Carcinoma of Prostate: issues of screening 2005

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Carcinoma of Prostate issues of screening 2005

• David R. Rudy, MD,MPH
• Professor in Chair, Family and Preventive
  Medicine
• Chicago Medical School/ RFUMS
• Preventive Medicine MTD 601

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Relative significance of Prostate Ca

• Tumor Incidence Cause specific
  mortality
• Lung 172,570 163,510
  MF 5545
• CRC 145,290 56,290
• Breast 212,930 40,870
• Prostate 232,090 30,350 Jemal
  A, Tiwari RC, Murry T, Ward E , Samuels A,
  TiwariRC, Ghafoor A, Feuer EJ, Thun M Cancer
  Statistics, 2005. CA Cancer J. for Clin 2005
  55(1) 10-30

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Case mortality prostate Ca

• Prostate Ca deaths/US 2002 30,350 incidence/
  US 232,090 13 compare to 21 1998

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Ca Prostate burden of suffering 1(epidemiology,
incidence)

• Most common cancer in males (and pop.) second
  cause cancer death (men) after lung
• Incidence 147.6/100,000/yr males),
  1000/100,000/yr by age 80 28,900 deaths
• 189,000 new expected US 2002spurious increase
  due to increased screening during the 1980s (lead
  time bias) Jemal A, et al Cancer Statistics,
  2002. CA - Cancer Journ Clin. 2002 52(1) 23-45

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Ca Prostate burden of suffering 2(mortality)

• 15.7 /100,000/year mortality (1998)
• Case mortality increased nearly 20 from 1976
  (22.1) to 1994 (26.0), possibly due to
  increasing life expectancy.
• Cause of mortality in 3.6 (i.e. lifetime risk of
  dying of Ca prostate, comparable to breast Ca
  deaths for women)

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Ca Prostate burden of suffering 3(geography,
ethnicity)

• African-Americans lifetime death risk is 66
  higher in African Americans than white Americans
  (4.5 vs 3.6), though lifetime incidence is only
  mildly higher than in whites (18.8 vs 18.5)

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Ca Prostate

• Pathophysiology multicentric carcinoma of
  varying aggressiveness increasingly incident and
  prevalent decreasingly aggressive with age.
• Causation incidence directly related to
  testosterone production. 2ndy causes may
  include inadequate vegetables/fruit, vitamins D,
  A also obesity.

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Ca Prostate presentation (how discovered) (1)

• Prostatism (symptoms of obstruction), (Causes of
  prostatism BPH, prostatitis, Ca)
• or finding a (stony hard palpable) nodule on DRE
  50 have metastases
• asymmetrical DRE finding 50 have Ca
• bone metastases
• or screened w/ elevated PSA.

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CA prostate presentation 1A

• If PSA 4ng/mL once, 66 are organ confined
  nearly 75 if screened by serial determinations
  for rate of rise, i.e. latter more sensitive
  i.e., going from 1 ng/mL/yr.

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Prostatism

• the syndrome of urinary obstruction of varying
  degrees
• Nocturia, urgency, hesitancy, decreased size of
  stream susceptibility to acute retention
• Causes BPH, prostatitis, carcinoma

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Ca Prostate presentation (2)staging

• A non-palpable (always confined to one
  lobe)
• B palpable, confined to capsule
• C penetration of capsule, to seminal vesicles
  or bladder
• D lymph node involvement
  D1 without distant mets D2 distant
  mets, e.g. bone, lung

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Ca Prostate presentation (3)Work-up

• PSA height correlates roughly with stage (see
  Table III - 6)
• IVP to r/o involvement of ureters, kidneys
• Cystoscopy to r/o bladder (contiguous) involvement

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Ca Prostate presentation (4)Work-up

• Chest XR to r/o lung (i.e. distant) metastases
• Staging exploration lymphadenectomy (as many as
  2/3 of cases initially diagnosed as stages A,B
  may become C or D after lymph exploration)

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Therapeutic approaches prostate Ca

• Prostatectomy
• Irradiation
• Hormone (orchiectomy/estrogen)

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Ca prostate treatment 1Organ confined

• Patient
  Radical prostatectomy
• Patient / 70 y.o., life expectancy Radiotherapy. Prognosis same as surgery for
  the first 10 years
• Patients / 70 y.o. with decreased life
  expectancy or w/ small, low grade cancer
  Watchful waiting (Naitoh J et al
  AFP 1998 571131-39)

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Survival Ca Prostate

• 78 overall survival Journal CA, 43(1) (only
  1/380 with histologic dx Ca prostate will die of
  it)
• Stage A 87
• Stage B (5-10 of total) 81
• Stage C 65
• Stage D 30 CA 1993 43(2)

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Ca Prostate prevalence in different settings

• 1 in a primary care practice
• 23 in a urologists practice
• 33 of men over the age of 50 50 in 70 y.o. 70
  by 80 y.o. (autopsy studies, i.e. indolent)
  (Guide to Clinical Preventive Services, 1989)

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Ca Prostate burden of suffering 6(geography,
ethnicity)

• -much less frequent in Asians.
• Japanese men have less Ca prostate but
  Japanese-American mens rates approximate those
  of other American men.

