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PROSTATE NEOPLASIA

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Title: PROSTATE NEOPLASIA


1
PROSTATE NEOPLASIA
  • BENIGN PROSTATIC HYPERPLASIA
  • AND
  • PROSTATE CANCER

John P. Kugler, MD, MPH COL, MC, USA
2
PROSTATE ANATOMY
  • fibromuscular tissue (30-50)
  • glandular epithelial cells (50-70)
  • peripheral zone (most cancers)
  • central zone
  • transition zone (BPH,low grade cancers)

3
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4
BENIGN PROSTATIC HYPERPLASIA
  • 17 of men age 50-59 (require Rx)
  • 27 of men age 60-69 (require Rx)
  • 35 of men age 70-79 (require Rx)
  • Similar crosscultural prevalence
  • Some genetic and racial susceptibility to symptom
    severity (autosomal dominant)
  • Diet high in saturated fats, zinc and low in
    fruits and vegetables.
  • Sedentary life style.

5
BPHProposed Etiologies
  • Reawakening of the urogenital sinus to
    proliferate
  • Change in hormonal milieu with alterations in the
    testosterone/estrogen balance
  • Induction of prostatic growth factors
  • Increased stem cells/decreased stromal cell death

6
BPHPathophysiology
  • Slow and insidious changes over time
  • Complex interactions between prostatic urethral
    resistance, intravesical pressure, detrussor
    functionality, neurologic integrity, and general
    physical health.

7
BPH Pathophysiology
  • Initial hypertrophy?detrussor decompensation?poor
    tone?diverticula formation?increasing urine
    volume?hydronephrosis?upper tract dysfunction

8
BPH SYMPTOMSObstructive and Irritative
  • Impairment of size/force of stream
  • Hesitancy
  • Intermittency
  • Terminal dribbling
  • Incomplete emptying
  • Nocturia
  • Frequency
  • Urgency
  • Dysuria

9
Other late presenting signs/symptoms
  • Abdominal/flank pain with voiding
  • Uremia?fatigue,anorexia,somnolence
  • Hernias, hemorroids, bowel habit change
  • UTIs
  • Bladder calculi
  • Hematuria

10
Other Relevant History
  • GU History (STD, trauma, surgery)
  • Other disorders (eg. neurologic, diabetes)
  • Medications (anti-cholinergics)
  • Functional Status

11
BPHClinical Findings
  • Late signs of renal failure ( eg. anemia, HTN)
  • Abdominal exam?hydronephrosis/pyelonephritis
  • GU exam? hernia, stricture, phimosis, cancer
  • DRE? a smooth enlargement, non-palpable
    nodularity with a loss of distinction between the
    lobes. A soft/firm consistency,underestimates
    enlargement, cant feel seminal vesicles

12
BPHDanger Signs on DRE
  • Firm to hard nodules
  • Irregularities, unequal lobes
  • Induration
  • Stony hard prostate
  • Any palpable nodular abnormality suggests cancer
    and warrants investigation

13
BPHClinical Evaluation
  • AUA Score to assess sx severity but NOT for DDX
  • DRE for prostate size, consistency,nodules,
    asymmetry, rectal tone and focused neuro exam
  • Abdominal/GU exam
  • UA, lytes (BUN,Creat.) PSA(interpret carefully)
  • Uroflowmetry/residual urine measure
  • Upper tract evaluation if hematuria, increased
    creatinine
  • Ultrasound
  • Cystoscopy
  • Urine cytology

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15
BPH SYMPTOMSDifferential Diagnosis
  • Urethral stricture
  • Bladder neck contracture
  • Carcinoma of the prostate
  • Carcinoma of the bladder
  • Bladder calculi
  • Urinary tract infection and prostatitis
  • Neurogenic bladder

16
BPHNatural History
  • A progressive condition (usually) with
    histological onset in the 30s and worse with age
  • A 50 yo has a 20-25 lifetime chance of needing a
    prostatectomy
  • A 40 yo who lives to 80 has a 30-40 chance of
    prostatectomy
  • But these numbers will change with new medical Rx
    and one third of patients improve on their own
  • Higher initial PSAs predict faster growth and
    higher risk of acute urinary retention

