Prostate MRI Hamidreza Abdi, MD,FEBU Post Doctoral Fellow Vancouver Prostate Centre UBC Department of Urologic Sciences May-20144

Transcription

1 Prostate MRI Hamidreza Abdi, MD,FEBU Post Doctoral Fellow Vancouver Prostate Centre UBC Department of Urologic Sciences May-20144

2 Objectives: Detection of prostate cancer the need for better imaging What is multiparametric MRI? What is MRI guided biopsy? Clinical context for MRI evaluation of the prostate: a. Staging b. Prior negative biopsy c. Active Surveillance d. Before biopsy

3 Finding Prostate Cancer

4 Finding other cancers Breast mammography, ultrasound, MRI Kidney CT-scan, ultrasound Colon colonoscopy Lung chest x-ray or CT Bladder - cystoscopy

5 Transrectal Ultrasound

6 TRUS a tool to guide needle

7 Determining extent of CaP Risk factors: PSA DRE Biopsy Gleason # cores extent of cores

8 Critical need for better imaging of the prostate Determine size and extent of prostate tumour after diagnosis Find tumour in patients with rising PSA despite prior negative biopsy Rule out more significant cancer in patients on active surveillance Find tumour in patient with high PSA BEFORE first biopsy

9 What is multiparametric MRI?

10 MRI Scanner Mid 1980s 3 T 2004

11 Endorectal coil 1989

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13 2005 Multiparametric MRI Standard series = T2 anatomic Diffusion-weighted imaging (DWI) functional Dynamic contrast enhancement (DCE) functional MR-spectroscopy (MRS) functional

14 T2-Weighted Imaging good for defining anatomy water (e.g. urine in bladder): white ( high signal intensity ) cancer: black ( low signal intensity ) BPH nodules heterogenous organized chaos difficult to distinguish cancer from BPH nodule without further sequences 1987

15 T2-Images Hoeks CM, et al. Radiology 2011;261: Puech P, et al. Radiology 2013;268:461-9.

16 Diffusion Weighted Imaging DWI assesses the ease of water movement (diffusion) between different tissue compartments reflects cell density and cell membrane integrity tumours show restricted diffusion Apparent Diffusion Coefficient (ADC) value is a measure of diffusion: <600 high level of suspicion >1000 intermediate level of suspicion low level of suspicion

17 Hoeks CM, et al. Radiology 2011;261:46-66.

18 Dynamic Contrast Enhancement (DCE) able to detect increased vascularity in cancer fast T1- weighted sequence before and after rapid injection of a bolus of contrast (gadolinium) prostate is highly vascular so that a simple comparison of pre and post- injection is not always diagnostic emphasis on dynamic how fast is contrast taken up into lesion? how fast does contrast wash out of lesion? Barentsz JO, et al. European Radiology 2012;22:

19 Barentsz JO, et al. European Radiology 2012;22:

20 MR Spectroscopy (MRS) MRS is used to measure metabolite concentrations within the prostate. Higher levels of choline and creatinine relative to citrate are characteristic of prostate cancer.

21 Ratio of choline to citrate predicts likelihood of cancer Hoeks CM, et al. Radiology 2011;261:46-66.

22 PIRADS Score Prostate imaging reporting and data system Score 1 = highly unlikely Score 2 = unlikely Score 3 = equivocal Score 4 = likely Score 5 = highly likely to have clinically significant prostate cancer

23 Differential Diagnosis bleeding in prostate after prior biopsy T1-weighted imaging can help distinguish wait 8 weeks after biopsy before doing MRI BPH nodule chronic or acute inflammation/prostatitis prostatic abscess

24 MRI Safety no ionizing radiation like a CT scan safe in pregnancy claustrophobia poses a challenge metallic objects are biggest limitation: dangerous: cochlear implants (ear), pacemakers take precautions: ferrous metal objects such as old gunshot fragments, surgical prostheses, aneurysm clips objects can get overheated and can move safe: titanium surgical clips, brachytherapy seeds

25 Quality control study done in appropriate scanner according to standard protocols study interpreted by qualified radiologist currently the biggest obstacles to routine use of MRI (more than cost and access)

26 MRI for Staging

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28 MRI for staging Tempany et al.1994

29 MRI Staging Is there EPE on RP if MRI says there is (PPV)? low risk 69% intermediate risk 90% high risk 89% Is EPE absent if the MRI says it is absent (NPV)? low risk 88% intermediate risk 57% high risk 38% 2013 Nov;190(5):

30 MRI after prior negative biopsy

31 Typical patient scenario 62 year old healthy male PSA 2.3 to 4.5 to 6.6 over 3 years prostate biopsy shows benign glands, mild chronic inflammation 6 months post biopsy PSA months post biopsy PSA 9.8 Now what????

