David Sher
Gillian Lieberman, MD
March 2002
Prostate Cancer:
Imaging in Diagnosis and Treatment
David Sher, Harvard Medical School III
Gillian Lieberman, MD
David Sher
Gillian Lieberman, MD
Introduction
• The prostate gland is a walnut-sized exocrine gland
that surrounds the urethra between the bladder neck
and the genitourinary membrane
• Its secretions primarily function in semen gelation,
coagulation and liquefaction
– Prostatic proteins are also involved in coating/uncoating the
spermatozoa and in interactions with cervical mucus
• Disease processes range from benign (benign
prostatic hyperplasia, BPH) to inflammatory
(prostatitis) to malignant (prostate cancer)
2
David Sher
Gillian Lieberman, MD
Anatomic Relationships
Axial
Sagittal
Gray’s Anatomy Online. http://www.bartleby.com/107/
Coakley FV, Hricak H. Radiologic Anatomy of the Prostate. Radiologic Clinics NA; 38(1): 15-30.
Coronal
3
David Sher
Gillian Lieberman, MD
Prostate Anatomy
Lobar Anatomy
Zonal Anatomy
Coakley FV, Hricak H. Radiologic Anatomy of the Prostate. Radiologic Clinics NA; 38(1): 15-30.
4
David Sher
Gillian Lieberman, MD
Prostate Cancer: Presentation
Prostate Cancer
Detected Early
Elevated PSA
Abnormal DRE
False Positive
Prostate Cancer
Detected Late
Acute
Prostate Cancer
Chronic
BPH
Extra-Prostatic Growth
Biopsy
BPH
TURP
Chronic Prostatitis
Outflow Obstruction
Metastatic Disease
Prostate Cancer
Intrinsic Organ Pathology
BPH
Other Metastatic Disease
Bladder Disease
Urethral/Penile Disease
Malignant Extension
Acute Urinary Retention
Acute Prostatitis
Ejaculation
5
David Sher
Gillian Lieberman, MD
Prostate Cancer: Basics
•
Prostate cancer is the most commonly diagnosed cancer in men
(~ 200,000 cases/year)
– Lifetime risk of developing prostate cancer: 16%
– Risk of dying from prostate cancer: 3.4%
•
•
•
•
•
It is the 2nd leading cause of cancer-related mortality among
men (~40,000 deaths/year)
In general, the malignancy is slow-growing, although the
prognosis varies drastically according to stage
PSA screening has undoubtedly detected more cancers, with a
debatable survival benefit
Risk factors include older age, black race (RR 1.5), family
history (1st degree relative doubles risk)
Radiology plays a vital role in diagnosis and treatment
6
David Sher
Gillian Lieberman, MD
Diagnosis
• Diagnosis is made by
transrectal ultrasound
(TRUS) guided prostate
needle biopsy
• Classically the biopsies
are performed using a
sextant approach
http://www.marinurology.com/articles/cap/learning/trusp.htm
Littrup PJ, Bailey SE. Prostate Cancer: The Role of TRUS & Its Impact on
Cancer Detection & Mgmt. Radiologic Clinics NA; 38(1): 87-113.
7
David Sher
Gillian Lieberman, MD
TNM Staging
•
•
T0 No evidence of primary tumor
T1 Clinically unapparent, not palpable or visible by
imaging
–
–
–
•
T2
–
–
–
•
T3
–
–
–
•
T1a Incidental histological finding in  5% of resected tissue
T1b Incidental histological finding in > 5% of resected tissue
T1c Identified by needle biopsy but not palpable or visible by imaging
Confined to prostate
T2a Involves half a lobe or less
T2b Involves more than half a lobe but not both lobes
T2c Involves both lobes
Extends through the prostatic capsule
T3a Extends unilaterally
T3b Extends bilaterally
T3c Invades seminal vesicles
T4 Fixed or invades adjacent structures other than
seminal vesicles
–
–
T4a Invades bladder neck, external sphincter, or rectum
T4b Invades levator muscles or is fixed to pelvic wall
Catalona WJ. Management of Cancer of the Prostate. NEJM; 1994. 331(15): 996-1004.
8
David Sher
Gillian Lieberman, MD
Prognosis
• Patients can be risk-stratified into 3 groups based
upon 1992 AJCC stage, PSA, and Gleason score
• Low risk: >85% 5-year PSA failure-free survival
– Stage T1c,2a AND PSA  10 ng/ml AND Gleason score  6
• Intermediate: 50% 5-year PSA failure-free survival
– Stage T2b OR 10 < PSA  20 ng/ml OR Gleason score 7
• High risk: ~33% 5-year PSA failure-free survival
– Stage T2c OR PSA > 20 ng/ml OR Gleason score  8
D’Amico A. Combined-modality staging for localized adenocarcinoma of the prostate. Oncology; 15(8):1049-59.
