BURDEN OF PROSTATE CANCER: ADDRESSING ISSUES OF DIAGNOSIS ...
Prostate Cancer: Imaging in Diagnosis and Treatment
Transcript of Prostate Cancer: Imaging in Diagnosis and Treatment
David SherGillian Lieberman, MD
Prostate Cancer: Imaging in Diagnosis and Treatment
David Sher, Harvard Medical School IIIGillian Lieberman, MD
March 2002
David SherGillian Lieberman, MD
2
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)
David SherGillian Lieberman, MD
3
Anatomic Relationships
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.
Axial
Sagittal Coronal
David SherGillian Lieberman, MD
4
Prostate AnatomyLobar Anatomy Zonal Anatomy
Coakley FV, Hricak H. Radiologic Anatomy of the Prostate. Radiologic Clinics NA; 38(1): 15-30.
David SherGillian Lieberman, MD
5
Prostate Cancer: Presentation
Prostate Cancer
Biopsy
TURP
Acute Urinary Retention
Acute Prostatitis
Ejaculation
Acute
BPH
Chronic Prostatitis
Chronic
False Positive
Elevated PSA
Prostate Cancer
BPH
Extra-Prostatic Growth
Abnormal DRE
Detected Early
Prostate Cancer
BPH
Bladder Disease
Urethral/Penile Disease
Malignant Extension
Outflow Obstruction
Intrinsic Organ Pathology
Other Metastatic Disease
Metastatic Disease
Detected Late
Prostate Cancer
David SherGillian Lieberman, MD
6
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
David SherGillian Lieberman, MD
7
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.htmLittrup PJ, Bailey SE. Prostate Cancer: The Role of TRUS & Its Impact on
Cancer Detection & Mgmt. Radiologic Clinics NA; 38(1): 87-113.
David SherGillian Lieberman, MD
8
TNM Staging• T0 No evidence of primary tumor• T1 Clinically unapparent, not palpable or visible by
imaging– 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
• T2 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
• T3 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.
David SherGillian Lieberman, MD
9
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.
David SherGillian Lieberman, MD
10
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 high- risk 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)
David SherGillian Lieberman, MD
11
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.
David SherGillian Lieberman, MD
12
TRUS: BPH, Patient 1Hypertrophied central gland
Peripheral zoneGland volume: 134 cc
Large central gland
Peripheral zone
Images courtesy Robert Kane, MD
Axial
Sagittal
R L
David SherGillian Lieberman, MD
13
TRUS: Prostate Cancer, Patient 2TUR Defect
Hypoechoic noduleGland volume: 25 cc
Central gland
Hypoechoic nodule
Images courtesy Robert Kane, MD
Axial
Sagittal
R L
David SherGillian Lieberman, MD
14
TRUS: Prostate Cancer, Patient 3Central gland
Peripheral zone
Hypoechoic noduleGland volume: 18 cc
Seminal vesicles
Images courtesy Robert Kane, MD
Axial
Axial
R L
R L
David SherGillian Lieberman, MD
15
Improving TRUS: Doppler85% of men with prostate cancers > 5mm have visibly increased flow on Doppler
In this healthy patient, the flow is symmetric and radial
The addition of a contrast agent (microbubbles) enhances the signal-to-noise ratio
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.
Axial
Axial
David SherGillian Lieberman, MD
16
• 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)
Prostate MRI
Kurhanewicz J, Vigneron DB et al. The Prostate: MR Imaging and Spectroscopy.Radiologic Clinics NA; 38(1): 115-138.
