RADIOLOGY CORNER The Role of Imaging on the Diagnosis of Benign Prostatic Hyperplasia versus Prostate Cancer
By: Masatomo Kaneko, MD, PhD; Andrew Chen, MD; Donya S. Jadvar; Inderbir S. Gill, MD; Andre Luis Abreu, MD | Posted on: 01 Sep 2022
Diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer (PCa) can be difficult to differentiate. Although prostate biopsy (PBx) is the gold standard for PCa diagnosis, it is associated with a risk of infection, rectal bleeding, acute urinary retention, and pain. Therefore, performing PBx should be minimized when clinically appropriate. Multiparametric magnetic resonance imaging (mpMRI) has emerged as an important adjunct in detection and evaluation of clinically significant PCa (CSPCa) and is currently recommended by guidelines for all men with a suspicion for PCa prior to PBx.1 Prostate Imaging–Reporting and Data System® (PI-RADS®) is the standard for mpMRI acquisition and interpretation for PCa diagnosis. The current version v2.1 was revised in 2019, which included differentiation of BPH nodule and PCa suspicious nodule.2 Although typical BPH nodules were assigned a T2 weighted (T2W) score of 2 on PI-RADS v2, they are now assigned a score of 1 on v2.1. That is because BPH nodules are highly unlikely to harbor CSPCa. Another important change was the role of diffusion weighted imaging (DWI) score to differentiate atypical transitional zone (TZ) nodules. TZ nodules are upgraded to PI-RADS score of 3 if they are evaluated as DWI score ≥4.
MRI for PCa Diagnosis and Lesion Localization
PI-RADS correlates with PCa aggressiveness; therefore, mpMRI can be used as an important biomarker for PCa diagnosis. A recent meta-analysis showed the PCa and CSPCa detection according to PI-RADSv2.1 score were 3% and 2% for PI-RADS 1, 9% and 4% for PI-RADS 2, 34% and 20% for PI-RADS 3, 70% and 52% for PI-RADS 4, and 97% and 85% for PI-RADS 5.3 MRI pathway detects more CSPCa than systematic PBx (SBx).4 Patients with a small lesion in large prostate, anterior cancer lesion, or prior negative biopsy history are the most challenging cases for transrectal ultrasound (TRUS) SBx.5 mpMRI guided targeted PBx can precisely detect and localize CSPCa in challenging cases (Fig. 1).
PBx Can Be Safely Avoided in Differentiating BPH versus PCa in Selected Patients
Ahmed et al demonstrated mpMRI to triage men with elevated PSA without previous PBx history would decrease unnecessary PBx by 27%.6 Some investigators reported that MRI and clinical parameters including age, African American race, prior negative PBx history, abnormal digital rectal examination, PSA, PSA density, and PI-RADS score were predictors for CSPCa detection.7,8
Combination of clinical and imaging features contributes to more accurate CSPCa detection than clinical or imaging features alone. Mehralivand et al found “clinical parameters only model” and “clinical + MRI-derived parameters model” could avoid 4% and 18% fewer unnecessary biopsies without missing CSPCa, compared to performing a biopsy to all patients with positive MRI results.8
Oishi et al evaluated men with negative mpMRI findings and found that a PSA density <0.15 ng/ml2 with prior negative PBx history yielded a high negative predictive value in determining CSPCa on PBx.7 To safely avoid PBx for patients with persistent elevated PSA and large prostate, the combination of clinical features including PSA density less than 0.15 ng/ml2 and previous negative PBx history and PI-RADS 1-2 as imaging features should be considered (Fig. 2). These parameters are important for differentiating BPH vs PCa in scenarios of persistent PSA elevation and prostate enlargement.