9
David Sher
Gillian Lieberman, MD
Workup for Prostate CA
• Following an abnormal PSA or DRE, the first step is
transrectal ultrasound-guided biopsy
• Depending on risk-stratification, endorectal MRI is
performed to evaluate extra-capsular spread
• A metastatic workup is required for patients at highrisk for metastasis: Gleason score > 7; PSA > 20; or
clinical stage T3 or T4
• The result of these studies is critical to determining a
treatment plan (i.e curative approach vs. palliative)
10
David Sher
Gillian Lieberman, MD
Transrectal Ultrasound (TRUS)
•
•
•
Transrectal ultrasound is the imaging modality that has
revolutionized prostate cancer diagnosis.
TRUS utilizes a transrectal probe that operates at 5-7 MHz
TRUS allows the radiologist or urologist to:
–
–
–
–
–
•
Estimate the size of the prostate
Determine “estimated PSA” (.12 x volume)
Identify suspicious lesions
Image vascular flow
Biopsy the prostate
Despite the rapidly improving technology, the sensitivity and
positive predictive value of TRUS-directed biopsy remain low
– A sextant biopsy technique has a sensitivity of 65%
Statistics from: Gore JL, Shariat SF, et al. Optimal combinations of systematic sextant and laterally directed
biopsies for the detection of prostate cancer. J of Urology; 165(5): 1554-1559.
11
David Sher
Gillian Lieberman, MD
TRUS: BPH, Patient 1
Hypertrophied central gland
Peripheral zone
Gland volume: 134 cc
R
L
Axial
Large central gland
Peripheral zone
Sagittal
Images courtesy Robert Kane, MD
12
David Sher
Gillian Lieberman, MD
TRUS: Prostate Cancer, Patient 2
TUR Defect
Hypoechoic nodule
Gland volume: 25 cc
R
L
Axial
Central gland
Hypoechoic nodule
Sagittal
Images courtesy Robert Kane, MD
13
David Sher
Gillian Lieberman, MD
TRUS: Prostate Cancer, Patient 3
Central gland
Peripheral zone
R
L
Hypoechoic nodule
Gland volume: 18 cc
Axial
R
L
Seminal vesicles
Axial
Images courtesy Robert Kane, MD
14
David Sher
Gillian Lieberman, MD
Improving TRUS: Doppler
85% of men with prostate
cancers > 5mm have visibly
increased flow on Doppler
In this healthy patient, the flow
is symmetric and radial
Axial
The addition of a contrast agent
(microbubbles) enhances the
signal-to-noise ratio
Axial
This prostate cancer is clearly
visible with contrast-enhanced
color Doppler
Frauscher F, Klauser A, Halperin EJ.Advances in Ultrasound for the Detection of Prostate Cancer.
Ultrasound Quarterly; 18(2): 135-142.
15
David Sher
Gillian Lieberman, MD
Prostate MRI
•
•
•
MRI of the prostate is the only imaging modality that can directly
visualize the normal prostate substructure and cancers that
arise therein
The optimal MRI technique uses a body
excitation coil (at least 1.5 T), and a pelvic
phased-array coil and endorectal coil
for reception
The goal of imaging is tumor detection and staging:
– Visualizing the capsule, neurovascular bundles, and seminal
vesicles
– Staging accuracy is now 75-90%
•
The use of ERMR also allows for sophisticated applications:
– MR spectroscopy
– MR-guided procedures (brachytherapy, biopsy)
Kurhanewicz J, Vigneron DB et al. The Prostate: MR Imaging and Spectroscopy.
Radiologic Clinics NA; 38(1): 115-138.
16
David Sher
Gillian Lieberman, MD
MR Prostate: BPH, Patient 4
Patient is a 61 yo man who
p/w a PSA increase from 2.6
in 1993 to 9.5 in 2002. All
biopsies were negative.