David SherGillian Lieberman, MD
17
MR Prostate: BPH, Patient 4Patient 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
Central gland
Peripheral zone
ER Coil in rectum
Axial
AxialBIDMC PACS
BIDMC PACS
David SherGillian Lieberman, MD
18
MR Prostate: BPH, Patient 4
Coronal
Sagittal
Seminal vesicles
Peripheral zone
Hypertrophied central gland (L>R)
Corpus cavernosum
Corpus spongiosum
Seminal vesicles
Bladder
Endorectal coil
Peripheral zone
Hypertrophied central gland (L>R)BIDMC PACS
BIDMC PACS
David SherGillian Lieberman, MD
19
MR Prostate, Patient 5Patient 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
AxialBIDMC PACS
David SherGillian Lieberman, MD
20
MR Prostate: Index PatientThe 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
Central gland
Peripheral zone
Hypointense region in right PZ
Axial
R L
Axial BIDMC PACS
BIDMC PACS
David SherGillian Lieberman, MD
21
MR Prostate, Patient 5The 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.
Sagittal Coronal
Axial
Bladder (Foley)Rectal CoilExtracapsular low-intensity mass
Bladder (Foley)Extracapsular low-
intensity massRectal Coil
Images BIDMC PACS
David SherGillian Lieberman, MD
22
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.
David SherGillian Lieberman, MD
23
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 high-
risk patients• It is always used in rising PSA following treatment
– Radioimmunoscintigraphy• Currently in use (not at BID), but its merits are still under investigation
David SherGillian Lieberman, MD
24
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
Yu KY, Hawkins RA. The prostate: Diagnostic Evaluation of Metastatic Disease. Radiologic Clinics NA; 38(1): 139-157.
AP film of pelvis showing diffuse blastic metastases
BIDMC teaching collection
David SherGillian Lieberman, MD
25
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
Yu KY, Hawkins RA. The prostate: Diagnostic Evaluation of Metastatic Disease. Radiologic Clinics NA; 38(1): 139-157.
Technetium-99m diphosphonate bone scan
showing prostate cancer metastases to:
Pelvis, femurs, spine, scapulae, humeri, and ribs
David SherGillian Lieberman, MD
26
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 pubisBladder (Invaded)
Prostate
BIDMC PACS
David SherGillian Lieberman, MD
27
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):399-401Urology 2001. 57(3):402-406
David SherGillian Lieberman, MD
28
Metastatic Workup: Prostascint
Supraclavicular lymph node(Positive biopsy)
Suspicious punctate deposition(Negative CT)
Mesenteric lymph nodes(Positive biopsy)
Known prostate cancer
59 yo man with newly diagnosed prostate cancer
Anderson RS, Eifert B et al. Radioimmunoguided surgery using indium-111 capromab to diagnose supraclavicular metastasis from prostate cancer. Urology 2000. 56(4): 669.
David SherGillian Lieberman, MD
29
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
David SherGillian Lieberman, MD
30
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
David SherGillian Lieberman, MD
31
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
Step 1: Create 3-D model from CT
This patient is a 61 yo man with a PSA .6. Cancer (Gleason 3+3) was detected by abnormal DRE.
Images from BWH Radiation Oncology
David SherGillian Lieberman, MD
32
EBRT Continued
Step 2: Beams are created to treat planning target volume
Sagittal
Coronal
Images from BWH Radiation Oncology
David SherGillian Lieberman, MD
33
Off-line dosimetryReimplantation
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
RepositionNeedle
Algorithm courtesy Rob Cormack, Ph.D.
Place seeds
DosimetricEvaluation
Dose EvaluationPlan Modification
David SherGillian Lieberman, MD
34
TRUS-Guided Brachytherapy
http://www.emedicine.com/med/topic3147.htmhttp://www.cms-stl.com/image_gallery/brachytherapy/brachytherapy_ultrsound_brachy.htm
Planning Grid3-D Dosimetry
David SherGillian Lieberman, MD
35
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.
David SherGillian Lieberman, MD
36
MR Brachytherapy Continued
Central glandPeripheral zoneSeedsNeedles
Planned isobars
3-D reconstruction
Images courtesy Rob Cormack, Ph.D.3-d reconstruction from http://splweb.bwh.harvard.edu:8000/pages/comonth/99/july/fig4.jpg
David SherGillian Lieberman, MD
37
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
David SherGillian Lieberman, MD
38
References: LiteratureAnderson 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
Clinics NA; 38(1): 139-157.
David SherGillian Lieberman, MD
39
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