Managing Patients with BPH and Persistent Suspicion for PCa
Approximately 15% of CSPCas are MRI invisible.7 Current diagnostic biomarkers including the prostate health index (PHI), 4Kscore®, SelectMDx, ConfirmMDx, PCA3, MiPS, and ExoDX™ can help stratify the risk of PCa vs BPH.9 The diagnostic accuracy of these markers is higher than PSA. The combination of biomarkers and imaging diagnostics is a promising field. When PHI was combined with mpMRI, the area under the curve (AUC) for CSPCa detection was 0.75, compared to mpMRI and PSA alone (AUC=0.64 and 0.69). The combination model of 4K and PHI score could reduce 29% of PBx. Although these improvements have not been confirmed across all settings, these innovative biomarkers can aid in clinical decision making and contribute to safely avoiding unnecessary PBx. When a high clinical suspicion of PCa persists in the patient with elevated PSA, negative mpMRI, and previous negative biopsies, these biomarkers are useful in determining whether a saturation biopsy would be appropriate.
Multi-modal evaluation combining clinical features, imaging modalities, and novel biomarkers can safely reduce unnecessary PBx on patients with BPH.
Combination of MRI and Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) for Evaluation of BPH versus PCa
MRI has several contraindications and limitations including pacemakers, metallic foreign body, claustrophobia, reactions to the contrast agent, lower inter-rater agreement, MRI invisible PCa, and others. Currently, significant advances to develop more sensitive imaging techniques for PCa detection include PET scanning.10
PSMA enzyme activity is known to be significantly elevated in PCa when compared to benign prostate tissue and BPH (Fig. 3). PSMA PET scan has been approved by the Food and Drug Administration for staging of patients at high risk of PCa metastasis, as well as for evaluation of biochemical failure. PSMA PET has shown an excellent safety profile with almost no adverse events.10 In addition, PSMA PET can be used as a biomarker to select patients for PSMA-targeted radioligand therapy.
The use of PSMA PET for patients prior to PBx has been less studied. In the case that MRI results are inconclusive or biopsy results are negative, further supportive evidence for the use of PSMA PET can potentially emerge. Furthermore, 18F-FDG (fluorodeoxyglucose) PET/computerized tomography may provide added value in identifying 18F-FDG-positive, PSMA negative disease.10 Of note, since PSMA expression is heterogeneous, it can result in false-negatives both in primary tumors and metastases. PRIMARY, the multicenter, prospective, cross-sectional clinical trial, will provide evidence on the additional value of PSMA PET to mpMRI for CSPCa detection in men undergoing initial PBx.
- Bjurlin MA, Carroll PR, Eggener S, et al. Update of the standard operating procedure on the use of multiparametric magnetic resonance imaging for the diagnosis, staging and management of prostate cancer. J Urol. 2020;203(4):706-712.
- Turkbey B, Rosenkrantz AB, Haider MA, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 update of Prostate Imaging Reporting and Data System Version 2. Eur Urol. 2019;76(3):340-351.
- Oerther B, Engel H, Bamberg F, Sigle A, Gratzke C, Benndorf M. Cancer detection rates of the PI-RADSv2.1 assessment categories: systematic review and meta-analysis on lesion level and patient level. Prostate Cancer Prostatic Dis. 2022;25(2):256-263.
- Drost F-JH, Osses DF, Nieboer D, et al. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev. 2019;4(4).
- Schouten MG, van der Leest M, Pokorny M, et al. Why and where do we miss significant prostate cancer with multi-parametric magnetic resonance imaging followed by magnetic resonance-guided and transrectal ultrasound-guided biopsy in biopsy-naïve men? Eur Urol. 2017;71(6):896-903.
- Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815-822.
- Oishi M, Shin T, Ohe C, et al. Which patients with negative magnetic resonance imaging can safely avoid biopsy for prostate cancer? J Urol. 2019;201(2):268-276.
- Mehralivand S, Shih JH, Rais-Bahrami S, et al. A magnetic resonance imaging–based prediction model for prostate biopsy risk stratification. JAMA Oncol. 2018;4(5):678-685.
- Kretschmer A, Tilki D. Biomarkers in prostate cancer—current clinical utility and future perspectives. Crit Rev Oncol Hematol. 2017;120:180-193.
- Jadvar H, Calais J, Fanti S, et al. Appropriate use criteria for prostate-specific membrane antigen PET imaging. J Nucl Med. 2022;63(1):59-68.