MRI/US Fusion for Prostate Cancer

Kenneth L. Gage MD, PhD Assistant Member

Department of Diagnostic Imaging and Interventional Radiology

2nd Annual New Frontiers in Urologic Oncology Marriott Waterside, Tampa, FL

September 12, 2015

Disclosure

No financial disclosures or potential conflicts of interest

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

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Number of New Prostate Cancer Cases and Deaths per 100K People

New Cases Deaths

Howlader N, et. al. (eds). SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2012/, based on November 2014 SEER data submission, posted to the SEER web site, April 2015.

Why MRI-US Fusion? Transrectal ultrasound (TRUS) guided biopsy is standard of care for the diagnosis of prostate cancer.

Limitations: • TRUS biopsies may (over)detect indolent PCa • Significant Gleason understaging • Undersampling of anterior gland, transition zone

Benefits: • Established procedure • Can be performed in the office setting

Why MRI-US Fusion? Prostate magnetic resonance imaging (MRI) is the most accurate imaging method for the detection and staging of prostate cancer. • Initial use was for staging PCa patients • Increasing role in evaluating patients with

suspicion of PCa, planning biopsy, etc.

Limitations: • Learning curve, operator dependent • Expensive

MRI-TRUS Fusion Biopsy Pre Biopsy

Prostate Segmentation

Lesion Identification

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.

Prostate Segmentation

Lesion VOI Projection

Biopsy Mapping

MRI-TRUS Fusion Biopsy Biopsy Procedure

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 Gleason Mapping

Benign Low Grade Clinically Significant

MRI-TRUS Fusion Biopsy Post Biopsy

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-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.

Role of MRI-US Fusion Biopsy NCCN Guidelines* suggest a role for MRI • Post 2 negative TRUS biopsies • In high risk pts with negative biopsy results

Challenges include: • Cost and availability • Heterogeneity of existing approaches, techniques • Impact upon pre-existing risk stratification

methods *Prostate Cancer Early Detection, Version 1.2014 NCCN Clinical Practice Guidelines in Oncology, http://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf, accessed April 2015.

Emerging 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?

On the Horizon Computer Aided Detection & Classification

MRI-US Fusion Biopsy starts with MRI • Changing classification schemes • Changing emphasis on MRI sequences Evolving computer aided detection and classification methods are poised to have a greater role in multiparametric prostate MRI.

Litjens GJ, et. al. Computer-extracted Features Can Distinguish Noncancerous Confounding Disease From Prostatic Adenocarcinoma at Multiparametric MR Imaging. Radiology 2015 (in press).

Over the Horizon Novel PET Imaging Agents

Next Generation PSMA Tracers • 18F-DCFPyL • 68Ga-HBED-CC

PET-MRI-US Fusion Biopsy • Fusion technology is straightforward • “Killer Application” for PET/MRI?

Szabo Z, et al. Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA) Targeted detection of Prostate Cancer. Mol Imaging Biol 2015 (in press) Afshar-Oromieh A, et. al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015 42(2): 197-209.

Summary

MRI-US fusion targeted biopsy data suggest potential improvements over standard biopsy. Specific role and patients are currently not well defined. Multisite trials are needed to help answer many of the remaining questions.

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. Prostate Cancer Early Detection, Version 1.2014 NCCN Clinical Practice Guidelines in Oncology, http://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf, accessed April 2015.

Questions?

Contact Information: Kenneth L. Gage, MD, PhD kenneth.gage@moffitt.org

Thank You