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Pathophysiology 1

• Carcinoma of prostate produces increased serum
  PSA (normal upper limit 4.0 ng/mL, rising
  normally with age or size of gland as in BPH
• PSA elevation is lacking in 20 of cases (but
  less if rate if rise or proportion of bound PSA
  are considered)

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Pathophysiolgy 2

• Ca exists in proportion to proportion of BOUND
  PSA.
• Corollary PSA in carcinoma of prostate occurs in
  lesser proportion as FREE form (unbound).
• a cutoff of sensitivity, 18 specificity (avoid bx in 18
• Cutoff of allows 95 sensitivity, 20 specificity
  Cataloña J.A.M.A. 1997 277 1452-55

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Dx 3 PSA sens. ( 4.0 ng/mL)by stage of
prostate cancer

• Stage A
  38.0
• Stage B
  52.2
• Stage C
  68.4
• Stage D
  79.9
  from USN
  Hosp Great Lakes Lab 1997
  (Table III - 6, Syllabus

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Ca prostate screening/diagnosis 1 PSA

• PSA elevation ( 4ng/mL) is /80 sensitive for
  prostate cancer, and 90 specific .
• Thus, with average risk there are many false
  positives
• Thus, PSA not an ideal screen test

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Ca prostate diagnosis 2 PSA

• Normal PSA defined according to age group. (See
  Table III-7)
• 40-49 years 0.0-2.5 ng/mL (median 0.7)
• 50-59 years 0.0-3.5 ng/mL (median 1.0)
• 60-69 years 0.0-4.5 ng/mL (median 1.4)
• 70-79 years 0.0-6.5 ng/mL (median 2.0)
  (Oesterling et al J.A.M.A. 1993 270 860-64)
• Another criterion rise PSA 0.7 ng/mL/yr

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Ca prostate Dx

• Percent of free PSA
• Free PSA
• Free PSA 25 cuts risk to 8
• Free PSA measurement is most useful when total
  PSA 4 -10 ng/mL Cataloña et al Patient Care
  1998 Sept 30 58-83

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Ca prostate diagnosis 4Spurious causes of PSA
elevation

• cystoscopy, prostate biopsy, prostate massage,
  prostatitis, urethral instrumentation
• large volume of gland as in BPH

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Criteria for screenability satisfied?

• 1. Condition has significant effect on life (yes)
• 2. Treatment available (sort of)
• 3. Asymptomatic period of diagnoseability (yes)
• 4. Treatment in asymptomatic yields result
  superior to delaying until symptoms appear
  (maybe)
• 5. Tests of reasonable cost- sensitivity and
  specificity appropriate for population risk (not
  perfect)
• 6. Incidence sufficient to justify cost (yes)

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Screening recommendations for prostate Ca,
conservative view

• ACS (June 6, 1997) and NCI annual DRE from the
  age of 50 if life expectancy of at least 10
  years)
• at 45 years of age for those at high risk ( 2
  1st degree relatives with prostate cancer,
  African-American).
• Urological association same except start at 40
  y.o.

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Ca prostate Screening, liberal (aggressive) view

• PSA screening annually recommended when
  
  1. male 50 y.o., 2. 40 y.o. African American male
  3. male 35 y.o. if 1st degree F.H. Ca
  prostate x 3 at early ages
• If 2.5-
• If 4 -10, obtain free PSA if 25, biopsy

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Ca prostate Dx 5 Indications for Biopsy

• Abnormal DRE
• Elevated PSA 4
• PSA for age (e.g. 2.5 for 3.5 for
  
• Percent of free PSA
• Rate of rise with age 0.7/yr)

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Ca prostate Dx 5 A Other Indications for Biopsy

• PSA 4 -10 ng/mL with free PSA
• PSA 10 ng/mL!
  Cataloña et al Patient Care 1998 Sept 30 58-83

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Ca prostate definitive diagnosis

• Transrectal ultrasonic study
• Transurethral resection biopsy
• Transrectal biopsy

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Therapy of Ca Prostate 1 stages A or B

• Patient
  Radical prostatectomy
• Patient / 70 y.o., life exp 10 years or
  Radiotherapy. Prognosis same as surgery for
  the first 10 years
• Patients / 70 y.o. with decr. life expectancy
  or w/ small, low grade cancer
  Watchful waiting

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Therapy of Ca Prostate 2 Stages C or D

• Testosterone deprivation i.e., orchiectomy,
  estrogen therapy
• Irradiation of prostate (49)
• or of pelvic nodes f/b prostate (45.5)

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Complications of Radical Prostatectomy 1
Impotence

• 40-50 years 0
• 51-60 years 45
• 61-70 years 57
• 70 years 100

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Complications of Radical Prostatectomy 2
Incontinence

• None 81.5
• Mild (one pad/d) 14
• Moderate (multiple pads) 3
• Severe (total) 1.5