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Advances in MR Imaging of PROSTATE CANCER

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Advances in MR Imaging of PROSTATE CANCER Demetri Papadatos, MD, FRCPC Abdominal Imaging Radiologist Director, Abdominal Imaging Fellowship Director, Percutaneous ... – PowerPoint PPT presentation

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Title: Advances in MR Imaging of PROSTATE CANCER


1
Advances in MR Imaging of PROSTATE CANCER
  • Demetri Papadatos, MD, FRCPC
  • Abdominal Imaging Radiologist
  • Director, Abdominal Imaging Fellowship
  • Director, Percutaneous Radiofrequency Ablation
  • The Ottawa Hospital

2
PROSTATE CANCER
  • Most common malignancy of men in US
  • after skin cancer
  • At autopsy, prostate cancer is found in
  • 30 of men at age 50
  • almost 90 at age 90
  • About one in six men will be diagnosed with
  • prostate cancer during lifetime
  • However, only 1 / 34 will die of the disease

3
PROSTATE CANCER
  • Many cancers are indolent,
  • show no signs of clinical growth
  • Despite the long latent period,
  • second commonest cause of cancer death in
    American men over age 55

4
ETIOLOGY - RISK FACTORS
  • All men are at a risk of developing prostate
    cancer.
  • Age Greatest risk factor
  • risk increasing significantly after
    50 yrs
  • Family history Men with affected father or
    brother at increased risk
  • ACA Recommendation
    to start screening 10 yrs earlier
  • compare to general
    population
  • Genetic Factors abnormal genes in 10
  • but genetic
    testing is not available yet
  • Race
  • more frequent and aggressive in African American
    men
  • Environmental and dietary factors

5
HISTOPATHOLOGICAL TYPES
  • More than 95 of prostatic malignancies are
    adenocarcinomas
  • Rarely, a squamous or transitional cell neoplasm
  • Very rarely sarcoma

6
SCREENING
  • Routine Screening is offered
  • Men gt 50 yrs
  • With a life expectancy of at least 10 yrs
  • Screening consists of
  • Digital rectal examination
  • Serum PSA levels

7
PSA (Prostatic Specific Antigen)
  • Secreted into blood stream by the prostate gland
  • Its routine use for screening has lead an
    exponential rise in prostate cancers, which are
    being detected much earlier
  • Elevated PSA non specific
  • Also seen in benign prostatic hypertrophy (BPH)
  • and prostatitis (benign conditions)

8
If PSA elevated
  • Repeat PSA level a few weeks later
  • when probable occult prostatitis has resolved
  • Calculate PSA Density (PSA/gland volume)
  • increases PSA specificity
  • transrectal ultrasound (TRUS) gland volume
  • ? Nodules
  • Free PSA increases PSA specificity
  • Low in CA
  • Elevated in benign prostatic hypertrophy (BPH)
  • If lt 25 of PSA is free worrisome for cancer

9
DIAGNOSIS
  • Diagnosis of prostate carcinoma is usually made
  • by TRUS-guided core biopsy.
  • However, can have ve/rising PSA but ve biopsies
  • Dilemma
  • Do these patients have prostate cancer ???
  • If so, why are the biopsies negative ???

10
Transrectal Ultrasound (TRUS)and Biopsy (Bx)
  • TRUS can assess gland volume (PSAD)
  • and detect nodules
  • However, nodules may or may not represent cancer
  • Therefore, perform multiple biopsies in attempt
    to find the suspected cancer
  • TRUS is used to guide needle placement for
    biopsies

11
TRUS Bx
  • Systematic approach needed during biopsy session
  • in order to maximize the yield
  • Number and location of biopsies varies
  • Trend is to increase the number of biopsies
    obtained
  • Some cancers are located in nodules seen on TRUS
  • However, more aggressive cancer may be located
    elsewhere and not visible on TRUS
  • Malignant prostatic nodules tend to look
    hypoechoic (dark)
  • and demostrate increased vascularity

