Prostate Cancer Management and Imaging

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Prostate CancerManagement and Imaging

• Robert Wagner, MD, FACNP
• Loyola University Medical Center
• Nuclear Medicine

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Anatomy
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Anatomy
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Anatomy
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Physiology

• Secretes prostatic fluid
• Contains citric acid, calcium, acid phosphate,
  clotting enzyme, and a profibrinolysin.
• Initially creates a coagulum when mixed with the
  fluid from the seminal vesicles.
• Dissolves the coagulum over 15-20 minutes after
  which the sperm become highly motile.
• Neutralizes the acid pH of the seminal vesicle
  fluid and the vaginal fluids.

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Prostate Tumors

• Benign Prostatic Hypertrophy (BPH)
• Benign
• Prostate Cancer
• Most frequently adenocarcinoma (gt95)
• Many men die with prostate cancer, not of it.
• Is cure necessary in those for whom it is
  possible?
• Is cure possible in those for whom it is
  necessary.
• Willet F. Whitmore, MD

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Benign Prostate Hypertrophy

• Incidence
• Rare before 40
• 50 in males 40 to 80 years old
• 75 in males gt80
• Size
• 2 grams at birth
• 20 grams by age 20, stable until about 45
• Growth after 45 is mainly periurethral

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Benign Prostate Hypertrophy

• Symptoms
• Obstruction - insidious onset
• Nocturia - from increased residual urine
• Hematuria - from straining
• Acute retention - from distended bladder
• Hernia or hemorrhoids - from straining
• Treatment - TURP or open prostatectomy

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Prostate Cancer - Incidence

• 1993 - 165,000 new cases diagnosed.
• 1996 - 318,000 new cases diagnosed.
• Rare below age 50
• Not seen in eunuchs
• Testosterone administration does not increase
  incidence
• At autopsy 12-46 of men have it (1/3 clinical)

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Prostate Cancer - Symptoms

• Look familiar?
• Obstruction - insidious onset
• Nocturia - from increased residual urine
• Hematuria - from straining
• Acute retention - from distended bladder
• Hernia or hemorrhoids - from straining
• Hemospermia?

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Prostatic Specific Antigen

• More sensitive than bone scan
• Age breakdown of normals
• 40 - 49 0.0 - 2.5
• 50 - 59 0.0 - 3.5
• 60 - 69 0.0 - 4.5
• 70 - 79 0.0 - 6.5
• PSA density - ratio of PSA to prostate volume
• PSA Velocity - rate of increase of PSA
• Free and Bound PSA

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The Dilemma

• We know that the disease is present
• We dont know where it is!
• Assumptions
• it is only in prostate gland
• it has not spread
• after therapy, rising PSA could mean that its
  anywhere

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Imaging of Prostate Cancer

• Ultrasound - mainly used for biopsy assistance
• Bone scan - highly sensitive for spread to bone
• MRI CT - Relies on size of lymph nodes.
• Highly variable sensitivity ranging from 0 to
  100.
• Lymph nodes enlarged for many reasons
• We need a better way to find prostate cancer

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Imaging - Need for a Better Agent

• What to do when postoperative PSA rises? PSA
  Failure
• Risk of metastatic disease
• no lymph nodes - 31 at 10 years
• one or more nodes - 83 at 10 years
• Periaortic nodal involvement present in 52 of
  patients without pelvic node involvement (autopsy
  study)

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Prostate Cancer - Diagnosis
Rectal Exam
PSA gt4
Follow with DRE and PSA
-
-

No Rx
TRUS - sextant Needle biopsy

Follow with DRE and PSA
PSA gt 10 or Sympt. - Bone Scan

-
Hormonal Rx
Hormonal Rx
PSA gt 20


Surgery
-
Laparoscopic LND

-
-
Surgery or RT
Intraop. Lymphadenectomy
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A Possible Solution

• Prostate cancer cells are different from normal
  prostate cells.
• Certain receptors are more abundant in prostate
  cancer than in normal prostate.
• If we can find the receptors, we can find the
  sites of likely prostate cancer.
• We need to find the key that fits the receptor!

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Immunoscintigraphy

• Relatively little published data
• Sensitivity - 55
• Specificity - 85
• Detection NOT related to PSA level
• May be useful in PSA failure patients
• Possible preoperative use in patients with PSA
  gt20
• Best for soft tissue, for bone use a bone scan.