17
BPH TREATMENT INDICATIONSAbsolute vs Relative
  • Severe obstruction
  • Urinary retention
  • Signs of upper tract dilatation and renal
    insufficiency
  • Moderate symptoms of prostatism
  • Recurrent UTIs
  • Hematuria
  • Quality of life issues

18
ONE POSSIBLE APPROACH(use cautiously)
19
BPH TREATMENTNON-SURGICAL
  • Watchful waiting, AUA score own.
  • Herbal Phytotherapy (eg. Saw Palmetto)
  • Alpha-1-adrenergic antagonists (terazosin,doxazosi
    n,tamsulosin,alfuzosin)
  • 5-Alpha-reductase inhibitors (finasteride,dutaster
    ide)
  • Combination Rx most effective for most severe.
  • Medical Rx has likely reduced Medicare claims for
    BPH surgery by 50.

20
BPH TREATMENTSurgical
  • Indicated for AUA score 16
  • Transurethral Prostatectomy(TURP) 18 morbidity
    with .2 mortality. 80-90 improvement at 1 year
    but 60-75 at 5 years and 5 require repeat TURP.
  • Transurethral Incision of Prostate (TUIP) less
    morbidity with similar efficacy indicated for
    smaller prostates.
  • Open Prostatectomy indicated for glands 60
    grams or when additional procedure needed for
    suprapubic/retropubic approaches

21
BPH TREATMENTNew Modalities
  • Minimally invasive (Prostatic Stents,TUNA,TUMT,
    HIFU,Water-induced Thermotherapy)
  • Laser prostatectomy (VLAP,ILC,CLAP,TULIP,HoLRP)
  • Electrovaporization (TUVP,TVRP)

22
PROSTATE CANCERIncidence/Prevalence
  • Most common cancer in men. In the year 2000, 200K
    men were diagnosed and 30K died from the disease.
  • 21 of all cancers.
  • Increased risk with age with 30 presenting
    between age 70-79 and 67 between age 80-89.
  • Slowly progressive (as a rule) low grade?good
    prognosis, high grade?poor prognosis, and
    moderate grade?variable prognosis.

23
PROSTATE CANCERPossible etiologies/risk factors
  • Age is the most important risk factor.
  • Genetic predisposition/ racial and family
    history.
  • Diet risk high animal fat, high zinc, low
    vegetable and low fish(omega-3 fatty acids)
    intake, low selenium intake, low fruit, low
    vegetable intake.
  • Hormonal risk high testosterone, high insulin,
    and high insulin-like growth factor.
  • Low UV light exposure, high pesticide exposure.
  • No increase in risk with BPH or vasectomy.
  • ? Protection from ASA, statins.

24
PROSTATE CANCERScreening
  • DRE can detect tumors in the posterior and
    lateral aspects of the gland. Can detect
    extension. Accuracy depends on experience of
    examiner.
  • PSA must be interpreted in clinical context,
    higher sensitivity and lower specificity than
    DRE.
  • Referral for TRUS and/or sextant biopsy if DRE
    or PSA abnormal.
  • PPV for PSA 4 or DRE is 30.
  • Screening is controversial. No consensus.
    Morbidity and mortality data inconclusive.
    Informed discussion with patient is essential.

25
Prostate Cancer Screening ACP Discussion Points
  • Prostate cancer is an important health problem.
  • The benefits of one-time or repeated screening
    and aggressive treatment of prostate cancer have
    not yet been proven.
  • DRE and PSA measurements can have both
    false-positive and false-negative results.
  • The probability that further invasive evaluation
    will be required as a result of testing is
    relatively high.
  • Aggressive therapy is necessary to realize any
    benefit from the discovery of a tumor.

26
Prostate Cancer Screening ACP Additional
Discussion Points
  • A small but finite risk for early death and a
    significant risk for chronic illness,
    particularly with regard to sexual and urinary
    function, are associated with these treatments.
  • Early detection may save lives.
  • Early detection and treatment may avert future
    cancer-related illness.

