Introduction: In the last decade, there is increasing evidence for the diagnostic performance of MRI prostate for the detection of prostate cancer. The MRI pathway detected insignificant prostate cancer (insignPCa) in 14% of patients, as compared to the TRUSGB pathway which detected 25% of patients with insignPCa. Not performing TRUS biopsy is at the cost of missing csPCa only in 4%. In addition, multiparametric MRI (mpMRI) was able to detect more clinically significant and less clinically insignificant cancers, whilst enabling a significant proportion of patients to avoid an unnecessary biopsy. However, these studies were performed in biopsy-naïve patient and the role of mpMRI in men with prior negative biopsies have not been well defined.
This study aims to review the role of serum biomarkers: prostate-specific antigen (PSA), PSA density (PSAD), free:total PSA ratio, prostate health index (PHI), and PHI density (PHID), along with magnetic resonance imaging (MRI) for identification of clinically significant prostate cancer (PCa), comparing their utility in patients with persistently raised PSA levels after a prior negative prostate biopsy (PNB).
Methods: In this single-centre prospective observational study conducted from September 2015 to October 2020, patients underwent a saturation biopsy via the transperineal route. If a Prostate Imaging Reporting and Data System version 2 (PIRADS) 3 and above lesion were seen on MRI, targeted biopsies were also obtained. The serum biomarkers prostate-specific antigen, PSA density, free:total PSA ratio, PHI, and PHI density, were evaluated in the cohort for prediction of prostate cancer, as well as clinically significant prostate cancer, defined as a Gleason grade group 2 or more. Logistic regression models were used to generate receiver operating curves (ROC) for the 3 biomarkers. The sensitivity, specificity, and Area Under Curve (AUC) for each of the biomarkers were also determined.
Results: 351 men underwent saturation biopsy with or without targeted biopsies. 103 patients had a PNB. Among this PNB cohort, 43 (41.7%) men had a benign outcome, while 60 (58.3%) men had histopathologically diagnosed PCa, of which 41 (39%) were clinically significant. All patients underwent multiparametric MRI scans prior to biopsy. Within this cohort, PHI and PHID had the best abilities to predict for clinically significant PCa with an AUC of 0.73 and 0.70 respectively, compared to 0.65 for PSAD, 0.34 for free:total PSA, and 0.56 for PSA.
Discussion & Conclusion: There is a trend towards MRI and repeat prostate biopsy following a negative first biopsy. mpMRI is known to have a high specificity and sensitivity for detecting clinically significant cancers. However, it is an expensive and resource intensive investigation. Furthermore, it has a false negative rate of 9% (27/300) in the detection of grade 2 or higher PCa. Moreover, studies have shown significant procedure-related stress in this group of patients. Hence there is a pressing need to provide a more definitive answer to this group of patients.
A significant proportion of patients are diagnosed with PCa after a PNB. This study shows that PHI and PHI densities may be suitable adjuncts for predicting clinically significant PCa in patients with PNB. Additionally, our study also highlights the utility of free:total PSA. While PHI had the best ability to predict clinically significant PCa with an AUC of 0.73, the AUC of 0.34 for free:total PSA suggests an inverse correlation. Hence, the free:total PSA has a negative predictive value for clinically significant PCa.
Written by: Dr. Chan Ming Tow, Department of Urology, National University Hospital Singapore, Singapore