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Prostate Cancer screening

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Prostate Cancer screening Powered By Docstoc
					  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
                Relative significance
                   of Prostate Ca
   Tumor               Incidence             Cause specific
                                                mortality
   Lung               172,570                  163,510
                                             M:F =55%:45%
 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
  Case mortality prostate Ca

  Prostate Ca deaths/US 2002 30,350 ÷
incidence/ US 232,090 = 13%; compare to
            21% 1998
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 2002:spurious
  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
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)
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%)
              Ca Prostate
 Pathophysiology: multicentric carcinoma of
  varying aggressiveness; increasingly
  incident and prevalent; decreasingly
  aggressive with age.
 Causation: incidence directly related to
  testosterone production. 2nd’y causes may
  include inadequate vegetables/fruit,
  vitamins D, A; also obesity.
    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.
     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.
            Prostatism:

 the syndrome of urinary obstruction
  of varying degrees
 Nocturia, urgency, hesitancy,
  decreased size of stream;
  susceptibility to acute retention
 Causes: BPH, ± prostatitis,
  carcinoma
    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
  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
    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)
Therapeutic approaches prostate
              Ca
Prostatectomy
Irradiation
Hormone
 (orchiectomy/estrogen)
        Ca prostate treatment 1:
            Organ confined
 Patient < 70 y.o., life exp. 10 years or >:
  Radical prostatectomy
 Patient =/> 70 y.o., life expectancy < 10
  years : 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; 57:1131-39)
         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)]
      Ca Prostate: prevalence in
          different settings
 1%  in a primary care practice
 23% in a urologist’s 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)
Ca Prostate: burden of suffering 6
          (geography, ethnicity)

 -much  less frequent in Asians.
 Japanese men have less Ca
  prostate but Japanese-American
  men’s rates approximate those
  of other American men.
          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)
                    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 < 27% free PSA 2.6-4.0 allows 90%
    sensitivity, 18% specificity (avoid bx in 18%:
   Cutoff of < 25% in patients with 4 -10 ng/mL
    allows 95% sensitivity, 20% specificity:
    Cataloña: J.A.M.A. 1997; 277: 1452-55
    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]
        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
    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
                 Ca prostate Dx :

 Percent      of free PSA < 27%
 Free PSA < 10% carries 56% risk of
  carcinoma
 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
        Ca prostate diagnosis 4:
 Spurious causes of PSA elevation:

 cystoscopy, prostate biopsy,
  prostate massage, prostatitis,
  urethral instrumentation;
large volume of gland as in BPH
    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)
 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.
    Ca prostate Screening, liberal
         (aggressive) view:
 PSA screening annually recommended
  when:
  1. male> 50 y.o., < 75 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- < 4- ng/mL, check q 6 mo.
 If 4 -10, obtain free PSA; if ≤ 25, biopsy
Ca prostate Dx 5: Indications for
            Biopsy:
 Abnormal   DRE
 Elevated PSA [> 4]
 PSA for age (e.g. > 2.5 for < 50 y.o.; >
  3.5 for < 60 y.o.)
 Percent of free PSA {< 27%}
 Rate of rise with age{≥ 0.7/yr})
    Ca prostate Dx 5 A: Other
     Indications for Biopsy:
 PSA 4 -10 ng/mL with free PSA
  < 25%
 PSA > 10 ng/mL!
 Cataloña et al: Patient Care 1998; Sept 30: 58-83
Ca prostate definitive diagnosis:

 Transrectal ultrasonic study
 Transurethral resection biopsy
 Transrectal biopsy
 Therapy of Ca Prostate 1: stages
             A or B
 Patient < 70 y.o., life exp 10 years or >:
  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
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%)
    Complications of Radical
   Prostatectomy 1: Impotence
 40-50 years: 0 %
 51-60 years: 45%
 61-70 years: 57%
 > 70 years: 100%:
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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