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Carcinoma of Prostate: issues of screening 2005

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CA: Cancer J. for Clin 2005; 55(1): 10-30. Case mortality prostate Ca ... PSA elevation ( 4ng/mL) is =/ 80% sensitive for prostate cancer, and 90% specific ... – PowerPoint PPT presentation

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Title: Carcinoma of Prostate: issues of screening 2005


1
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

2
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

3
Case mortality prostate Ca
  • Prostate Ca deaths/US 2002 30,350 incidence/
    US 232,090 13 compare to 21 1998

4
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

5
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)

6
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)

7
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.

8
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.

9
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.

10
Prostatism
  • the syndrome of urinary obstruction of varying
    degrees
  • Nocturia, urgency, hesitancy, decreased size of
    stream susceptibility to acute retention
  • Causes BPH, prostatitis, carcinoma

11
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

12
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

13
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)

14
Therapeutic approaches prostate Ca
  • Prostatectomy
  • Irradiation
  • Hormone (orchiectomy/estrogen)

15
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)

16
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)

17
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)

18
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.

19
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)

20
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

21
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

22
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

23
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

24
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

25
Ca prostate diagnosis 4Spurious causes of PSA
elevation
  • cystoscopy, prostate biopsy, prostate massage,
    prostatitis, urethral instrumentation
  • large volume of gland as in BPH

26
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)

27
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.

28
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

29
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)

30
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

31
Ca prostate definitive diagnosis
  • Transrectal ultrasonic study
  • Transurethral resection biopsy
  • Transrectal biopsy

32
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

33
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)

34
Complications of Radical Prostatectomy 1
Impotence
  • 40-50 years 0
  • 51-60 years 45
  • 61-70 years 57
  • 70 years 100

35
Complications of Radical Prostatectomy 2
Incontinence
  • None 81.5
  • Mild (one pad/d) 14
  • Moderate (multiple pads) 3
  • Severe (total) 1.5
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