Utilizing MRI in Prostate Cancer Diagnosis and Fusion Biopsy Ari Goldberg MD,PhD Dept. Radiology Loyola University Medical Center

Prostate CA ► ~1 in 7 men diagnosed with prostate CA at some point in lifetime ► ~241,000 new cases in 2015 ► Mortality expected to be ~28,000 in 2016 in the US ► Traditional diagnosis:  PSA, DRE  TRUS

Staging  Gleason ► Combination of primary and secondary pathologic morphology, each on 1-5 scale.  5 = poorly-differentiated  Ex: = 7 = Dominant pattern of poorly organized cells with pockets of well-organized gland.  Low-Risk: PSA < 10, Gleason < 6  Medium-Risk: PSA 10-20, Gleason 7  High-Risk: PSA>20, Gleason > 7  Imaging ► CT abdomen/pelvis ► MRI ► Nuclear studies (PET, bonescan)

Biopsy  TRUS (12 core) ► ~1.2 Million annually ► ~0.04% of the gland is sampled  NPV? ► Cancer detection rates of 27-40% ► Incorrect characterization  PPV? Non-clinically-significant cancer  Prostate Cancer is only solid-organ tumor currently diagnosed without routine imaging

Prostate MRI ► Advantages of MRI:  Superior tissue characterization ► Normal vs. abnormal tissue ► Gland architecture  Non-invasive  No ionizing radiation  Visualization of gland within the surrounding anatomy  Regional evaluation for metastatic disease.

Traditional prostate MR indications ► Staging for biopsy-proven CA ► Extent within gland  Location  Identify multifocal disease/upstage ► Extra-glandular spread  ECE  Seminal Vesicle  Fat  Bones  Nodes  MRI has altered care to or from nerve-sparing between ~25% of time in multiple studies (including internal LUMC data)

MP vs ER ► ER coil  Increased SNR, spatial resolution  Spectroscopy  Decreased patient motion  Disadvantages ► Patient discomfort ► Posterior artifact ► MP  3T vs 1.5T ► Increased SNR, spatial resolution ► Increased temporal resolution ► Increased field inhomogeneity ► Recent spectroscopy ► Overall: MP for staging, ER for diagnosis

ER Coil Workflow ► Patient – light diet preceding day ► Enema at home ► IV access ► Minimal rectal exam followed by coil insertion with xylocaine ► Inflation of balloon  Barium ► Readjustment common, ~5 mins

Standard Prostate MR

T2W T1W

Extracapsular Extension

Advanced Disease

What are other MR indications? ► Diagnosis  +PSA/-TRUS  +PSA  AS ► Post-surgical surveillance  Recurrent tissue  Nodes, bones

Multi-parametric MRI for Diagnosis ► Sequences/parameters used to detect and characterize lesions:  T1  T2  Diffusion  Dynamic Contrast enhanced ► Significantly more specific

Advanced sequences ► Dynamic Contrast Enhanced (DCE) T1 imaging  Angiogenesis  Rapid wash in and washout  Better at 3T (temporal and spatial resolution) ► Diffusion Imaging  Increased diffusion restriction in tightly- packed malignant cells ► 3D voxel Spectroscopy  Malignant cells have increased choline/citrate  Chemical shift imaging

Suspicious MRI characteristics ► Low T2  Peripheral zone  Central “charcoal” appearance ► Abnormal diffusion  Can measure quantitatively  High B-field best ► Fast wash-in/wash-out kinetics  Post-processing generates wash-in/out curves of voxel signal vs. time.