32 Limitations of TRUS-biopsy Ukimura et al. 2013

33 Undersampling

34 Limitations of TRUS-biopsy under-sampling: 33% cancers missed on first biopsy under-estimation of Gleason grade: 33% of cases have higher Gleason on RP over-detection of insignificant cancer: 33% of cancer suitable for active surveillance Trans-Rectal Ultrasound

35 Back to our patient.. 62 year old healthy male PSA 2.3 to 4.5 to 6.6 over 3 years prostate biopsy shows benign glands, mild chronic inflammation 6 months post biopsy PSA months post biopsy PSA 9.8 Now what????

36 Rising PSA despite prior negative biopsy current practice: repeat biopsy consider biopsy of transition zone and anterior apex.. more cores evolving practice: multiparametric MRI identify lesion(s) biopsy specific lesion(s) with targeted biopsy

37 MRI-guided prostate biopsy 1. Cognitive physician doing biopsy is familiar with MRI findings and targets area of prostate where lesion should be with usual ultrasound guidance simple, quick and requires no additional equipment disadvantage: potential for human error 2. Direct or in-bore MRI-guided biopsy MRI to confirm biopsy needle localization labour-intensive, time-consuming and expensive usually only suspicious lesions are sampled

38 In bore MRI-guided biopsy UCLA-RADIOLOGY

39 MRI-guided prostate biopsy 3. Fusion biopsy: software used to register specific MRI locations with same location on transrectal 3D ultrasound pre-biopsy mpmri images then fused with the real-time ultrasound image suspicious lesion on MRI targeted specifically requires specific software and equipment limited by imperfect registration can be performed in minutes in outpatient setting under local anesthesia

40 Turkbey B, et al. Nature Reviews Urology 2009;6:

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42 Finding Prostate Cancer

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44 Prior negative biopsy 105 subjects with elevated PSA and prior negative biopsy fusion biopsy revealed CaP in 36/105 men (34%) 26 (72%) had clinically significant CaP 91% significant CaP in targeted cores compared to 54% in systematic cores 2014;65:

45 pooled analysis of men with an initial negative biopsy 328 of 479 (69%) had a suspicious MRI 229 of 328 (70%) had a positive biopsy 2013;63:

46 Vancouver Experience

47 Vancouver Experience 2010 to 2013 Vancouver General Hospital 2416 biopsies 283 men had prior negative biopsies MRI was obtained in 112 of 283 lesion (PIRADS score 3) was identified in 88 (79%) matching cohort of 86 patients who underwent 2 nd biopsy without MRI matched for PSA level, PSA density, prostate volume, and history of ASAP or HGPIN in previous biopsies

48 Vancouver Experience mean size (maximal diameter) of the largest lesion in 86 patients was 15.5 mm total of 164 lesions PIRADS 3 99 (60.4%) PIRADS 4 48 (29.2%) PIRADS 5 17 (10.4%) cognitive biopsy in 32 cases fusion biopsy in 54 cases

49 Vancouver Experience Biopsy result Target group (N = 86) Control group (N = 86) P value Any cancer detection 36 (42%) 19 (22%) Significant cancer (Gleason 7) 30 (35%) 14 (16%) MRI-guided biopsy detected 9 significant CaP that were missed on standard cores, and standard cores detected 6 significant CaP missed on targeted cores.

50 Vancouver Experience PIRADS Score Benign Any CaP Significant CaP 3 (n=46) 33 (72%) 13 (28%) 8 (17%) 4-5 (n=40) 17 (43%) 23 (57%) 22 (55%)

51 Variable OR 95% CI P value PSA ( ) 0.71 Lesion size on MRI 0.95 ( ) 0.35 Number of previous biopsies 2 > ( ) 0.09 PSA Velocity 0.75 ng/ml/yr >0.75 ng/ml/yr ( ) 0.97 PSA Density 0.15 ng/ ml 2 1 >0.15 ng/ ml ( ) PIRADS 3 > ( ) <0.001

52 PSA Density PSAD < 0.15 ng/ ml 2 PSAD >= 0.15 ng/ ml 2 Total PIRADS No CaP CaP scap No CaP CaP scap* / Total

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54 MRI after negative biopsy In patients with persistent concern for CaP despite a prior negative prostate biopsy, MRI improves the detection of CaP and scap. PSA density can further stratify risk of PIRADS 3 lesions. Our results, however, also encourage the continued use of systematic biopsies in addition to the targeted biopsies.

