MR-US Fusion Guided Biopsy: Is it fulfilling expectations?

MR-US Fusion Guided Biopsy: Is it fulfilling expectations? Kenneth L. Gage MD, PhD Assistant Member Department of Diagnostic Imaging and Interventional Radiology 4 th Annual New Frontiers in Urologic Oncology Sandpearl Resort, Clearwater Beach, FL November 2-4, 2017

Disclosure No financial disclosures or potential conflicts of interest

Outline Brief Overview of Prostate Cancer ü The Radiologist Perspective Desire for Directed Biopsies Review MR-US Fusion Biopsy Experience Established? and Developing Applications Summary

Introduction Prostate cancer (PCa) is a heterogeneous disease, with indolent and aggressive forms. The traditional elements used for risk stratification and management of PCa patients include: Clinical H&P and digital rectal exam (DRE) Prostate-specific antigen (PSA) test Gleason results from 10-12 core extended sextant biopsy

TRUS: The Standard of Care Transrectal ultrasound (TRUS) guided biopsy is standard of care for the diagnosis and surveillance of prostate cancer. Benefits: Established procedure Can be performed in the office setting Limitations: TRUS biopsies may (over)detect indolent PCa Significant Gleason understaging Undersampling of anterior gland, transition zone

mpmri: Best Imaging Test Prostate multiparametric magnetic resonance imaging (mpmri) is the most accurate imaging method for the detection and staging of PCa Initial use was for staging PCa patients Increasing role in evaluating patients with suspicion of PCa, planning biopsy, etc. Why not combine mpmri and TRUS?

MRI-TRUS Fusion Biopsy Pre Biopsy Lesion Identification Prostate Segmentation Lesion Volume of Interest Adapted from Costa DN, et. al. MR Imaging Transrectal US Fusion for Targeted Prostate Biopsies: Implications for Diagnosis and Clinical Management. Radiographics 2015 35(3) 696-708.

MRI-TRUS Fusion Biopsy Biopsy Procedure Prostate Segmentation Lesion VOI Projection Biopsy Mapping Adapted from Costa DN, et. al. MR Imaging Transrectal US Fusion for Targeted Prostate Biopsies: Implications for Diagnosis and Clinical Management. Radiographics 2015 35(3) 696-708.

MRI-TRUS Fusion Biopsy Post Biopsy MRI Benign TRUS Low Grade Gleason Mapping Clinically Significant Adapted from Costa DN, et. al. MR Imaging Transrectal US Fusion for Targeted Prostate Biopsies: Implications for Diagnosis and Clinical Management. Radiographics 2015 35(3) 696-708.

Potential Role of MRI-US Biopsy Incorporation in Current Risk Stratification Biopsy naïve patients? Standard biopsy negative patients? Specific Patient Groups Role in active surveillance? Focal therapies? Role in previously treated disease?

MRI-US Fusion Biopsy Results MRI-US fusion targeted biopsy data suggest potential improvements over standard biopsy Targeted approach detects more higher grade PCa over standard biopsy alone (32%) Targeted approach detects more clinically significant (Gleason 4+3) disease (67%) and missed lower grade (Gleason 3+4), potentially indolent disease (36%). Standard biopsy also led to upgrading (26%) but detected less clinically significant disease (only 8% Gleason 4+3). *Siddiqui MM., et. al. Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy. Eur Urol 2013 64(5) 713-19.

MRI-US Fusion Biopsy Results Recent systematic review reveals similar findings 15 studies with >2000 patients Median detection rate for clinically significant disease in standard biopsy was 23.6% (range: 4.8-52%) Median detection rate in targeted biopsy was 33.3% (range: 13.2-50%). Clinically significant was variably defined. *Valerio MM, et. al., Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review. Eur Urol 2015 68(1) 8-19.

Why Do Targeted Biopsies Fail? 13.5% (135/1003) of studied patients upgraded on systemic vs targeted biopsies Identified predictors of upgrading on systemic vs targeted biopsies include: Lower PSA (p<0.001) Larger gland size on MRI (p<0.001) Lower number of targeted cores (p=0.001) *Muthigi A, et. al. Missing the Mark: Prostate Cancer Upgrading by Systematic Biopsy over Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Biopsy. J Urol 2017 197(2) 327-334.

Why do Targeted Biopsies Fail? Several main reasons identified for undergrading of disease: mpmri reader oversight MRI Related mpmri invisible disease Tumor heterogeneity Biopsy technique error Biopsy Related *Muthigi A, et. al. Missing the Mark: Prostate Cancer Upgrading by Systematic Biopsy over Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Biopsy. J Urol 2017 197(2) 327-334.