DCE Very sensitive, not very specific

T2+Diffusion

Interpretation ► PIRADS (Prostate Imaging Reporting And Data System) ► PIRADS II  1-5 ► Peripheral zone and Transitional zone get separate scores. Peripheral weights DWI and Transitional weights T2:  3=Indeterminate  4=Probable  5=Highly likely. More focal abnormal signal and/or size > 1.5 cm and/or capsular involvement. ► DCE only plays minor role  Studies have found that more focal and more quantitatively abnormal diffusion and post-contrast signal correlates with increased Gleason score but is not yet quantitative. ► Accuracy: mpMRI reduces the detection of low-risk PCa and reduces the number of men requiring biopsy, while improving the overall rate of detection of intermediate/high-risk PCa ► Accuracy: mpMRI reduces the detection of low-risk PCa and reduces the number of men requiring biopsy, while improving the overall rate of detection of intermediate/high-risk PCa European Urology, Volume 66 Issue 1, July 2014, Pages 22-29Volume 66 Issue 1

MRI for diagnosis? ► Abnormal signal not yet sufficient ► Biopsy still required ► So, does it make sense to do diagnostic MRI on patient with +PSA? Or +PSA/-TRUS?  Result of suspicious signal focus not helpful without ability to localize for biopsy.

In-Gantry MRI ► Technically challenging ► Less comfortable ► COSTLY!  Avg time ~1.5 hr  Scanner time premium  Access ► Low Urologist acceptance

MRI-US fusion-guided biopsy ► Generate MRI prostate “mold” from MRI images ► Tumor depicted within the virtual mold

MRI-US fusion-guided biopsy ► Virtual mold with in-situ lesion is transferred to Fusion- biopsy system server connected to US machine. ► Operator uses TRUS probe to sweep prostate and generate US-based prostate volume. ► The two volumes are fused

MRI-US fusion-guided biopsy

MRI/TRUS TRUS probe has a sensor which lets the computer know its position TRUS probe can then be guided to the lesion for precise throws

NIH experience ► Published in JAMA 1/27/15 ► 1003 patients from 2007 to 2013  All received MRI and subsequent guided-Bx when indicated  All received standard 12-core Bx  Whole-gland pathology available in 170 patients ► MR-guided Bx yielded:  30% greater high-risk cancers  17% fewer low-risk cancers  Overall significantly fewer false-negatives for >low-risk disease ► Multiple studies in past 2 years support these numbers

LIJ/NorthShore MRI/US experience

Their Conclusions ► Degree of MR suspicion correlates directly with incidence of cancer on pathology.  ~90% of patients with high-suspicion (5) on MR are diagnosed with cancer on biopsy. ► 55% over all cancer detection rate  20-40% increased detection of Gleason > 7  Excludes low-risk cancers which are missed by ~15-20% ► 35-45% cancer detection in patients with previous negative 12-core ► 20% upstage in patients on AS

Indications for Prostate MRI + fusion biopsy ► +PSA,- Negative biopsy  Significant part of LUMC volume  > 50 cases of (+) disease in setting of multiple-negative and saturation-negative, consistent with literature ► AS  Low risk disease = low-grade and localized  Yearly monitoring (biopsy)  Establish baseline  Yearly MRI +/- fusion ► Localize new/growing lesion for biopsy ► Elevated PSA or abnormal DRE  Thus far covered by CMS and private insurers

Negative TRUS but….

LUMC data, % Ca detected

Things to Think About ► Imaging time ~45 mins  1 hour slot ► MRI Prostate = MRI pelvis w/wo + 3D code ► GFR > 30  OK to do w/o contrast ► Who puts in ER coil? ► System for image transfer ► TAT ► OK to do w/o ER coil ► Patient education

So, Evolving utilization ► MRI + Fusion Bx as diagnosis ► AS  Follow with MRI? MRI + fusion-biopsy? ► Role in focal treatment monitoring?

Who will perform Biopsies? ► Radiologists at LUMC trained in Fusion Bx  But we don’t do them ► Urologists have long history of in-office US biopsy ► Fusion Bx platforms being purchased by most Urology groups in the Chicago area ► Urologists not interested in losing patients

A Rising Tide… ► Urologists with Fusion Bx US system mostly still need an MRI partner  Connect! ► Office talks ► Conferences ► Media (Youtube, ) ► Manage access – no detail too small ► Started LUMC program Jan 14  > 700 so far  Avg of 3 per day at this time ► Growth enabled Research Fellow