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Prevention and Early Detection of Prostate Cancer

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Prevention and Early Detection of Prostate Cancer Ian Thompson, Jr. MD * * * * * * * * * * * * * * * * As can be seen, the risk of prostate cancer at a PSA of 3.2 ng ... – PowerPoint PPT presentation

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Title: Prevention and Early Detection of Prostate Cancer


1
Prevention and Early Detection of Prostate Cancer
  • Ian Thompson, Jr. MD

2
What is the CTRC?
  • 1 of 4 NCI-Designated Centers in Texas 66 in
    U.S.
  • Combines
  • Comprehensive, multidisciplinary care
  • Clinical Trials including Institute for Drug
    Development Phase I studies
  • Research from bench to bedside

3
The CTRC Mission
Eliminating cancer through research, prevention,
detection, and treatment.
Dr. Ian M. Thompson Director
Dr. Susan Mooberry Interim Director, IDD
Dr. Tim Huang Deputy Director
4
The CTRC Mission
Eliminating cancer through research, prevention,
detection, and treatment.
Dr. Ian M. Thompson Director
Dr. Steve Weitman New Director, IDD
Dr. Tim Huang Deputy Director
5
The NCI-Designated Cancer Center for Central and
South Texas
CTRC Campus
IDD at Texas Research Park
MARC Campus
South Texas Research Facility
Greehey Childrens Cancer Research Institute
Long Campus at the Health Science Center
6
What is an NCI-Designated Cancer Center?
  • The highest level of cancer care
  • Latest advances in cancer research
  • Cutting-edge clinical trials that are the cancer
    cures of tomorrow
  • Cancer Education from high school to PhD to the
    public
  • Outreach to underserved populations
  • Coordination of efforts to reduce the burden of
    cancer for central and South Texas

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Risk of cancer in our prostate by age
10
Prostate Cancer will be an important problem for
many years to come.
  • Aging in the U.S.-Past, Present, and Future.
    From www.census.gov/ipc/prod/97agewc.pdf.

11
Options for Control of Prostate Cancer
  • Cure the disease when it presents
    symptomatically.
  • Screen for the disease treat it when you find
    it.
  • Prevent it.

12
What happens if we wait for symptoms?
Average survival less than 4 years
13
Options for Control of Prostate Cancer
  • Cure the disease when it presents
    symptomatically.
  • Screen for the disease treat it when you find
    it.

14
A Couple of Questions
  • I suspect that if the men in the audience are
    like most US men, 75 or more of you have had a
    PSA test.
  • So, what PSA value is abnormal?

15
How did we get a PSA value of 4.0?
  • Lifetime risk of prostate cancer in 1985 8.
  • About 8 of screened men had PSA gt 4.0.
  • PSA gt 4.0 ng/ml 25 risk of cancer.
  • Screening proliferated.

16
How did that happen?Circa 2004.
PSA Likelihood of biopsy Risk of cancer Published risk of cancer
0-2 Almost none Very low 1
2-4 Rare Low 15
4-10 Many High 25
gt10 Most Very high 50
17
Your PSA is Elevated. You need a biopsy.
PSAgt4.0
Your PSA is Normal. No testing is necessary.
PSAlt4.0
18
Thompson IM et al. N Engl J Med 20043502239-46
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Population Screening with PSATrue Outcomes
4.0
Screen 10,000 Men PSA 4 760 Cancer
190 High grade 36 PSA lt4
9240 Cancer 1386 High grade 208
PSA 4 7.6 Positive biopsy
25 High grade 19
lt4.0
Normal PSA 92.4 Positive biopsy
15 High grade 15
PSA
SEER, PCAW, Prostate Cancer Prevention Trial Data
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Pause just a moment.You ask your doc, whats
the chance I might have heart problems?
  • What does he check to determine your risk?
  • Just cholesterol?

23
Pause just a moment.You ask your doc, whats
the chance I might have heart problems?
  • What does he check to determine your risk?
  • Just cholesterol?
  • Of course not! Hell use
  • Cholesterol, HDL, VDL
  • Do you smoke?
  • Whats your blood pressure?
  • Male or female?
  • Family history of heart disease, etc

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So why should your doc only use PSA?
  • Other factors that affect risk
  • Digital rectal examination
  • Age
  • Race/ethnicity
  • Family history
  • Prior negative biopsy

26
How to find the National Cancer Institutes risk
calculator
  1. Google prostate cancer risk calculator
  2. Click on top hit

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Two examples of why this is important
  • 55 yo WM, -FHx, prostate nodule, no prior biopsy,
    PSA 0.3
  • 68 yo AAM, FHx, normal prostate, no prior
    biopsy, PSA 2.4