27
Prostate Cancer Screening and Treatment(the key
question)
  • is cure possible in those for whom it is
    necessary, and is cure necessary in those for
    whom it is possible?
  • Dr. Willet Whitmore, 1990

28
AUA 2007 Annual Meeting
  • Men are presenting at a younger age and lower
    stage. We are seeing fewer and fewer biochemical
    recurrences, and when they do occur, they are
    less lethal. Thousands of papers support this.
  • Dr.. Anthony DAmico,
  • Dana Farber Cancer Center

29
Reasonable Recommendations in 2007 for Prostate
Screening
  • Yearly risk/benefit discussions for all men
    starting at age 50 who are expected to live 10
    years. For blacks and those with family hx
    start at 40-45.
  • If decision to screen yearly DRE/PSA until
    co-morbidities/age (75) limit life expectancy to
    10 yrs
  • Immediately refer if abnormal DRE or PSA7.
  • Repeat PSA between 4 -7 several weeks later and
    refer if still 4.
  • If PSA more than .75 ng/mL/year (based on last three
    measurements obtained over 12 to 24 months).

30
THE ROLE OF PSAPossible Refinements
  • Consider age and race adjustments.
  • PSA density(TRUS adjusted PSA).
  • PSA velocity (rate of change of PSA)(.75
    ng/mL/yr).
  • Free/Bound PSA values may be useful in separating
    elevations in PSA from BPH vs cancer.
  • Interval recommendations may change, depending on
    age and PSA level.

31
More PSA Refinements
  • Delay performing test 48 hours after recent
    ejaculation or local trauma and wait at least 6
    weeks after biopsy or TURP.
  • If PSA elevated wait 2-4 weeks and repeat to
    confirm. Some experts recommend antibiotics
    before repeat.

32
PROSTATE CANCERSigns
  • Stony hard prostate.
  • Hematuria, hematospermia.
  • Irregular, firm, hard nodule on DRE.
  • Signs of obstructive uropathy/Rising AUA Score.
  • Neurologic cord compression signs.
  • Pathologic fractures/Bone pain.
  • Sudden onset of erectile dysfunction, painful
    ejaculation.

33
PROSTATE CANCERDiagnosis
  • Prostate biopsy by FNA or Biopty.
  • 33-50 chance of biopsy being malignant.
  • Differential Diagnosis BPH, chronic prostatitis,
    prostatic TB, old biopsy fibrosis, prostatic
    cysts, prostatic calculi.

34
PROSTATE CANCERClinical Staging
  • DRE?size, location, volume, local extension
  • TRUS/Endorectal coil MRI?local extension
  • CT/ProstaScint Scan?pre-op pelvic node assessment
  • Pelvic Lymphadenectomy?pelvic nodes
  • Other Tumor Markers
  • PSA?highest in transition zone tumors and well
    differentiated tumors. Its greatest value is in
    detecting recurrence
  • Bone Scan?mets

35
PROSTATE CANCER STAGINGTMN Staging Gleason
Scale
  • T1 are microscopic and non-palpable
  • T2 are palpable but confined to gland
  • T3 protrude beyond the gland capsule
  • T4 are fixed and extend well beyond the gland
  • Based on tumor histology
  • Grade 1 Gleason is the most well-differentiated
  • Grade 5 is the most poorly differentiated
  • Combined scores are reported (primary
    secondary)(2-10)

36
PROSTATE CANCERTreatment Options for Clinically
Localized Disease
  • Radical prostatectomy
  • Radiation therapy (external beam or interstitial
    implantation)
  • Watchful Waiting
  • Possible hormonal therapy (ADT) is mostly used
    for locally advanced or metastatic disease.
    (Neoadjuvant ADT with Radiation may improve
    outcomes for men with intermediate/high
    pathological risk localized cancer.)

37
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38
MOST IMPORTANT TREATMENT ISSUES
  • Patients medical condition/age.
  • Gleason Grade and PSA.
  • Is it Organ Confined?/Stage.
  • Estimation of outcome for individual patient.
  • Potential side effects of treatments.
  • Greatest treatment benefit- moderate to poor
    grade cancers in younger, healthier age group.
  • Least treatment benefit- lower grade cancers in
    older, sicker age group.

39
MOST IMPORTANT POINTS FOR THE FAMILY PRACTITIONER
  • For BPH It is mostly a primary care disease for
    both diagnosis and treatment. Know the danger
    signs and when to refer.
  • For Prostate Cancer Screening and Rx may be
    controversial, but something is making a
    difference. All patients deserve an informed
    discussion about options.
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