turkbey B et al: Multiparametric MRI and prostate cancer
diagnosis and risk stratification. Curr Opin Urol, 2012
Aydin H, Kizilgoz V, Tatar IG, Damar C, Ugan AR, Paker I, et al. Detection of prostate cancer with magnetic resonance imaging: optimization of T1-weighted, T2-weighted, dynamic-enhanced T1-weighted, diffusion-weighted imaging apparent diffusion coefficient mapping sequences and MR spectroscopy, correlated with biopsy and histopathological findings. J Comput Assist Tomogr. 2012;36:30–45
Le BV, Griffin CR, Loeb S, Carvalhal GF, Kan D, Baumann NA, Catalona WJ. [-2] Proenzyme prostate specific antigen is more accurate than total and free prostate specific antigen in differentiating prostate cancer from benign disease in a prospective prostate cancer screening study. J Urol. 2010;183:1355–59. [PMC free article] [PubMed]
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med. 2004;350:2239–46. [PubMed]
Hori S, Blanchet JS, McLoughlin J. From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSAs in the detection and management of early prostate cancer. BJU Int. 2013;112:717–28. [PubMed]
Filella X, Foj L, Augé JM, Molina R, Alcover J. Clinical utility of %p2PSA and prostate health index in the detection of prostate cancer. Clin Chem Lab Med. 2014;52:1347–55. [PubMed]

Argomenti: