The Prostate

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The Prostate

• Robert Ball, M.D., F.A.C.S.
• Clinical Professor of Urology
• Inova Fairfax Hospital Cancer Center

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What is the Prostate

• Round organ/gland with a hole (donut)
• Lives under the bladder and is the size of a
  large walnut
• Men urinate and ejaculate through the hole
• The prostate and its associated gland the
  seminal vesicles produce the seminal fluid (only
  2 of semen is sperm)
• The prostate has two histological tissue types
• The glandular tissue which makes the prostate
  fluid
• The stromal tissue which give the gland shape and
  tone

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anatomy
prostate
rectum
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Enlarged Prostate (EP) Overview

• Prostate size ? 30 mL
• Progressive condition
• Results in varying levels of bladder outlet
  obstruction
• Major cause of urinary symptoms in older men
• Most common prostate condition

Hypertrophied detrusor muscle
Obstructed urinary flow
Roehrborn CG et al. In Campbells Urology, 8th
ed. Philadelphia, Pa Saunders 20021297?1336.
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Symptoms Associated with Enlarged Prostate (EP)

• Obstructive Symptoms
• Hesitancy
• Weak stream
• Straining to pass urine
• Prolonged micturition
• Feeling of incomplete bladder emptying
• Urinary retention

• Irritative Symptoms
• Urgency
• Frequency
• Nocturia
• Urge incontinence

Kirby RS et al. Benign Prostatic Hyperplasia.
Oxford, UK Health Press 1995.
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Anatomy
bladder
rectum

• pubis

prostate
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Prostate Cancer

• Adenocarcinoma of the Prostate
• Adeno means gland or glandular
• Carcinoma means a malignant differentiation of an
  epithelial or endothelial tissue
• Thus, the typical prostate cancer is a malignancy
  of the prostate glandular tissue
• A malignancy of the stromal tissue would be a
  sarcomavery rare and really bad

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Prostate Cancer Risk Factors

• Genetics
• One 1st degree relative 2x increased risk
• Two 1st degree relatives 5x increased risk
• Three or more 1st degree relatives 10x risk

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Prostate Cancer Risk Factors

• Diet
• High fat diet increases risk
• High levels of cadmium (tobacco and batteries)
• High levels of selenium and Vit E decrease risk

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Prostate Cancer Epidimiology

• Most common malignancy in American men
• 2nd highest incidence of male CA deaths
• 38,000 deaths per year (decreasing)
• 1/10 men will get significant CAP
• 1/3 who get CAP will die of it
• Lung CA is most lethal CA
• Colon CA is third most lethal

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Prostate Cancer Risk Factors

• Age is a disease whose prevalence increases with
  age
• Rare in men less that 40
• Common in men over age 80

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Prostate Cancer Screening

• PSA and DRE
• Yearly for most men age 50 70
• Yearly for African-Americans and all men with a
  family history of CAP at age 40-45
• Not to be done routinely after age 75 and
  certainly not indicated in men over 80
• Can be performed q 2 years with PSA lt 1.0

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Prostate Cancer Detection

• Prostate biopsy is only way to detect CAP
• Indications for biopsy
• PSA gt age specific normal
• Any abnormal DREno matter the PSA
• PSA increasing by more than 0.75 ng/dl/year over
  an 18 month period including 3 data points

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PSA Prostate Specific Antigen

• Produced only by the prostate glandular cells
• Not produced by any other cells in the body
• 33 kd serine protease that liquifies semen
• exists in free and bound states in the blood
• Relationship of free and bound serum PSA
  correlates with the risk of CAP
• - PSA serum levels can vary 10 30 during the
  day

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Prostate Cancer Detection

• Caveat about PSA
• PSA elevation is not specific for CAP
• 75 of men with a PSAgt 4.0 do NOT have CAP
• 20 of men with CAP have a PSA lt 4.0

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Molecular forms of PSA

• Most (90) of PSA bound to serum protein
  alpha-1-antichymotrypsin and alpha-2-macroglobulin
  s.
• Remainder of PSA is free floating
• The ratio of the free / free plus bound when PSA
  gt 4 gives statistical correlate to CAP risk
• If f/t gt 25 less than 6 risk CAP
• If f/t lt 10 greater than 56 risk CAP

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Age Adjusted PSA

• Age Range (years)
• 40 49
• 50 59
• 60 69
• gt 70

• Normal PSA
• lt 2.5
• lt 3.5
• lt 4.5
• lt 6.5

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Gleason Grade

• Prostate cancers are graded by the difference in
  the glandular architecture
• Dr. Gleason, a pathologist, came up with a
  numbering system to differentiate CAP
• Two numbers between 1-5 added together
• The first number is the predominate gland
• The second number is the next gland
• The total of these two numbers yields the Gleason
  grade which is s sum between 2 and 10

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Gleason Grade

• Gleason sum
• 1 1 2
• 2 2 4
• 3 2 5
• 3 3 6
• 3 4 7
• 4 3 7
• 4 4 8
• 5 5 10

• Differentiation
• Well Differentiated
• Moderately Differentiated
• Poorly differentiated

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Prostatic Intraepithilial Hyperplasia
PINDifferentiation of Cells
Cancer
PIN
Normal
cells
Low grade
Mod grade
High grade
Gleason
Grade
6
2
10
Spectrum showing cells becoming more
abnormal/different
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Stage
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Prostate Cancer Survival Statistics

• Prostate CA requires greater than 10 years to
  cause impact on survival
• However, CAP 15 year mortality 62
• Therefore patients with less than 10 year
  expected survival may not need treatment
• N.B. Patients surviving 10 years with CAP have
  60-80 risk of morbidity
• Bone pain, spinal cord injury, urinary retention,
  renal failure, lower extremity lymphedema and
  infection

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Treating CAP With Watchful Waiting

• It takes CAP at least 10 years to do its dirty
  deed
• WW appropriate if
• Life expectancy lt 10 years (older age 72-74)
• Gleason lt 2 2
• Microscopic focus of disease
• Even with above 10 risk of death by CAP

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Cryotherapy

• Freezing and thawing prostate kills tumor
• Outpatient procedure similar to brachytherapy
• Multiple hollow core probes placed with TRUSP
• Ice balls form around probes at 25 to 50 C
• Similar cure rates as radiation therapy,
  approaching 85
• Possibility of just treating prostate cancer and
  sparing the rest of the prostate in select cases-
  focal therapy
• Can be performed for primary therapy or after
  radiation treatment failures

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Radiation Therapy

• Mechanism of Tumor Kill
• The higher the dose of radiation the better the
  kill
• Ionizing radiation causes
• Destruction of DNA so cells die upon mitosis
• Superoxide reaction resulting in rupture of cell
  membrane

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External Beam Radiotherapy

• Ionizing beam of radiation pointed at prostate
• Treatment every week day for 8 weeks
• Radiation dose is limited by the collateral
  damage risks to bladder and rectum
• Conformal therapy allows increased dosages
• Is a bona fide treatment alternative,
  particularly for patients gt age 65
• Does have proven failure rate than RRP

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Brachytherapy (Seeds)

• High dose radiation delivered with seeds
• Can obtain doses 2 3 times external beam
• Best for small volume tumors Gleason lt 6
• Outpatient treatment in OR
• Limited collateral damage to bladder/rectum
• Can burn urethra
• Unable to sterilize tumor outside capsule
• Can be performed in conjunction with or as
  salvage after failed external beam RT

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Radical Prostatectomy

• Walsh nerve sparring procedure gives overall best
  chance for cure
• Cure rates correlate directly with pathologic
  grade and stage
• Complications of surgery
• E.D., incontinence, bleeding and rectal injury
• Related to surgeon experience and patient age

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Davinci Robot- Can be used for Radical
Prostatectomy (DVP)
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Comparison Old vs. New
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Metastatic disease

• CAP uses androgens as a fuel
• Removal of testosterone causes apoptosis
• Hormonal ablation effects will wane with time
• Not curative
• 95 of T is produced by Leydig cells of testis
• Under pituitary control with feed back systems
• Can remove T by
• Removing testis
• Turning off Leydig cells
• Giving female hormone estrogen (vascular risks)

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Metastatic CAP refractory to hormones

• Complete androgen blockade
• Block androgen receptor from seeing adrenal T
• Chemotherapy
• Anti-angiogenesis agents (Thalidomide)
• Taxol, etoposide, Mitoxantrone, Estramustine
• Strontium 89 for bone mets pain
• Investigational Immunotherapy
• Vaccines and gene therapy

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Recurrence After RRP

• Local recurrence
• Difficult to prove
• if surgical margin
• PSA undetectable post op
• PSA double time lt 1 year
• External beam RT /- hormone ablation

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Dr. Ball and Fairfax OR Nurses
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Dr. Simon Chung Director Robotic Surgery
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