11/10/2015. Prostate cancer in the U.S. Multi-parametric MRI of Prostate Diagnosis and Treatment Planning. NIH estimates for 2015.

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Philomena Nicholson
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Associate Professor of Radiology Director, Genitourinary Radiology Indiana University School of Medicine Department of Radiology and Clinical Sciences

Second leading cause of death among in men NIH estimates for 2015 Mortality 5 year survival rate is 98.

1 Multi-parametric MRI of Prostate Diagnosis and Treatment Planning Temel Tirkes, M.D. Associate Professor of Radiology Director, Genitourinary Radiology Indiana University School of Medicine Department of Radiology and Clinical Sciences Prostate cancer in the U.S. 14% of all men in the US will be diagnosed with prostate cancer. Second leading cause of death among in men NIH estimates for 2015 Mortality 5 year survival rate is 98.9% for localized disease New Cases of All New Cancers Number of Deaths Of All Deaths Percent of cases by stage 5 year survival by stage 220, % 27, % Source: CDC Prostate Cancer Risk Factors Diagnosis of Prostate Cancer Age: > 60% of men > 65 Sex: more comm0n in African-American men Life style: obesity, high fat diet, lack of exercise Digital rectal exam PSA level Transrectal ultrasound MRI PSA level Cancer Normal < 4 ng/ml 15 % Suspicious 4 10 ng/ml 25 % Elevated > 10 ng/ml 67 % 1

Missed TRUS biopsy Over sampled False elevated Gleason score Prostate Anatomy The

T2-weighted images Missed Anterior tumor Missed Under sampled False low Gleason

com/ AFT= anterior f ibromuscular tissue, CZ=central zone, PZ=peripheral zone, TZ=

bundle, U=urethra Normal Staging of Prostate Cancer Gleason score Terminology SV

d 7, 8, 9 and 10 Poorly differentiate d mid apex sagittal Modified from F. D.

Gleason Grading System and Scoring Prostate MRI Gleason score; the first number is

(primary) + 3 (secondary) The Gleason patterns Pattern 2 = well formed glands

Moderately differentiated carcinoma Pattern 4 = invading surrounding tissues,

carcinoma From Modern pathology, (2005-18, 1022-1026) MR is the recommended

MRI helps surgeon s pre-operative plan; improve the surgical outcome by maximizing

2 Missed TRUS biopsy Over sampled False elevated Gleason score Prostate Anatomy The zonal anatomy of the prostate gland is best depicted on high-resolution T2-weighted images Missed Anterior tumor Missed Under sampled False low Gleason score AFT= anterior f ibromuscular tissue, CZ=central zone, PZ=peripheral zone, TZ= Transitional zone PUT=periurethral tissue, ED=Ejaculatory duct, NVB=neurovascular bundle, U=urethra Normal Staging of Prostate Cancer Gleason score Terminology SV base mid base/mid 2, 3 and 4 Well differentiate d 5 and 6 Moderately differentiate d 7, 8, 9 and 10 Poorly differentiate d mid apex sagittal Modified from F. D. Gleason, M.D. Filip G. Claus; et al; RadioGraphics 2004, 24, S167-S180. Gleason Grading System and Scoring Prostate MRI Gleason score; the first number is primary grade and the second number is the secondary grade Ex/ Gleason 5 = 2 (primary) + 3 (secondary) The Gleason patterns Pattern 2 = well formed glands Moderately differentiated carcinoma Pattern 3 = invasive and infiltrative Moderately differentiated carcinoma Pattern 4 = invading surrounding tissues, poorly differentiated tumor Pattern 5 = no recognizable glands, Anaplastic carcinoma From Modern pathology, ( , ) MR is the recommended imaging modality for preoperative staging of prostate cancer. MRI helps surgeon s pre-operative plan; improve the surgical outcome by maximizing the preservation of peri-prostatic nerve and vessels (responsible for urinary and sexual function). minimizing the risk of positive surgical margins. mark the lesions for targeted biopsies or treatment. 2

Multi-parametric MRI Protocol T1-weighted images (Axial) T2-weighted images (Axial, Sagittal and Coronal) T2-weigthed images with fat

External pelvic phase array coil Endorectal coil ER increases the SNR 3T with ER coil > w/out coil 1.

