PROSTATE NEOPLASIA

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PROSTATE NEOPLASIA

• BENIGN PROSTATIC HYPERPLASIA
• AND
• PROSTATE CANCER

John P. Kugler, MD, MPH COL, MC, USA
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PROSTATE ANATOMY

• fibromuscular tissue (30-50)
• glandular epithelial cells (50-70)
• peripheral zone (most cancers)
• central zone
• transition zone (BPH,low grade cancers)

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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.

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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

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BPHPathophysiology

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

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BPH Pathophysiology

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

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BPH SYMPTOMSObstructive and Irritative

• Impairment of size/force of stream
• Hesitancy
• Intermittency
• Terminal dribbling
• Incomplete emptying

• Nocturia
• Frequency
• Urgency
• Dysuria

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Other late presenting signs/symptoms

• Abdominal/flank pain with voiding
• Uremia?fatigue,anorexia,somnolence
• Hernias, hemorroids, bowel habit change
• UTIs
• Bladder calculi
• Hematuria

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Other Relevant History

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

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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

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BPHDanger Signs on DRE

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

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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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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

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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

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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

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ONE POSSIBLE APPROACH(use cautiously)
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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.

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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

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BPH TREATMENTNew Modalities

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

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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.

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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.

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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.

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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.

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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.

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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

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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

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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).

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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.

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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.

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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.

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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.

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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

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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)

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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.)

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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.

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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.