Role in Active Surveillance Targeted biopsies may be superior for detecting Gleason upgrading in AS cohorts 166 patients undergoing AS with 2 or more bx ü Mean follow-up of 25.5 months Progression identified in 29.5% of patients ü 44.9% identified on targeted biopsy alone ü Fusion biopsy (targeted + systematic) found 26% more cases of progression than systematic alone Sole predictor of upgrading was mpmri findings ü 81% NPV; 35% PPV; 77.6% Sens; 40.5% Spec *Frye TP, et. al., Magnetic Resonance Imaging-Transrectal Ultrasound Guided Fusion Biopsy to Detect Progression in Patients with Existing Lesions on Active Surveillance for Low and Intermediate Risk Prostate Cancer J Urol 2017 197(3 Pt 1) 640-646.

Role in Active Surveillance Others have reported more positive results 259 patients undergoing AS ü 196 Gleason 6(3+3); 63 Gleason 7(3+4) Surveilled up to 4 yrs with 33 patients progressing ü 97% of Gleason upgrading occurred at targeted sites Predictors of upgrading included ü PSAD 0.15 ng/ml/cc ü mpmri lesion score of 5 ü Gleason 3+4 disease; 4.65x more likely than 3+3 *Nassiri, et. al., Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer J Urol 2017 197(3 Pt 1) 632-639.

Role in Focal Treatments It has been argued that MRI-US fusionguided biopsy the modality of choice for selecting patients for focal therapy*. BUT it is still imperfect # 454 pts with MR-US biopsy proven PCa 175 eligible for focal therapy (NCCN intermediate) 64 proceeded to prostatectomy 75% concordance for eligibility *Gordetsky J, et. al., Pathological Findings in Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy: Relation to Prostate Cancer Focal Therapy Urology 2017 105:18-23. # Nassiri N, et. al., Focal Therapy Eligibility Determined by Magnetic Resonance Imaging/Ultrasound Fusion Biopsy J Urol 2017 (in press)

Role in Post-treatment Prostates Little available data for assessment. Unclear even what mpmri sequences are needed. However, small studies have shown benefit in cases of recurrence after RP *Muller BG, et. al., Multiparametric magnetic resonance imaging-transrectal ultrasound fusionassisted biopsy for the diagnosis of local recurrence after radical prostatectomy. Urol Oncol 2015 33(10):425.e1-e6.

Limitations of MRI-US Biopsy Limitations of the Fusion Technology Expensive Learning curve Limitations Specific to mpmri The Radiologists Ongoing questions regarding acquisition protocols and scoring

Limitations Specific to mpmri Recent study compared initial and second opinion reads on outside mpmris for patients presenting to tertiary center for transperineal MR-US fusion biopsies Specialist tertiary reads had a higher NPV ü NPV for Gleason 7(3+4) or higher: 97% vs 84% (p=0.039) Tertiary reads more often read as negative ü41% vs 20% (p<0.001) *Hansen NL, et. al. Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy. Eur Radiol 2017 27(6) 2259-63.

Limitations Specific to mpmri Recent study compared initial and second opinion reads on outside mpmris for patients presenting to tertiary center for transperineal MR-US fusion biopsies Specialist tertiary reads had a higher NPV ü NPV for Gleason 7(3+4) or higher: 97% vs 84% (p=0.039) Tertiary reads more often read as negative ü41% vs 20% (p<0.001) *Hansen NL, et. al. Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy. Eur Radiol 2017 27(6) 2259-63.

Limitations Specific to mpmri Recent switch from PI-RADS v1 to v2 Continued ongoing debate regarding need for contrast Head to head comparison shows high agreement but differing AUC based on zone* üpi-rads v2 higher AUC in TZ üpi-rads v1 higher AUC in PZ *Polanec S, et. al. Head-to-head comparison of PI-RADS v2 and PI-RADS v1 Eur J Radiol 2016 85(6): 1125-31.

Summary Increasing evidence of improved patient stratification with MR-US fusion biopsy. Increasing supportive evidence for role in AS cohorts. May be best method for selecting patients for focal treatments and evaluating post treatment recurrence

Selected References 1. Siddiqui MM., et. al. Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy. Eur Urol 2013 64(5) 713-19. 2. Valerio MM, et. al., Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review. Eur Urol 2015 68(1) 8-19. 3. Costa DN, et. al. MR Imaging Transrectal US Fusion for Targeted Prostate Biopsies: Implications for Diagnosis and Clinical Management. Radiographics 2015 35(3) 696-708. 4. Sonn GA, Margolis DJ, Marks LS. Target Detection: Magnetic Resonance Imaging-Ultrasound Fusion-Guided Prostate Biopsy. Urol Oncol 2014 32(6) 903-11. 5. Muthigi A, et. al. Missing the Mark: Prostate Cancer Upgrading by Systematic Biopsy over Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Biopsy. J Urol 2017 197(2) 327-334.