Transcript PROSTATE CANCER - the Bedford Foundation

PROSTATE CANCER - 2012
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241,740 new cases
29 % of all new male cancer cases
28,170 deaths
Lifetime risk of prostate cancer 1:5
DEATHS
INCIDENCE
2012 Estimates – American Cancer Society
# of patients
PROSTATE CANCER
350,000
300,000
250,000
200,000
150,000
100,000
50,000
0
New Cases
Deaths
2012
2010
2008
2006
2004
2002
2000
1998
1996
1994
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Year
PROSTATE CANCER
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30% of men > 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
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.
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
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
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 E…Messing EM. Cancer Online (July 30, 2012)
PLCO - CaP Screening Trial
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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.
Incidence of
CaP
CaP Deaths
Screened
Control
(38,343 pts.)
(38,350 pts.)
116
95
(2820 cancers) (2322 cancers)
2.0 (50 deaths) 1.7 (44 deaths)
Andriole GL et al NEJM 360:1310, 2009.
PLCO - CaP Screening Trial
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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 360:1310, 2009.
EORTC Randomized CaP
Screening Study
• 162,387 men age 55-69 years
• Screened every 4 years; cutpoint PSA > 3.0
• * 20% reduction in CaP deaths ( p = 0.04)
Findings
Incidence CaP
Screened
(72, 890 pts)
8.2%
Control
(89,353 pts)
4.8%
CaP Deaths
214*
326*
Schroder FH et al. NEJM 360:1320, 2009.
EORTC Randomized CaP
Screening Study - Conclusions
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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 <0.001)
Schroder FH et al. NEJM 360:1320, 2009.
Göteborg CaP Screening Study
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Randomized population-based 1:1 (59 y/o)
20,000 men PSA testing every 2 years
Median followup 14 years
Dx CaP: 12.7% vs 8.2% (p < 0.0001)
CaP deaths 0.56 in screened men (p=0.002)
293 screened; 12 dx to prevent 1 CaP death
Hugosson J et al . Lancet Oncol 11: 725, 2010.
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
12-core Biopsy Technique
Gleason Pathologic
Grading System
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Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The Prostate.
Philadelphia, Pa: Lea & Febiger; 1977:171-197.
Clinical T(umor) Stage
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T1a/b – Incidental CaP after TURP
T1c - Discovered by PSA; no nodule
T2a – Prostate nodule < ½ of 1 side
T2b – Prostate nodule > ½ of 1 side
T2c – Prostate nodules both sides
T3a – CaP through capsule 1 or both sides
T3b – Seminal vesicle invasion
RISK STRATIFICATION
Risk Grp.
Low
PSA
Gleason
T-stage
10 &  7
& T1c/T2a
Intermed. 10-20
High
or
7
or
>20 or 8-10 or
or > 2 ng in past year
T2b
T2c /+
PROSTATE CANCER
Mgt: LOCALIZED CaP
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Active Surveillance
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Radical Radiation Therapy
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Radical Prostatectomy
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Factors:
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Age and health of patient
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Extent of disease
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Morbidity
Watchful Waiting - Localized CaP
Albertson PC et al. JAMA 293:2095-2101, 2005
Active Surveillance - Candidates
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> age 70-75 (?? Age 65 +)
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Intercurrent illness or comorbidities
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Gleason 3 +3 on few biopsies
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Low stage (T2 or <)
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Low PSA with slow rise on serial study
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Understand need for periodic biopsies
Watchful Waiting vs. RRP
Bill-Axelson et al NEJM 352:1977, 2005
PIVOT TRIAL: Observation
vs. Radical Prostatectomy
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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 >10 and possibly
intermediate/high risk CaP
Wilt,TJ et al. NEJM 2012; 367:203
PIVOT TRIAL: Observation vs.
Radical Prostatectomy
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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; 367:203
Open Radical Prostatectomy
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2 ½ hour operation
2 day hospitalization
Catheter x 1 week
Recovery 3-4 weeks
Palpation of prostate
http://www.orlive.com/brighamandwomens/videos
Robotic Radical Prostatectomy
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2-3 hour operation
1 day hospitalization
Catheter x 1 week
Recovery 2-3 weeks
Long learning curve (minimum 300)
No palpation of prostate
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
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Bleeding during surgery
Incontinence
Persistent erectile
dysfunction
Bowel complications
Anastomotic stricture
Recovery period – loss of
human capital
Eastham JA, Scardino PT. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders;
2002:3080,3091,3126.
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
D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3152.
Zelefsky MJ, et al. J Urol. 2001;166:876-881.
Intensity Modulated RT (IMRT)
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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
D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3155.
Zelefsky MJ, et al. J of Urol. 2001;166:876-881.
Brachytherapy
Advantages
Disadvantages
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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
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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)
D’Amico, AV, et al. Campbell’s Urology. 8th ed. Philadelphia, Pa: WB Saunders; 2002:3158.
Grimm PD, et al. Int J Radiat Oncol Biol Phys. 2001;51:31-40.
Beyer DC, et al. Radiother Oncol. 2000;57:263-267.
Blasko JC, et al. Radiother Oncol. 2000;57;273-278.
MGT. of Localized CaP
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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