12
EXTENDED BIOPSY PROTOCOLS
  • Traditionally, a six biopsy protocol was used
  • Insufficient, tumours being missed and
    undergraded
  • In particular, midline and apicolateral PZ
    tumours were missed
  • 8 -10 biopsies improve diagnostic yield by 2030
    over traditional number of biopsies
  • Some centers recommend 24 biopsies (12 per side)
  • to get ve diagnosis
  • to accurately grade the tumor

13
PATHOLOGYGleason GRADE and Gleason Score
  • Gleason Grade ? 1Low .. 5High

14
GLEASON SCORE
  • A grade is assigned to the 2 largest foci of
    cancer
  • These 2 grades are added together to yield the
  • Gleason score (eg. Grade 3 Grade 4 Score of
    7)
  • Gleason Score varies between 2 and 10
  • The higher the Gleason score more aggressive
    tumor
  • NB Score of 7 (34 vs 43)

15
GLEASON SCORE
2-6 Low Risk 7 Intermediate risk 8-10
High risk
16
My prostate biopsy was positive, now what ?
  • Surgery only proven curative treatment
  • Only tumor confined to prostate is curable
  • Surgery HIGH morbidity/complications urinary
    incontinence sexual impotence
  • Need reliable staging tool to predict who will
    benefit from surgery
  • Before the advent of accurate staging with
    imaging, nomograms were developed

17
CLINICAL NOMOGRAMS
  • Originally designed to help predict the STAGE
  • (as determined after surgery) and best
    course of treatment.
  • "Partin tables"
  • originally developed by 2 urologists
  • (Alan W. Partin and Patrick C. Walsh)
  • based on accumulated data from hundreds of
    patients
  • treated for prostate cancer
  • Most recent version of the Partin Tables,
    released in 2001
  • based on data from 5000 patients
  • underwent radical prostatectomy at Johns Hopkins
  • Can be used to determine pre test probabability
    of unresectable disease and decide if surgery is
    worth the potential complications

18
ROLE OF MRI
  • MR can detect cancer but is not recommended as an
    initial screening tool (PSA, DRE, TRUS Bx)
  • However ? ? ve PSA but ve biopsy
  • Does this patient have cancer ???
  • MR helps target repeat biopsy to suspicious areas
  • Local Staging (to determine best treatment)

19
WHO NEEDS MRI STAGING
  • Most patients with prostate CA have indolent
    cancer
  • Will unlikely need any form of treatment
  • during their lives as cancer will never
  • manifest clinically
  • High (/- intermediate) risk groups
  • ( ie significant chance of tumor progression)

20
WHO NEEDS MRI STAGING
  • Staging MR would be cost effective if performed
  • ONLY in the subgroup of patients with
  • Palpable tumor
  • PSA gt 10
  • At least 50 positive cores for malignancy
  • High Gleason grade and score

21
IMAGING THE PROSTATE GLAND
  • Currently imaging at 1.5 Tesla scanner is
    recommended
  • Endorectal /Surface Coil MRI combination is best
    for anatomic detail
  • High SNR
  • High spatial resolution of 0.5 mm
  • 5 MR techniques will be discussed today
  • T2 Weighted Imaging
  • Dynamic contrast enhanced MRI (DCE-MRI)
  • MR Spectroscopic Imaging (MRSI)
  • Diffusion weighted Imaging (DWI)
  • Lymphotropic Nanoparticle-enhanced MRI
    (Ferumoxtran-10)

22
NORMAL ANATOMY
23
ANATOMY OF THE GLAND
  • Glandular (acinar) and nonglandular elements
  • I - Glandular prostate
  • 1- Outer components
  • Central zone (CZ)
  • Peripheral zones (PZ)
  • 2- Inner components
  • Periuretheral glands
  • Transitinal zone (TZ) (BPH)
  • II - Nonglandular portions
  • Prostatic urethra
  • Anterior fibromuscular band

