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PROSTATE CANCER - 2012

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PROSTATE CANCER - 2012 241,740 new cases ... Screening for prostate cancer should be actively discouraged Committee of primary care physicians; ... – PowerPoint PPT presentation

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Title: PROSTATE CANCER - 2012


1
PROSTATE CANCER - 2012
  • 241,740 new cases
  • 29 of all new male cancer cases
  • 28,170 deaths
  • Lifetime risk of prostate cancer 15

2
2012 Estimates American Cancer Society
INCIDENCE
DEATHS
3
PROSTATE CANCER
4
PROSTATE CANCER
  • 30 of men gt 50 years old have CaP at autopsy
  • Lifetime risk of malignancy in 50y/o - 42
  • Lifetime risk of CLINICAL CaP - 19
  • Risk of dying from CaP - 2.9
  • UNIQUE DISCREPANCY OF PREVALENCE versus CLINICAL

5
U.S. Preventive Services Task Force(Draft
report 10/11/2011)
  • Recommends against screening for prostate
    specific antigen
  • Moderate or high certainty that no net benefit
    or harms outweigh benefits
  • Grade D recommendation discourage the use of
    this service- applies to all healthy men.

6
U.S. Preventive Services Task Force(Draft
report 10/11/2011)
  • Relied heavily on meta-analyses combining high
    and low quality evidence
  • Used overall mortality rather than cancer
    specific mortality
  • Considered only intention to treat
  • Did not consider risk stratification or longer
    duration of followup

7
USPSTF on Prostate Ca Screening FINAL REPORT
  • Class D recommendation Screening for prostate
    cancer should be actively discouraged
  • Committee of primary care physicians headed
    by pediatrician
  • No Urological or Oncology consultants
  • Same group No mammograms age 40-50

Promulgated May, 2012
8
Effect of USPSTF Recommendation on Metastatic
Prostate Ca
  • SEER data 1983-1995 vs. 2006-2008
  • Adj. for age, race, geographic variation
  • Computed of men who presented w/ M1 in
    SEER 9 registries area in 2008
  • Expected/observed ratio M1 in 2008 3.1
  • If USPSTF rec. applied to US population
  • 25,000 vs. 8000 CaP pts. with metastases

Scosyrev EMessing EM. Cancer Online (July 30,
2012)
9
PLCO - CaP Screening Trial
  • 76,693 men
  • Randomized to annual screen vs. usual practice
  • At 7-10 years, death rate low and not different

Findings per 10,000 pt. yrs. Screened (38,343 pts.) Control (38,350 pts.)
Incidence of CaP 116 (2820 cancers) 95 (2322 cancers)
CaP Deaths 2.0 (50 deaths) 1.7 (44 deaths)
Andriole GL et al NEJM 3601310, 2009.
10
PLCO - CaP Screening Trial
  • Contamination (40-52)
  • of patients pre-screened
  • Short followup for mortality
  • Wide confidence bars
  • Percent of controls with higher stage/grade

Andriole GL et al NEJM 3601310, 2009.
11
EORTC Randomized CaP Screening Study
  • 162,387 men age 55-69 years
  • Screened every 4 years cutpoint PSA gt 3.0
  • 20 reduction in CaP deaths ( p 0.04)

Findings Screened (72, 890 pts) Control (89,353 pts)
Incidence CaP 8.2 4.8
CaP Deaths 214 326
Schroder FH et al. NEJM 3601320, 2009.
12
EORTC Randomized CaP Screening Study -
Conclusions
  • High rate of overdiagnosis (8.2 vs. 4.8)
  • PSA screening reduced CaP deaths (p .04)
  • Death risk difference 0.71/1000 men
  • 1410 men screened/48 Rx to prevent 1 death
  • Benefit of screening Age 55-69 years
  • 41 reduction in adverse features (p lt0.001)

Schroder FH et al. NEJM 3601320, 2009.
13
Göteborg CaP Screening Study
  • Randomized population-based 11 (59 y/o)
  • 20,000 men PSA testing every 2 years
  • Median followup 14 years
  • Dx CaP 12.7 vs 8.2 (p lt 0.0001)
  • CaP deaths 0.56 in screened men (p0.002)
  • 293 screened 12 dx to prevent 1 CaP death

Hugosson J et al . Lancet Oncol 11 725, 2010.
14
CONCLUSIONS
  • Careful analysis SUPPORTS screening for CaP
  • Problem is overtreatment, not overdiagnosis
  • Better predictors of aggressiveness would limit
    overtreatment
  • Less morbid therapies would diminish problems
    with overtreatment
  • Controversies about prostate cancer will persist

15
(No Transcript)
16
12-core Biopsy Technique
17
Gleason Pathologic Grading System
X
X
Gleason DF. In Tannenbaum M, ed. Urologic
Pathology The Prostate.Philadelphia, Pa Lea
Febiger 1977171-197.
18
Clinical T(umor) Stage
  • T1a/b Incidental CaP after TURP
  • T1c - Discovered by PSA no nodule
  • T2a Prostate nodule lt ½ of 1 side
  • T2b Prostate nodule gt ½ of 1 side
  • T2c Prostate nodules both sides
  • T3a CaP through capsule 1 or both sides
  • T3b Seminal vesicle invasion