3 days TNM Staging Key Image Sequences for Tumor T2 weighted DWI with ADC map Dynamic Contrast Enhanced (DCE) images TNM classification revised

signal on T2 T2-weighted images T2 signal has limited value in CZ and TZ in patients with BPH T2 only 62% 69% 64% 76% T2 + DWI + DCE 69% 94%

3 Multi-parametric MRI Protocol T1-weighted images (Axial) T2-weighted images (Axial, Sagittal and Coronal) T2-weigthed images with fat suppression (Axial) Diffusion weighted images (DWI) with ADC map (Axial) Dynamic contrast enhanced images (DCE) Multi-parametric MRI Protocol External pelvic phase array coil Endorectal coil ER increases the SNR 3T with ER coil > w/out coil 1.5T with ER coil Glucagon 1 mg IV to suppress the bowel peristalsis At least 8 weeks time from the prostate biopsy +/- avoid sexual activity for 3 days TNM Staging Key Image Sequences for Tumor T2 weighted DWI with ADC map Dynamic Contrast Enhanced (DCE) images TNM classification revised by American Joint Committee on Cancer, 2002 Combining Imaging Techniques Multi-parametric MRI Sensitivity Specificity Accuracy PPV Tumor is low signal on T2 T2-weighted images T2 signal has limited value in CZ and TZ in patients with BPH T2 only 62% 69% 64% 76% T2 + DWI + DCE 69% 94% 79% 95% Yoshizako et al (2008) Acta Radiol 49: Other causes fror low signal in PZ Inflammation prostatitis Hemorrhage post biopsy blood Post-radiation therapy Hormone deprivation (therapy) 3

4 Post-biopsy hemorrhage Post-biopsy hemorrhage T1 weighted images detect post-biopsy hemorrhage Hemorrhage decreases signal on T2 and mimics tumor At least 8 weeks required to clear hemorrhage before MR. Post hormonal therapy Extra-capsular extension Neurovascular bundle involvement Stage T3 Decreased T2 signal of peripheral zone Bulge Invasion Extra-capsular extension Seminal vesicle invasion StageT3b Extra-capsular extension Bladder wall invasion Stage T4 4

Extra-capsular extension Rectal wall invasion Stage T4 Extra-capsular

the lower pelvis Diffusion-weighted Imaging (DWI) Diffusion-weighted

DWI adds specificity to T2 images and estimates aggressiveness of the

Cancer is low signal on ADC map Combination of T2 and DWI improves

histologic grade Dynamic Contrast Enhanced (DCE-MR) Tumoral vasculature

permeability surface area, and interstitial volume are much greater in

5 Extra-capsular extension Rectal wall invasion Stage T4 Extra-capsular extension Lymph node metastasis Stage N1 R R MR only shows the LNs in the lower pelvis Diffusion-weighted Imaging (DWI) Diffusion-weighted Imaging Cancer generally restricts movement of water molecules due to higher cell densities. DWI technique measures the free motion of the water molecules. DWI adds specificity to T2 images and estimates aggressiveness of the tumor. Cancer is low signal on ADC map Combination of T2 and DWI improves accuracy Diffusion-weighted Imaging ADC values correlate with histologic grade Dynamic Contrast Enhanced (DCE-MR) Tumoral vasculature is disorganized, irregular and fragile Mean transit time, blood flow, permeability surface area, and interstitial volume are much greater in cancerous tissues than in normal tissues Rapid enhancement rapid washout seen with both cancer and BPH Nature Medicine 7, (2001) doi: /nm Thomas Hambrock; et al; Radiology 2011, 259,

Dynamic Contrast Enhanced (DCE-MR) Combining DCE-MRI with ADC helps to distinguish cancer from SH.

ADC + K-trans: 57%, Specificity: 90% Detect clinically important prostate cancer in 93% of cases. Hara et al.

Transendothelial transport of contrast medium from vascular compartment to the tumor interstitium.

reverse transport parameter of contrast medium back into the vascular space.

6 Dynamic Contrast Enhanced (DCE-MR) Combining DCE-MRI with ADC helps to distinguish cancer from SH. Radiology 2010, 257, Aytekin Oto. Et al. ADC + K-trans: 57%, Specificity: 90% Detect clinically important prostate cancer in 93% of cases. Hara et al. Prostate 2005: 62: What is K-trans? Transendothelial transport of contrast medium from vascular compartment to the tumor interstitium. Wash-in or enhancement What is K-ep? reverse transport parameter of contrast medium back into the vascular space. washout Dynamic Contrast Enhanced (DCE-MR) Tumors demonstrate rapid wash-in (k-trans) and rapid washout (k-ep) Wash-in k-trans map Wash-out k-ep map Central Gland Cancer Central Gland Cancer 30% of prostate cancers arise from the central gland T2 K-trans map Radiology 2010, 257, Aytekin Oto. et al. Radiology 2010, 257, Aytekin Oto. et al. 6

gland can be difficult due to histologic

Organized chaos SH is main cause of false

map (mildly hypointense) (Not decreased)