24
ABNORMAL GLAND
25
DISTRIBUTION OF PROSTATE CANCER
  • Tumor location
  • 70 in Peripheral Zone, PZ
  • 20 in Transition Zone, TZ
  • 10 in Central Zone, CZ
  • Central gland most difficult to localize cancer
  • because of overlapping signal intensity
  • with normal gland / hypertrophy

26
LOCAL STAGING - IMPORTANCE
  • Accurate tumor staging is essential to determine
    appropriate treatment (ie is curative surgery an
    option ?)
  • Extracapsular Extension (ECE)
  • Seminal Vesicle Invasion (SVI)
  • Bladder/Rectal Invasion
  • Lymph Node Metastases
  • Only carcinomas confined within the prostate
    gland, are potentially curable by radical
    prostatectomy
  • Staging usually classified using TNM
    classification

27
TNM CLASSIFICATION
  • Primary tumor (T)
  • TX Primary tumor cannot be assessed
  • T0 No evidence of primary tumor
  • T1 Clinically inapparent tumor not palpable nor
    visible by imaging
  • T1a Tumor incidental histologic finding in lt5
    of tissue resected
  • T1b Tumor incidental histologic finding in gt5
    of tissue resected
  • T1c Tumor identified by needle biopsy (eg,
    because of elevated PSA)
  • T2 Tumor confined within prostate
  • T2a Tumor involves lt 50 of 1 lobe
  • T2b Tumor involves gt 50 of 1 lobe
  • T2c Tumor involves both lobes
  • T3 Tumor extends through the prostate capsule
  • T3a Extracapsular extension (unilateral or
    bilateral) ECE
  • T3b Tumor invades seminal vesicle(s) SVI
  • T4 Tumor is fixed or invades adjacent structures
    other than seminal

28
TNM CLASSIFICATION
  • Regional lymph nodes (N)
  • Regional lymph nodes are the nodes of the true
    pelvis
  • Distant lymph nodes are outside the true pelvis
  • NX Regional lymph nodes were not assessed
  • N0 No regional lymph node metastasis
  • N1 Single regional lymph node (inside the
    pelvis) lt 2 cm
  • N2 One or more regional lymph nodes, largest gt 2
    cm but lt 5 cm
  • N3 One or more regional lymph nodes, largest gt 5
    cm
  • Distant metastasis (M)
  • MX Distant metastasis cannot be assessed (not
    evaluated by any modality)
  • M0 No distant metastasis
  • M1 Distant metastasis
  • M1a Non-Regional lymph node(s)
  • M1b Bone(s)

29
STAGING OBJECTIVES
  • To confirm organ-confined disease
  • radical surgical prostatectomy could be offered
  • without adjuvant radiation therapy.
  • If disease is largely organ-confined with small
    volume periprostatic or seminal vesicle spread,
    radical radiotherapy can still be offered
  • with / without pelvic nodal irradiation or
  • with / without adjuvant hormonal therapy
  • To confirm clinically suspected apical tumor or
    extent of LN metastases which will affect
    radiotherapy margins.

30
TIMING FOR MRI
  • MRI should be delayed at least 4-8 weeks after
    biopsy
  • Post biopsy hemorrhage may hamper tumor
    detection in
  • the gland
  • May result in under or overestimation of tumor
    presence
  • and local extent
  • MR exclusion sign cancers are resistant to the
  • development of post biopsy hemorrhage

31
LOCAL STAGINGT STAGING
32
LOCAL STAGING
  • Tumor extent
  • Extra capsular extension
  • Seminal vesicle invasion
  • Volume of tumor
  • Aggressiveness

33
ORGAN CONFINED DISEASE
  • Primary tumor TNM Stage of T2 or less
  • Suitable for radical surgery
  • Nerve sparing radical surgery if neurovascular
    bundles are clear
  • Clinical estimation of the organ confined disease
    is
  • based on clinical nomograms which takes into
    account
  • PSA
  • DRE
  • Gleason score
  • MR imaging has been shown to have an incremental
    value additive to clinical nomograms