Bladder
Seminal vesicles
ER Coil in rectum
Axial
BIDMC PACS
Central gland
Peripheral zone
ER Coil in rectum
Axial
BIDMC PACS
17
David Sher
Gillian Lieberman, MD
MR Prostate: BPH, Patient 4
Seminal vesicles
Peripheral zone
Hypertrophied central gland (L>R)
Corpus cavernosum
Corpus spongiosum
Coronal
BIDMC PACS
Seminal vesicles
Bladder
Endorectal coil
Peripheral zone
Sagittal
Hypertrophied central gland (L>R)
BIDMC PACS
18
David Sher
Gillian Lieberman, MD
MR Prostate, Patient 5
Patient is a 61 yo man who p/w a PSA increase from 1.7 to 3.4. A palpable nodule was
felt on DRE, and subsequent TRUS-guided biopsy revealed Gleason 4+3. He
subsequently underwent a radical prostatectomy.
Central gland
Peripheral zone
Low-intensity signal in lateral left
lobe, extending to capsule
Rectoprostatic angle preserved
Obdurator
Endorectal coil
Puborectalis
Axial
BIDMC PACS
19
David Sher
Gillian Lieberman, MD
MR Prostate: Index Patient
The patient is a 69 yo man
with long-standing Crohn’s
whose PSA rose from 3.5
to 4.2 in 2002. A TRUS was
performed. An MR was
performed without ER coil.
Central gland
Calcifications
Hypoechoic nodule R
L
Axial
BIDMC PACS
Central gland
Peripheral zone
Hypointense region in right PZ
Axial
BIDMC PACS
20
David Sher
Gillian Lieberman, MD
MR Prostate, Patient 5
The patient is a 75 yo
man with recurrent
prostate cancer. He is
currently on hormonal
therapy.
He recetly presented to
the BID with acute renal
failure.
Bladder (Foley)
Extracapsular lowintensity mass
Rectal Coil
Axial
Bladder (Foley)
Rectal Coil
Extracapsular
low-intensity
mass
Sagittal
Coronal
Images BIDMC PACS
21
David Sher
Gillian Lieberman, MD
MR Spectroscopy
•
Prostatic secretions contain 24-1300x more citrate than blood
– Cancer cells are unable to produce this physiologic metabolite
– In addition, both the density and metabolism of cancer cells lead
to elevated concentrations of choline.
•
Proton MR spectroscopy can evaluate these changing
concentrations
•
•
This image overlays the spatial
signal intensity for citrate
(normal tissue) with that choline
(neoplasm)
As this technology matures, it
will provide a means of:
localizing cancer, assessing
ECE, measuring
aggressiveness, and gauging
treatment success
Kurhanewicz J, Vigneron DB et al. The Prostate: MR Imaging and Spectroscopy.
Radiologic Clinics NA; 38(1): 115-138.
22
David Sher
Gillian Lieberman, MD
Prostate Metastasis
•
•
Either advanced clinical stage or suspicion of recurrent disease (rising
PSA or new symptoms) prompt a search for metastasis
Work-up includes
– Plain films of chest and bone
• Cheap, can be used to detect bone or lung metastases
– Abdominal/pelvic CT (or MR) to evaluate visceral metastases
– Bone scintigraphy has a proven role in detecting bone
metastases
• In the initial work-up, it is most commonly used in intermediate to highrisk patients
• It is always used in rising PSA following treatment
– Radioimmunoscintigraphy
• Currently in use (not at BID), but its merits are still under investigation
23
David Sher
Gillian Lieberman, MD
Metastatic Workup: Plain Films
•
•
85% of patients dying from prostate cancer have bone
metastases
80% of bone metastases are osteoblastic
– They have a tendency to diffusely infiltrate bone
•
Plain radiographs are insensitive for picking up metastases,
since the bone density must increase by 50% to be visualized
AP film of pelvis showing
diffuse blastic metastases
BIDMC teaching collection
Yu KY, Hawkins RA. The prostate: Diagnostic Evaluation of Metastatic Disease.
Radiologic Clinics NA; 38(1): 139-157.
24
David Sher
Gillian Lieberman, MD
Metastatic Workup: Bone Scan
•
Radionuclide bone scintigraphy is the most sensitive technique to
detect bone metastases.
– In one study that performed bone scans in asymptomatic patients with a
PSA > 20 ng/ml, the sensitivity was 99%
– This sensitivity comes at the cost of low specificity, as Paget’s disease, DJD
and trauma can commonly produce false-positives
Technetium-99m
diphosphonate bone scan
showing prostate cancer
metastases to:
Pelvis, femurs, spine,
scapulae, humeri, and ribs
Yu KY, Hawkins RA. The prostate: Diagnostic Evaluation of Metastatic Disease. Radiologic Clinics
NA; 38(1): 139-157.