19
RISK STRATIFICATION
  • Risk Grp. PSA Gleason T-stage
  • Low ?10 ? 7 T1c/T2a
  • Intermed. 10-20 or 7 or T2b
  • High gt20 or 8-10 or
    T2c /
  • or gt 2 ng in past year

20
PROSTATE CANCERMgt LOCALIZED CaP
  • Active Surveillance
  • Radical Radiation Therapy
  • Radical Prostatectomy
  • Factors
  • Age and health of patient
  • Extent of disease
  • Morbidity

21
Watchful Waiting - Localized CaP
Albertson PC et al. JAMA 2932095-2101, 2005

22
Active Surveillance - Candidates
  • gt age 70-75 (?? Age 65 )
  • Intercurrent illness or comorbidities
  • Gleason 3 3 on few biopsies
  • Low stage (T2 or lt)
  • Low PSA with slow rise on serial study
  • Understand need for periodic biopsies

23
Watchful Waiting vs. RRP
Bill-Axelson et al NEJM 3521977, 2005
24
PIVOT TRIAL Observation vs. Radical Prostatectomy
  • 731 men, randomized, 1994-2002
  • Mean age 67 Intention to treat analysis
  • Median followup 10 years
  • All cause MR 47 vs. 49.9
  • CaP MR 5.8 vs. 8.4 (p 0.09)
  • ? all cause MR if PSA gt10 and possibly
    intermediate/high risk CaP

Wilt,TJ et al. NEJM 2012 367203
25
PIVOT TRIAL Observation vs. Radical Prostatectomy
  • Original goal 2000 pts
  • Median age older (67 y/o) only 50 T1c
  • VA population with ? comorbidities
  • 25 of pts. for RRP did not undergo Rx
  • 10 of pts. for obs. underwent RRP
  • Bone mets in obs. - 10 vs. 4.7

Wilt,TJ et al. NEJM 2012 367203
26
Open Radical Prostatectomy
  • 2 ½ hour operation
  • 2 day hospitalization
  • Catheter x 1 week
  • Recovery 3-4 weeks
  • Palpation of prostate

http//www.orlive.com/brighamandwomens/videos
27
Robotic Radical Prostatectomy
  • 2-3 hour operation
  • 1 day hospitalization
  • Catheter x 1 week
  • Recovery 2-3 weeks
  • Long learning curve (minimum 300)
  • No palpation of prostate

28
Radical Prostatectomy
  • Advantages
  • Definitive therapy to remove primary tumor
  • Stage dependent
  • Allows for pathological staging
  • Better prognosis determination
  • Nerve sparing
  • Psychological impact
  • Disadvantages
  • Major inpatient surgery
  • Bleeding during surgery
  • Incontinence
  • Persistent erectile dysfunction
  • Bowel complications
  • Anastomotic stricture
  • Recovery period loss of human capital

Eastham JA, Scardino PT. Campbells Urology. 8th
ed. Philadelphia, Pa WB Saunders
20023080,3091,3126.
29
External Beam Radiation Therapy (EBRT)3D
Conformal
  • Advantages
  • Efficacy equal to prostatectomy at 5 years
  • Outpatient procedure
  • More precise treatment target - less side
    effects than nonconformal
  • Painless procedure
  • Allows escalation of RT dose to 81 Gy
  • No loss in human capital
  • Disadvantages
  • Acute/chronic bowel complications
  • Incontinence
  • Persistent erectile dysfunction
  • Daily treatments for 7-8 weeks

DAmico, AV, et al. Campbells Urology. 8th ed.
Philadelphia, Pa WB Saunders 20023152. Zelefsky
MJ, et al. J Urol. 2001166876-881.
30
Intensity Modulated RT (IMRT)
  • Inverse treatment planning
  • Computer controlled RT intensity
  • Mathematical optimization technique utilized
  • Enables further delivery of minimal and maximal
    dose RT vs 3-D EBRT
  • Less rectal complications than 3-D and
    conventional EBRT
  • Allows escalation of the RT dose to 86.4 Gy
  • Limited availability

DAmico, AV, et al. Campbells Urology. 8th ed.
Philadelphia, Pa WB Saunders 20023155. Zelefsky
MJ, et al. J of Urol. 2001166876-881.
31
Brachytherapy
  • Advantages
  • Efficacy approaching that of EBRT or surgery
    (short term)
  • Procedure completed in one session
  • Outpatient procedure
  • Delivers higher doses radiation over shorter
    period of time
  • Disadvantages
  • Urinary voiding symptoms
  • Rectal discomfort
  • Edema
  • Persistent erectile dysfunction
  • Migration of seeds
  • Variability of duration of action
  • Epidural or general anesthesia
  • Unknown long-term effectiveness (10-year
    effectiveness)

DAmico, AV, et al. Campbells Urology. 8th ed.
Philadelphia, Pa WB Saunders 20023158. Grimm
PD, et al. Int J Radiat Oncol Biol Phys.
20015131-40. Beyer DC, et al. Radiother Oncol.
200057263-267. Blasko JC, et al. Radiother
Oncol. 200057273-278.
32
MGT. of Localized CaP
  • Optimal Rx of local disease controversial
  • Radical prostatectomy is the most proven method
    for long term survival
  • Quality of life is an important consideration
  • Further improvements in survival depend on
    development of effective adjuvant Rx
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