34
MRI SIGNS OF UNRESECTABLE DISEASE ( TNM Stage gt
T2 )
  • Extra capsular extension - ECE
  • Invasion of periprostatic fat
  • Invasion of neuromuscular bundle
  • Seminal Vesicle Invasion - (SVI)
  • Invasion of adjacent organs (Bladder, Rectum)
  • Metastases to pelvic lymph nodes

35
EXTRACAPSULAR EXTENSION - ECE
36
ECE
  • Most imp to diagnose
  • Endorectal coil imaging with T1 T2W seq. only
  • OR
  • Endorectal imaging with spectroscopy

37
MRI SIGNS OF ECE
  • Assessed on AXIAL CORONAL images
  • Contour deformity with step off or angulated
    margin
  • Irregular bulge or capsule retraction
  • Capsular breach direct tumor extension
  • Obliteration of rectoprostatic angle
  • Asymmetry of neurovascular bundles

38
SEMINAL VESICLE INVASION
39
MRI SIGNS OF SEMINAL VESICLE INVASION (SVI)
  • Combined AXIAL, SAGITAL CORONAL images
  • facilitates detection of SV invasion
  • Contiguous low SI from base of gland in SV
  • Extension of soft tissue along ejaculatory ducts
  • Asymmetric decrease in SI of SV
  • Decreased conspicuity of SV wall on T2WI

40
BLADDER RECTAL INVASION
41
T2WI SENITIVITY AND SPECIFICITY
  • Varies widely for cancer detection
  • Without endorectal coil
  • Sensitivity 45
  • Specificity 73
  • With Endorectal coil
  • Sensitivity 77 - 91
  • Specificity 27 - 61

42
How do we increase specificity ?
  • Keep Endorectal Coil MRI T2 imaging
  • (high sensitivity) and add
  • Contrast-enhanced MRI (CE-MRI)
  • MR Spectroscopic Imaging (MRSI)
  • Diffusion-weighted MRI (DWI)

43
DYNAMIC CONTRAST ENHANCED MRI DCE MRI
44
WHY TUMORS ENHANCE DIFFERENTLY THAN NORMAL TISSUES
  • Cancers results in tumor angiogenesis
  • Increased no. of vessels
  • Increased permeability of vessels
  • Increased interstitial tissue space

45
DCE MRI
  • Fast GRE seq. can scan entire vol. of gland in
    few seconds
  • Various perfusion parameters are electronically
    extracted according to time seq.
  • Relative peak enhancement is most reliable
    perfusion parameter for cancer detection
  • Improves specificity compared to T2W scans
  • Tumors can be detected with higher accuracy but
    it does not improve staging

46
DCE MRI - IMPROVEMENT IN DETECTION RATES
  • Peripheral zone cancers
  • Sensitivity 96
  • Specificity 97
  • Compared to 75 and 53 respectively on T2WI
  • Not tested in multi institutional trials
  • Suffers from lack of uniformly accepted analytic
    method
  • Still of unproven benefit as per ACR guidelines

47
DCE MRI Analysis of data
  • 3 methods of analysis
  • Qualitative ? Easier
  • Look at curves
  • Semi-Qualitative ? Average
  • Parameters from curves
  • Quantitative ? Complicated
  • Mathematical Modelling

48
MR SPECTROSCOPY - MRS
49
SPECTROSCOPY NORMAL SPECTRAL ANALYSIS
  • 3D proton MR spectroscopic metabolic mapping of
    the entire gland is possible with a resolution of
    0.24 ml per voxel.
  • Proton MR spectroscopy displays concentrations of
    citrate, creatine, and choline metabolites found
    in the prostate gland and cancer.
  • Normal prostate tissue contains high levels of
    citrate -higher in the PZ than in the central
    gland.