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Some Important Points

• Antibody - a protein that binds to another
  protein
• Antigen - The specific site that the antibody
  attaches to.
• Antigen-Antibody reaction
• Very specific
• Nonreversible

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What are Monoclonal Antibodies?
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Labeling the Antibody

In111
In111
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Radioactive Monoclonal Antibodies

• By making the monoclonal antibody radioactive, we
  can follow where the material goes.
• If the radiation is there, the antibody is there.
  If the antibody is there, then the prostate
  cancer is probably there.

In111
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Problems with Antibodies

• They are proteins created in mice - may cause
  allergic reactions
• Only a small amount reacts with the cancer
• Liver, GI tract and bladder activity
• Takes days to accumulate enough in the cancer
• Requires expensive radioactive materials

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What is HAMA?

• HAMA - Human Anti Mouse Antibody
• Prostascint is a murine antibody - foreign
  protein
• Foreign proteins can stimulate antibody
  production
• HAMA may interfere with other murine tests such
  as CEA, PSA, Oncoscint and future Prostascint
  studies.
• In practice HAMA appearance is rare and
  transient.

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HAMA Effect on Antibody
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Prostate Cancer - Mechanism of Spread
Four types of spread in cancer - First three
occur in prostate cancer
Direct
Hematologic
Lymph Nodes
Coelomic
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Prostate Cancer - Staging
T1a
T1b
T1c
T2a
T2b
T2c
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Prostate Cancer - Staging
T3a
T3b
T3c
T4
N1
M1
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Prostate Cancer - Staging

• Gleason Staging
• A pathological staging describing the
  differentiation.
• Well differentiated, 2 - 4
• Moderately differentiated, 5 - 7
• Poorly differentiated, 8 - 10

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Loyola Experience

• 126 patients
• PSA at time of test ranged from 0.1 to 177
• Negative -37 (29), Positive - 89 (71)
• PSA gt20 more likely abnormal
• 54 showed local recurrence
• 50 showed nodal disease

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Loyola Results

• Only 24 patients had biopsies
• Positive Scan in bed 5 - Positive Bx - 4 (80)
• 7 Positive in LN only - 6 negative in bed, 1
  susp.
• 10 Negative bed - 4 positive on biopsy

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Based on Results of Biopsy

• When scan is positive in bed
• True Positive - 80
• False Positive - 20
• When scan is negative in bed
• True negative - 60
• False negative - 40

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Prostascint Scan - Economics
Radiopharmaceutical Antibody
750.00 In-111 450.00 Camera Time
6 hours _at_ 300/hour 1,800.00 Total cost
excluding technologist time 3,000.00
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Normal Study

• Age 60
• Prostatectomy 4/95, Gleason 33, T1cN0M0
• Postop PSA 0.0, NED
• PSA now rising to 0.6
• Imaging None

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Normal Study
Day 0
Day 4
Day 5
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Bed, Peri-aortic and Peri-iliac

• Age 69
• Prostatectomy 4/95, Gleason 34, T3aNxM0
• Postop PSA 0.0, NED
• PSA now rising to 0.3
• Imaging None

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Bed, Peri-aortic and Peri-iliac
Day 0
Day 4
Day 5
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Bed, Peri-aortic and Peri-iliac
Day 0
Day 4
Day 5
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Distant Spread

• Age 57
• Prostatectomy 8/92, Gleason 32, T3aN0M0
• Postop PSA 0.0, NED
• PSA now rising to 1.0
• Imaging
• CT-? Left iliac bone
• MRI - ? Left iliac marrow
• Bone Scan - ? SI joint, metastasis vs. DJD

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Distant Spread
Day 0
Day 4
Day 5
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Distant Spread
Day 4
Day 5
Result Metastatic disease to mesenteric and
supraclavicular nodes. Residual disease in
prostate bed.
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Spread to Nodes

• Age 69
• Prostatectomy 4/95, Gleason 34, T3aNxM0
• Postop PSA 0.0, NED
• PSA now rising to 0.3
• Imaging None

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Spread to Nodes
Day 0
Day 4
Day 5
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An Interesting Case
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An Interesting Case
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An Interesting Case