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Advances in MR Imaging of PROSTATE CANCER

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. PROSTATE CANCER. Most common malignancy of men in US after skin cancer

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Advances in MR Imaging of PROSTATE CANCER

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  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 > 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 • It’s 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 PSAincreases PSA specificity • Low in CA • Elevated in benign prostatic hypertrophy (BPH) • If < 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 20–30% 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  1=Low …….. 5=High

  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 (3+4 vs 4+3)

  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 > 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 <5% of tissue resected T1b: Tumor incidental histologic finding in >5% of tissue resected T1c: Tumor identified by needle biopsy (eg, because of elevated PSA) T2: Tumor confined within prostate T2a: Tumor involves < 50% of 1 lobe T2b: Tumor involves > 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 vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

  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) < 2 cm • N2: One or more regional lymph nodes, largest > 2 cm but < 5 cm • N3: One or more regional lymph nodes, largest > 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) • M1c: Other site(s) with or without bone disease

  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. 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

  33. EXTRACAPSULAR EXTENSION - ECE

  34. 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

  35. SEMINAL VESICLE INVASION

  36. 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

  37. BLADDER & RECTAL INVASION

  38. 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 %

  39. 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)

  40. DYNAMIC CONTRAST ENHANCED MRI – DCE MRI

  41. WHY TUMORS ENHANCE DIFFERENTLY THAN NORMAL TISSUES • Cancers results in tumor angiogenesis • Increased no. of vessels • Increased permeability of vessels • Increased interstitial tissue space

  42. 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

  43. 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

  44. DCE MRI – Analysis of data • 3 methods of analysis • Qualitative  Easier Look at curves • Semi-Qualitative  Average Parameters from curves • Quantitative  Complicated Mathematical Modelling

  45. MR SPECTROSCOPY - MRS

  46. 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.

  47. 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

  48. TUMOR VOLUME

  49. 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

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

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