Anatomic Imaging of Prostate Cancer

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Masoom Haider, MD, FRCP(C) Professor of Radiology, University of Toronto Clinician Scientist, Ontario Institute of Cancer Research Senior Scientist, Sunnybrook Research Institute Chief, Dept of Medical Imaging Sunnybrook Health Sciences Centre masoom.haider@sunnybrook.ca Anatomic Imaging of Prostate Cancer

Disclosure(s) Masoom Haider I have no financial relationships with commercial interests to disclose relevant to this presentation Consultant Bayer Advisory Board Participant Siemens 2

Local Staging Incremental Diagnostic Value - MRI Base Model PSA & clinical stage Gleason max % & sum of core PNI Wang et al Radiology 2004 n=344 216/344 spectroscopy MRI + base model better than clinical + biopsy p<0.02 3

Staging n MRI Partin Partin+MRI T1/2 <=G6 PSA<10 T1/2 G7 PSA 10-20 T3/4 >G7 PSA>20 Wang et al Radiology 2006 4

5

6 G4+3, 64yo PSA 7.63 DRE neg

Gleason 9 DRE +, PSA 4.5 Radiation Gleason 8 DRE -, PSA 3.7 Nerve sparing L

Nodes Sens ~40% Spec ~80% No difference MRI vs CT WB-DWI and Choline PET/CT Extraprostatic Metastases Complementary Choline more sensitive (97% vs 45%), specificity (58% vs 64%) Small studies (n=46) 8

Guidelines 1. mpmri use for pre-treatment local staging of prostate cancer is a reasonable option for assessment of extraprostatic extension (EPE) in intermediate- and high-risk patients being considered for radical therapy if knowledge of EPE will alter management 2. Centres using mpmri for local staging must have a quality assurance program in place to measure diagnostic performance of mpmri. 9

Cancer Localization The Sampling Problem 10

JAMA 2015 n = 1003 Addressing the Sampling Problem In men (mostly with a prior negative systematic biopsy) MR/ultrasound fusion biopsy, c/w systematic biopsy had increased detection of Gleason >=4+3, (+30%) and decreased detection of low-risk prostate cancer (-17%) Prostatectomy cohort Sens 77% vs 53% Spec 68 vs 66% (Gleason 3+4 in >20% of prostate) 11 Siddiqui MM, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama. Jan 27 2015;313(4):390-7.

PROMIS Lancet 2017 Level 1b Evidence N=576/740 - No prior biopsy and suspicion of prostate cancer Transperineal mapping biopsy as reference standard Systematic TRUS biopsy and mpmri performed Upto 27% of primary biopsy avoided and 5% fewer clinically insignificant cancers detected Upto 18% more clinically significant cancers might be dertected with guided biopsy 12

PROMIS Study 13

Standardization Pi-Rads v2.0 5 point scale An Imaging Biomarker 14

T2 axial T2 coronal T2 sagittal DWI b1600 (b1400-2000) ADC (W/L 1400 1400) DCE

64yo PSA 10 PSAD 0.23 ADC 587 Pi-Rads 4 Gleason 4+3 75% perineural invasion

73yo PSA 2 to 4ng/ml over 3 years ADC 865 Pi-Rads 4/5 Gleason 3+4 at Biopsy/Prostatectomy

58yo PSA 4.42 PSAD 0.21 BRCA 1 carrier ADC 551 Pi-Rads 4 Gleason 4+3 75% of core / RadP Gleason 3+4 - bilateral

CCO Ontario Guidelines 27-2 In patients who had a prior negative TRUS-guided systematic biopsy and demonstrate a growing risk of having clinically significant prostate cancer mpmri followed by targeted biopsy may be considered to help in detecting more clinically significant prostate cancer patients compared with repeated TRUS-guided systematic biopsy. 19

CCO Ontario Guidelines 27-2 In patients with an elevated risk of clinically significant prostate cancer (according to PSA level and/or nomograms) who are biopsy-naïve: mpmri followed by targeted biopsy (biopsy directed at cancer-suspicious foci detected with MPMRI) should not be considered the standard of care. Data from future research studies are essential 20

21 PSA 13.00 +29mo PSA 25.93 Gleason 4+4 90% of core pt3a, N0 PRECISE Progression Scale Likert 5

Guidelines mpmri in AS ACR Appropriateness Criteria 2013 = 6 (May be appropriate (2013) Cancer Care Ontario (2015) mpmri considered when a patient s clinical findings are discordant with the pathologic findings NCCN (2016) Consider mpmri if anterior and/or aggressive cancer is expected when PSA increases and systematic biopsies are negative NICE (2014) At enrollment or if event suggesting progression 22

ADC Correlates with Gleason Score Hambrock T et al. Radiology 2011 23

24 Radiomics A Convoluted Genesis of IB Motivated by spatial/temporal/biologic heterogeneity of cancer and non-invasiveness of imaging 1. Feature Extraction (Radiologists + Image Analysis Team) 2. Biologic Validation (Radiogenomic) Analysis Correlation with other omic profiles cv 3. Clinical Utility - Diagnostic/Predictive/Prognostic Analysis Gleason Score/Time to Intervention/Risk Nomograms 24

mpmri Feature Analysis T2 Feature Group 1 Balancing Data ADC Contiguous Features ADC Feature Group 2 Feature Reduction Integrated Feature Set 25 CDI Feature Extraction Feature Group 3

Pearson s correlation Imaging features and 65 genes from commercially available prostate cancer classifiers Stoyanova, R. et al. Association of multiparametric MRI quantitative imaging features with prostate cancer gene expression in MRI-targeted prostate biopsies. Oncotarget (2016). N=6 26

Gene ontology (GO) Several fluid transport (yellow bar) and adhesion (green bar) processes are associated with the ROI radiomic ADC features. Normal appearing tissue regions may contribute to tumor phenotype or vice versa 27

ADC vs Radiomics for Prediction of Clinically Significant Disease ROC AUC CAD: 0.84 ADC: 0.70 ADC CAD 28

29