Commentary - Missing the Mark: Prostate Cancer Upgrading By Systematic Biopsy over MRI/TRUS Fusion Biopsy

Multiparametric MRI (mpMRI) has led to an increase in biopsy detection, while fusion biopsy (FBx) has helped facilitate targeted biopsy of suspicious lesions1. Traditionally done by systematic biopsy (SBx), FBx is able to identify more high-risk cases and less low-risk PCa than SBx2-4. However, there remains a small subset of patients where SBx captures higher grade disease than FBx. The mechanisms as to why FBx fails to capture disease identified by SBx are not completely understood. The aim of this study is to identify predictors for disease upgrading by SBx over FBx, and to define potential mechanisms by which FBx fails to capture CS disease.

A retrospective review was performed on 1003 consecutive patients undergoing mpMRI followed by FBx and SBx at the National Cancer Institute and National Institutes of Heath from 2007-2014. Low-risk disease was defined as Gleason 6 (3+3), intermediate-risk disease as Gleason 7 (3+4 and 4+3), and high-risk disease as Gleason ≥ 8 (4+4); CS PCa was defined as Gleason ≥7. Indepndent re-review of MR imaging, archived biopsy imaging, whole mount pathology, and needle coordinate mapping were conducted. Multivariate logistic regression analysis was performed to determine predictors for upgrading by SBx.

The results of the study found that disease upgrading based on SBx over FBx occurred in 135/1003 (13.5%) patients. The majority of upgrading was due to FBx avoiding detection of Gleason 6 cancers, while in the remaining 62/135 (45.9%), results from SBx revealed intermediate or high-risk disease while FBx showed benign or low-risk disease. Multivariate logistic regression analysis showed that lower PSA (p<0.001), higher mRI prostate volume (p<0.001), and lower number of target cores (p=0.001) were predictors of upgrading by SBx..

The researchers proposed 4 potential mechanisms for failure of FBx in identifying CS disease: mpMRI reader oversight, mpMRI invisible cancers, inaccurate sampling of lesion during FBx due to registration and/or mechanical error, and intra-lesion Gleason heterogeneity. The main mechanisms for under-grading by FBx included mpMRI reader oversight, presence of MR invisible cancer, FBx technique error, and intra-lesion Gleason heterogeneity. In conclusion, MRI and FBx remain highly accurate in detecting the vast majority of PCa, as only 62/1003 (6.2%) cases in the study were upgraded to CS disease by SBx. Additional studies are needed to help elucidate the mechanisms of FBx failure, and identify patients that benefit from SBx in addition to FBx.

Authors: Akhil Muthigi*, BS1 ; Arvin K. George*, MD2 ; Abhinav Sidana, MD1 ; Michael Kongnyuy, MS1 ; Richard Simon, DSc3 ; Vanessa Moreno, MD4 ; Maria J. Merino, MD4 ; Peter L. Choyke, MD5 ; Baris Turkbey, MD5 ; Bradford J. Wood, MD6 ; Peter A. Pinto, MD1

Affiliations: 1Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 2Department of Urology, University of Michigan, Ann Arbor, Michigan. 3Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 4Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 5 Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 6Center for Interventional Oncology, National Cancer Institute & Clinical Center, National Institutes of Health, Bethesda, Maryland

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Reference:

1. George, A. K., Turkbey, B., Valayil, S. G. et al.: A urologist's perspective on prostate cancer imaging: past, present, and future. Abdom Radiol (NY), 2016
2. Valerio, M., Donaldson, I., Emberton, M. et al.: Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review. Eur Urol, 68: 8, 2015 7.
3. Rastinehad, A. R., Turkbey, B., Salami, S. S. et al.: Improving detection of clinically significant prostate cancer: magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy. J Urol, 191: 1749, 2014
4. Rastinehad, A. R., Abboud, S. F., George, A. K. et al.: Reproducibility of Multiparametric MRI and Fusion-Guided Prostate Biopsy: Multi-Institutional External Validation by a Propensity Score Matched Cohort. J Urol, 2016

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