Hyperplasia Benign Glandular Hyperplasia

7 Central Gland Cancer Benign Prosthetic Hyperplasia Detection of cancer in central gland can be difficult due to histologic heterogeneity in BPH Glandular hyperplasia (GH) is easy to distinguish Stromal hyperplasia (SH) mimics Prostate cancer: T2 hypointense H&E stain K-trans map MR features Cancer SH GH Hypointense T2 Signal Hyperintense T2 Shape Amorphous Amorphous/Oval Round/Oval Capsule Benign Prostatic Hyperplasia Benign Stromal Hyperplasia BPH Organized chaos SH is main cause of false negative TRUS biopsies T2 ADC map K-trans map (mildly hypointense) (Not decreased) (diffuse abnormality) Benign Stromal Hyperplasia Benign Glandular Hyperplasia Ca SH GH GH GH GH Ca Ca Ca T2 ADC map K-trans map (unlike cancer) (unlike cancer) (unlike cancer) 7

PI-RADS (Prostate Imaging Reporting and Data System) Standard

and treatment of prostate cancer Prostate Imaging Reporting and Data

significant cancer highly unlikely) Low (clinically significant

(clinically significant cancer equivocal) Probably biopsy PIRADS 4

high (clinically significant cancer is highly likely) Biopsy Prior

8 PI-RADS (Prostate Imaging Reporting and Data System) Standard reporting system based on suspicion score To improve early diagnosis and treatment of prostate cancer Prostate Imaging Reporting and Data System (PI-RADS 2) PI-RADS Categories Very low (clinically significant cancer highly unlikely) Low (clinically significant cancer unlikely) No recommendations follow-up PIRADS 3 Intermediate (clinically significant cancer equivocal) Probably biopsy PIRADS 4 High (clinically significant cancer is likely) Biopsy PIRADS 5 Very high (clinically significant cancer is highly likely) Biopsy Prior TRUS bx negative Prostate Fusion biopsy ADC = 587 Prostate Fusion biopsy Prostate Fusion biopsy 8

Prostate Fusion biopsy Treatment response by DCE-MRI In

yield additional qualitative and quantitative information

American Journal of Roentgenology. 2011;197: 907-915.

radiation tx 2 months after radx Red= abnormal k-trans Blue=

T2 low signal on PZ No wash-in area on DCE Russell et al.

the lower levels of citrate and higher levels of choline of

Provides information about lesion aggressiveness, but does

9 Prostate Fusion biopsy Treatment response by DCE-MRI In conjunction with serial serum PSA measurement, DCE-MRI can yield additional qualitative and quantitative information about tumor response to therapy. Russell et al. American Journal of Roentgenology. 2011;197: Treatment response by DCE-MRI Post Hormonal Treatment Before radiation tx 2 months after radx Red= abnormal k-trans Blue= normal k-trans 6 months after radx 12 months after Decreased T2 low signal on PZ No wash-in area on DCE Russell et al. American Journal of Roentgenology. 2011;197: Recurrence status post prostatectomy MRSI is able to show the lower levels of citrate and higher levels of choline of prostate cancer. Provides information about lesion aggressiveness, but does not give staging information owing to its poor spatial resolution. Thus, MRSI is a valid tool for detecting cancer recurrence and monitoring therapy response. Not routinely used. MR Spectroscopy Normal Cancer 9

10 MR vs Choline PET scan MR vs Choline PET scan MRI is superior to Choline PET in detection of local recurrence in postprostatectomy patients. Choline PET scan is limited in patients with low PSA values. Kazuhiro Kitajima et al. J Nucl Med 2014; 55:1 10 PSA 6 ng/dl PSA 1.3 ng/dl Kazuhiro Kitajima et al. J Nucl Med 2014; 55:1 10 MR vs Choline PET scan Prostatectomy Choline PET scan has excellent sensitivity in detecting metastatic LNs. Kazuhiro Kitajima et al. J Nucl Med 2014; 55:1 10 Focal treatment options - HIFU Focal treatment options - HIFU TULSA procedure, Profound Medical Corp HIFU (High Intensity Focused Ultrasound) ablation therapy 10

11 Future Search for more accurate diagnostic and localized treatment options brought greater use for prostate MRI to guide these sophisticated techniques. Multi-parametric MRI of Prostate Diagnosis and Treatment Planning Temel Tirkes M.D. Associate Professor of Radiology Director, Genitourinary Radiology Indiana University School of Medicine Department of Radiology and Clinical Sciences 11

Essentials of Clinical MR, 2 nd edition. 73. Urinary Bladder and Male Pelvis

Essentials of Clinical MR, 2 nd edition. 73. Urinary Bladder and Male Pelvis 73. Urinary Bladder and Male Pelvis Urinary bladder carcinoma is best locally staged with MRI. It is important however to note that a thickened wall (> 5 mm) is a non-specific finding seen in an underfilled