25
David Sher
Gillian Lieberman, MD
Metastatic Workup: CT
• The diagnostic use of CT is limited by its poor
resolution of prostatic anatomy and capsule.
• It plays two key role in prostate cancer:
– Staging advanced cancer
– Planning of external-beam radiotherapy
This is patient 5, whose MR
was recently presented. This
CT was part of his recurrent
prostate CA workup.
Symphisis pubis
Bladder (Invaded)
Prostate
BIDMC PACS
26
David Sher
Gillian Lieberman, MD
Metastatic Workup:
Radioimmunoscintigraphy
Radioimmunoscintigraphy consists of radiolabelled monoclonal
antibodies to prostate antigen, using SPECT for acquisition
– The most studied antibody (trade name Prostascint) is to prostate
specific membrane antigen (PSMA)
– Its use includes:
• Evaluation of high-risk patients for nodal and visceral metastasis
– Sensitivity 60%; Specificity 70%; PPV 60%; NPV 70%
• Assessing recurrent disease in prostatic fossa
– Sensitivity 49%; Specificity, 70%; PPV, 50%; NPV 70%
• Assessing potential response to salvage radiotherapy
– Preliminary reports suggest Prostascint stratifies responders
– Despite all of these data, its utility is hotly debated
• Overall there are few studies of Prostascint
– Of those studied, there are still strong detractors
• Low signal-to-noise ratio (up to 40% are uninterpretable) makes
interpretation difficult
Urology 2001. 57(3):399-401
Urology 2001. 57(3):402-406
27
David Sher
Gillian Lieberman, MD
Metastatic Workup: Prostascint
59 yo man with
newly diagnosed
prostate cancer
Mesenteric lymph nodes
(Positive biopsy)
Known prostate cancer
Supraclavicular lymph node
(Positive biopsy)
Suspicious punctate deposition
(Negative CT)
Anderson RS, Eifert B et al. Radioimmunoguided surgery using indium-111 capromab to diagnose
supraclavicular metastasis from prostate cancer. Urology 2000. 56(4): 669.
28
David Sher
Gillian Lieberman, MD
Treatment
• A treatment plan is dependent on the stage, overall
health of the patient, and patient preference
• Localized disease
– Watchful waiting
– Radical prostatectomy
– Radiation therapy
• External beam radiation therapy (EBRT)
• Brachytherapy
• Advanced disease
– Hormonal therapy
– Chemotherapy
29
David Sher
Gillian Lieberman, MD
External Beam Radiation Therapy
• External beam radiation therapy (EBRT) is an
attractive option because it avoids surgery and has a
lower rate of impotence and urinary incontinence
• Long-term outcome in prostate cancer is similar to
radical prostatectomy
• Prior to the advent of CT, radiation fields were
determined by contrast enhanced plain films
• Classically, the superior border of the field was the
L5-S1 interspace, and the inferior border was the
inferior border of the ischial tuberosities
30
David Sher
Gillian Lieberman, MD
3-D Conformal Beam Radiotherapy
•
Conformal beam radiotherapy attempts to “conform” the radiation beam
to the tumor in order to minimize exposure to healthy tissue
This patient is a 61 yo man with a PSA .6. Cancer (Gleason
3+3) was detected by abnormal DRE.
Step 1: Create 3-D model from CT
Images from BWH Radiation Oncology
31
David Sher
Gillian Lieberman, MD
EBRT Continued
Sagittal
Step 2: Beams are
created to treat planning
target volume
Images from BWH Radiation Oncology
Coronal
32
David Sher
Gillian Lieberman, MD
Brachytherapy
•
•
•
•
•
Prostate brachytherapy is the placement of radioactive seeds into the prostate
It is most effective in low-risk cancers, and the 5 year survival of this group is equal with RP
and EBRT
Typically, ~100 seeds containing I-125 or Pd-103 are permanently implanted into the
prostate
The seeds are usually implanted under real-time TRUS guidance
Dosimetry is performed 1-30 days after the procedure, usually by CT
–
Newer systems allow real-time dosimetry
Needle
Insertion
Real Time
Imaging
Radiologic
Evaluation
Reposition
Needle
Dosimetric
Evaluation
Place
seeds
Dose
Evaluation
Off-line
dosimetry
Plan
Modification
Reimplantation
33
Algorithm courtesy Rob Cormack, Ph.D.