55 MRI in Active Surveillance

56 Definitive Therapy vs. Active Surveillance over-detection over-treatment harm to patients under-sampling risk of progression

57 Typical patient scenario 66 year old healthy male PSA 5.5 prostate biopsy shows single core (out of 10 cores) Gleason 3+3 CaP, 1 mm length How best to monitor?

58 MRI in Active Surveillance surveillance tools limited to PSA, DRE and biopsy biopsy most important, but risk of under-sampling and risk of infection/bleeding MRI is promising to ensure better sampling of prostate (current) to reduce number of biopsies needed (future)

59 On confirmatory biopsy, Gleason score was upgraded in 79 of 388 (20%)patients Nov;188(5):1732-8

60 At 3 and 12 months of follow-up, 14% and 10% of the patients were risk-restratified on the basis of MP-MRI and MRGB. An overall PI-RADS score of 1 or 2 had a negative predictive value 100% (45/45) for detection of a GG 4 or 5 containing cancer upon MRGB Mar;49(3):165-72

61 Vancouver Experience 2006 to 2013 Vancouver General Hospital 603 patients with low risk CaP on AS 111 underwent multiparametric MRI primary outcome: termination of AS secondary outcome: detection of significant CaP detection of any Gleason 4 or 5 on follow-up biopsy

62 Vancouver Experience Feature # # patients 111 Age (yrs) 63 (58-68)* PSA (ng/ml) 6.1 (4.4-8)* Stage T1c 79 (71%) Gleason (13%) Lesion on MRI 68 (61%) * interquartile range

63 Vancouver Experience MRI detected 118 lesions with PIRADS 3 in 68 (61%) patients median lesion size 12.0 mm (IQR ±7.5) PIRADS 3 71 (60.2%) PIRADS 4 37 (31.4%) PIRADS 5 10 (8.4%) targeted biopsy in all 68 patients with MRI lesions (29 cognitive and 39 fusion)

64 Vancouver Experience Reason N (%) AS Termination - overall 27 (24%) Based on MRI results 17 (15%) Lesion size increase 2 (1.8%) Pathology progression on targeted biopsy 15 (14%) Independent of MRI results 10 (9%) PSA increase 1 (0.9%) Patient choice 3 (2.7%) Pathology progression on systematic biopsy 6 (5.4%)

65 Risk factor OR 95% C.I. P value PSA density ( 0.15 vs. > 0.15 ) Number of lesions (1-2 vs. > 2) PIRADS (3 vs. 4/5) ADC value ( vs. < 890) lesion size ( vs. > 10 mm)

66 Correlation between multi-parametric MRI findings and detection of prostate cancer in MR-guided Biopsy

67 Any CaP and significant scap were found in: -18% and 7% of PIRADS-3 lesions, -45% and 35% of PIRADS-4 lesions -71% and 64% of PIRADS-5 lesions

68 Back to our patient.. 66 year old healthy male PSA 5.5 prostate biopsy shows single core (out of 10 cores) Gleason 3+3 CaP, 1 mm length MRI 4-6 months after biopsy shows 8 mm PIRADS 3 lesion systematic biopsy + fusion biopsy single core Gl 3+3 1mm

69 MRI before first biopsy

70 Prostate Cancer Screening Digital rectal exam (DRE) Prostate specific antigen (PSA)

71 MRI for primary detection attractive concept, but need certainty that a negative MRI means there is no significant cancer important new idea: it is ok (and good!) to miss low risk cancer Villers et al. if MRI does not show a lesion, there is a 95% chance that the patient does not have a significant cancer (>0.5 ml, Gleason 7) this needs validation in other centres trials ongoing to determine safety

72 223 biopsy naïve men with elevated PSA any patient with PIRADS 3-5 lesion on MRI had MRIguided biopsy in addition to regular TRUS biopsy Any CaP Low risk CaP TRUS (n=223) 126 (56.5%) 47 (37.3%) MRI (n=142) 99 (69.7%) 6 (6.1%) Online Mar 14, 2014

73 MRI for primary detection MRI-guided biopsy reduced reduced the need for biopsy by 51%, decreased the diagnosis of low-risk PCa by 89% Ability of biopsy to rule out significant CaP: TRUS-guided 72% MRI-guided 97%

74 Take Home Messages the role of MRI in routine clinical practice is rapidly evolving different centres doing it differently variable access to technology across the province what we are doing now may be different in one year MRI enhances the detection of clinically significant prostate cancer in men with elevated PSA and in men on active surveillance in the future, we may replace biopsies with MRI even without prior biopsy but not yet!

75 Special Thanks to : Dr Goldenberg Dr Gleave Dr Black

76 Thank You!