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


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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)


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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

http://education.scd.yahoo.com/reference/gray/263.html


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Prostate AnatomyLobar Anatomy Zonal Anatomy

Coakley FV, Hricak H. Radiologic Anatomy of the Prostate. Radiologic Clinics NA; 38(1): 15-30.


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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


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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


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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.


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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.


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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

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• 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

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D’Amico A. Combined-modality staging for localized adenocarcinoma of the prostate. Oncology; 15(8):1049-59.


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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)


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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.


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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


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TRUS: Prostate Cancer, Patient 2TUR Defect

Hypoechoic noduleGland volume: 25 cc

Central gland

Hypoechoic nodule


Axial

Sagittal

R L


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TRUS: Prostate Cancer, Patient 3Central gland

Peripheral zone

Hypoechoic noduleGland volume: 18 cc

Seminal vesicles


Axial

Axial

R L

R L


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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


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• 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.


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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


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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


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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


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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


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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


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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.


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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


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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


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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


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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


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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


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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.


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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


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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


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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


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EBRT Continued

Step 2: Beams are created to treat planning target volume

Sagittal

Coronal

Images from BWH Radiation Oncology


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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


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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

http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=\websites\emedicine\med\images\Large\704med3147-01.jpg&template=izoom2

http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=\websites\emedicine\med\images\Large\811med3147-03.jpg&template=izoom2


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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.


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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

http://splweb.bwh.harvard.edu:8000/pages/comonth/99/july/fig4.jpg


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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


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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.


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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

Documents

Prostate Cancer: Imaging in Diagnosis and Treatment