David Sher
Gillian Lieberman, MD
TRUS-Guided Brachytherapy
3-D Dosimetry
Planning Grid
http://www.emedicine.com/med/topic3147.htm
http://www.cms-stl.com/image_gallery/brachytherapy/brachytherapy_ultrsound_brachy.htm
34
David Sher
Gillian Lieberman, MD
MR-Guided Brachytherapy
•
•
BWH has pioneered the use of MR-guided brachytherapy, which
takes advantage of its superior resolution
Seed placement and dosimetry are essentially monitored in real
time, optimizing dose distribution
The patient is a 65 yo man with T1c prostate cancer.
Images courtesy Rob Cormack, Ph.D.
35
David Sher
Gillian Lieberman, MD
MR Brachytherapy Continued
Planned isobars
3-D reconstruction
Central gland
Peripheral zone
Seeds
Needles
Images courtesy Rob Cormack, Ph.D.
3-d reconstruction from http://splweb.bwh.harvard.edu:8000/pages/comonth/99/july/fig4.jpg
36
David Sher
Gillian Lieberman, MD
Acknowledgements
•
•
•
•
•
•
•
•
•
•
Haldon Bryer, MD
Robert Cormack, PhD (JCRT, BWH)
Robert Kane, MD
Jonathan Kruskal, MD
Andrea Ng, MD, MPH (JCRT, BWH)
Tony Parker, MD, PhD
Buddy Weise, MD, PhD
Gillian Lieberman, MD
Pamela Lepkowski
Larry Barbaras and Cara Lyn D’amour
37
David Sher
Gillian Lieberman, MD
References: Literature
Anderson RS, Eifert B et al. Radioimmunoguided surgery using indium-111 capromab to
diagnose supraclavicular metastasis from prostate cancer. Urology; 56(4): 669.
Barry MJ. PSA Testing for Early Diagnosis of Cancer. NEJM; 344(18): 1373-1377.
Catalona WJ. Management of Cancer of the Prostate. NEJM; 331(15): 996-1004.
Coakley FV, Hricak H. Radiologic Anatomy of the Prostate. Radiologic Clinics NA; 38(1): 15-30.
D’Amico A. Combined-modality staging for localized adenocarcinoma of the prostate. Oncology;
15(8):1049-59.
Frauscher F, Klauser A, Halperin EJ.Advances in Ultrasound for the Detection of Prostate
Cancer. Ultrasound Quarterly; 18(2): 135-142.
Gore JL, Shariat SF, et al. Optimal combinations of systematic sextant and laterally directed
biopsies for the detection of prostate cancer. J of Urology; 165(5): 1554-1559.
Hayward SW, Cunha GR. The Prostate: Development and Physiology. Radiologic Clinics NA;
38(1): 1-14.
Kurhanewicz J, Vigneron DB et al. The Prostate: MR Imaging and Spectroscopy.Radiologic
Clinics NA; 38(1): 115-138.
Lange P. Prostascint scan staging prostate cancer. Urology; 57(3): 402-406.
Littrup PJ, Bailey SE. Prostate Cancer: The Role of TRUS & Its Impact on Cancer Detection &
Mgmt. Radiologic Clinics NA; 38(1): 87-113.
Presti JC. Prostate Cancer: Assessment of risk using DRE, tumor grade, PSA, and systematic
biopsy. Radiologic Clinics NA; 38(1): 49-58.
Sartor O, McLeod D. Indium-111-capromab pendetide scans: an important test relevant to
clinical decision making. Urology; 57(3):399-401.
Speight JL, Roach M. Imaging and radiotherapy of the prostate. Radiologic Clinics NA; 38(1):
159-177.
Yu KY, Hawkins RA. The prostate: Diagnostic Evaluation of Metastatic Disease. Radiologic
38
Clinics NA; 38(1): 139-157.
David Sher
Gillian Lieberman, MD
References: WWW
•
Gray’s Anatomy Online: http://www.bartleby.com/107/
•
Overview of treatment for early prostate cancer:
http://www.utdol.com/application/topic.asp?file=prost_ca/4541
•
Overview of the clinical presentation, diagnosis and staging of prostate
cancer:http://www.utdol.com/application/topic.asp?file=prost_ca/2
848
•
Prostate cancerr: Brachytherapy:
http://www.emedicine.com/med/topic3147.htm
Radiation therapy for early prostate cancer:
http://www.utdol.com/application/topic.asp?file=prost_ca/6680
TRUS: http://www.marinurology.com/articles/cap/learning/trusp.htm
Ultrasound-guided template and dose: http://www.cms
stl.com/image_gallery/brachytherapy/brachytherapy_ultrsound_br
achy.htm
•
•
•
39