50
SPECTROSCOPY SPECTRAL ANALYSIS
  • Healthy peripheral-zone voxels typically have
  • diagnostic levels of Cit with (Cho Cr)/Cit
    ratios
  • less than 0.5
  • Because of the proximity of the choline and
  • creatine peaks at 1.5-T MR unit two peaks
    cannot be separated

51
TUMOR VOLUME
52
TUMOR VOLUME
  • There is an association between primary tumor
    volume and local extent of disease, progression,
    and survival
  • A review of a large number of prostate cancers in
    surgical and autopsy specimens showed
  • Capsular penetration
  • Seminal vesicle invasion and
  • Lymph node metastases
  • usually found only with tumors larger than 1.4 cc

53
TUMOR VOLUME
  • Another study - ECE in 18 with vol. lt 3 cc
  • 79 with volume gt 3 cc
  • Tumor volume significant predictor of ECE
  • Bx, TRUS and T2-MRI disappointing in volume
    estimation
  • MRS provides more accurate volume estimation

54
ROLE OF SPECTROSCOPY IN ESTIMATING TUMOR VOLUME
  • Relative tumor volume is determined on MRS
  • ( counting the voxels containing abnormal
    spectra )
  • Improves Dx of ECE for both experienced and less
    experienced reader
  • Decrease inter observer variability further
    studies required to assure improvement in the
    performance of truly inexperienced reader

55
MR SPECTROSCOPY - MRS
  • Technically demanding and time consuming
  • Improvement in diagnostic accuracy and staging
    have been reported but not proved in multi
    institutional trials
  • ACR clinical trial is currently underway
  • Currently cannot be considered as routine
    diagnostic tool

56
Diffusion-weighted Imaging (DWI)
  • Diffusion is the process of thermally induced
    random molecular displacement Brownian motion
  • Diffusion properties of tissues are related
  • Amount of tissue water
  • Tissue permeability
  • Cancer tends to have restricted diffusion due to
  • High cell densities
  • Abundant intracellular membranes

57
DWI
  • ADVANTAGES
  • Short acquisition time
  • High contrast resolution between tumor and normal
    tissue
  • No need for endorectal Coil
  • DISADVANTAGES
  • Poor spatial resolution
  • Potential risk of image distortion by post biopsy
    Hg

58
LOCAL STAGING N STAGING
59
ABNORMAL NODES
  • Early metastases can occur in small nodes
  • Size and shape of nodes inaccurate for staging
  • ABNORMAL NODES
  • Rounded configuration
  • Short axis gt 10 mm if oval, gt 8 mm if round
  • T1 OR T2 SI not helpful
  • Enhancement suggestive of metastatic lymph node

60
SHORTCOMINGS- NODAL STAGING
  • Normal sized nodes - contain cancer as micro
    metastases
  • Enlarged nodes may be reactive

61
DETECTION OF ABNORMAL LYMPH NODES
  • Neither CT nor MRI is accurate as laparoscopic
    nodal dissection
  • Initial step prior to radical prostatectomy
    remains nodal dissection
  • MR is at least as accurate as CT in nodal staging
  • If good chance the prostate cancer has already
    spread
  • to the lymph nodes laparoscopic lymph node
    dissection
  • is a minimally invasive procedure to begin
    with

62
Lymphotropic Nanoparticles
  • ULTRASMALL SUPER PARAMAGNETIC MR contrast agents
    taken up by macrophages
  • Distributes to LNs throughout the body
  • Injected intravenously and imaged 24 hrs later
  • susceptibility effect on T2 MR images
  • Cannot enter tumor (no macrophages)
  • Can differentiate normal/reactive lymph nodes
    from malignant ones
  • Iron based contrast agents not approved by FDA
  • (Ferumoxtran-10)

63
Future trends
  • 3T MRI
  • Increased SNR
  • Increased spatial resolution
  • ? Assessment of microscopic disease
  • ? Need for Endorectoil Coil
  • Standardized technique for CE-MRI with
    availability of vendor software
  • Approval of Lymphotropic Nanoparticles for
    accurate nodal staging

64
Thanks to
  • Arifa Sadaf
  • Radiology, Radiographics and AJR
  • Researchers who develop Prostate MR

65
Thank You
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