36
Two examples of why this is important
  • 55 yo WM, -FHx, DRE, no prior bx, PSA 0.3
  • 68 yo AAM, FHx, DRE-, no prior bx, PSA 2.4
  • Cancer Risks
  • 1st man Cancer13 High grade cancer1
  • 2nd man Cancer31. High grade 11

37
PCA3 A novel urine marker for prostate cancer
Likelihood ratios evaluated on a cohort of 521
U.S. men (not from the PCPT cohort) exceeded 1
for high values of PCA3, i.e. PCA3 provided
independent predictive value to PSA and the other
PCPT risk factors.
Likelihood Ratio
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www.prostate-cancer-risk-calculator.com
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PLCO results
45
PLCO results
46
ERSPC results
Absolute risk reduction of 0.71 PCA death per
1000 men after 8.8 years, a 20 reduction in risk
of cancer death. Based on compliance rate of 82
for screening.
47
Vision of the Future at the CTRC - 2011
  • Man with low future risk of prostate cancer Go
    home, see you in 2021.
  • Man without cancer and elevated PSA No biopsy!
  • Man with low-risk cancer Watch it, carefully.
  • Man with high-risk cancer Perform a biopsy,
    initiate effective treatment, oftentimes several
    treatments combined.
  • Avoid treatment in those who dont need it.
  • For those with life-threatening cancer cure it!

48
Options for Control of Prostate Cancer
  • Cure the disease when it presents
    symptomatically.
  • Screen for the disease treat it when you find
    it.
  • Prevent it.

49
Hormone Action in the prostate
x
50
PCPT Schema
Enrollment
1993-1997
1994-1997
Randomization
Placebo
Finasteride
Follow-up every 3 months. Annual PSA, DRE
End of Study Biopsy
End of Study Biopsy
2001-2003
51
Prostate Cancers
52
To Detect Prostate Cancer
  • two things are necessary
  • You must first suspect cancer.
  • PSA or DRE must be abnormal
  • You must then diagnose cancer.
  • Your needle must strike the tumor.

53
What we have learned about finasteride and cancer
detection
  • Finasteride
  • Improves cancer detection using PSA
  • Improves cancer detection with prostate
    examination
  • Improves cancer detection with prostate biopsy
  • Both cancers and aggressive cancers

54
PSA Sensitivity
  • Screening PSA value that prompts prostate biopsy
  • 4.0 ng/mL on placebo
  • Adjusted value on finasteride

Specificity Sensitivity No Finasteride Sensitivity With Finasteride
Prostate cancer 92.7 24.0 37.8
Gleason 7 cancer 90.5 39.2 53.0
Gleason 8 cancer 89.5 49.1 64.2
  • Thompson, et al., JNCI. 200698.

55
Results adjusted for bias
  • Cancer
  • 30 reduction in risk
  • Gleason 6
  • 32 reduction in risk
  • Gleason 7
  • 28 reduction in risk!

56
Reduction in risk of prostate enlargement complica
tions with finasteride
57
How about other ways to prevent prostate cancer?
  • Considerable evidence suggests that selenium and
    Vitamin E can reduce risk
  • Animal studies, cell studies, population studies
  • Based on this evidence, National Cancer Institute
    sponsored large clinical trial

58
Updated Results from SELECTThe Selenium and
Vitamin E Cancer Prevention TrialSponsored
byThe National Cancer InstituteCoordinated by
SWOG,A National Cancer Institute-Supported
Clinical Trials Cooperative Group
59
SELECT Schema
60
SELECT Study Supplements
  • Selenium
  • 200 µg/d from L-selenomethionine or matched
    placebo
  • Vitamin E
  • 400 IU/d all rac-a-tocopheryl acetate or matched
    placebo

61
DSMC Recommendation Sept. 2008
  • On September 15, 2008, the independent SELECT
    DSMC met and made the recommendation to
    discontinue study supplementation
  • No evidence of benefit for prostate cancer
    incidence
  • Planned reduction in prostate cancer incidence
    extremely unlikely in all arms and would not be
    seen within the timeframe of the trial (plt.0001)

62
Prostate Cancers October 2008
Placebo (n8696) Vitamin E (n8737) Selenium (n8752) Combination (n8703)
Prostate Cancers Prostate Cancers Prostate Cancers Prostate Cancers Prostate Cancers
Total 416 473 432 437
HR (99 CI) 1.00 1.13 (0.95 1.35) 1.04 (0.87 1.24) 1.05 (0.88 1.25)
p - value --- p 0.06 p 0.62 p 0.52
63
Diabetes Diagnoses October 2008
Placebo (n7156) Vitamin E (n7215) Selenium (n7210) Combination (n7248)
Diabetes diagnoses Diabetes diagnoses Diabetes diagnoses Diabetes diagnoses Diabetes diagnoses
Number () 669 (9.3) 700 (9.7) 724 (10.0) 660 (9.1)
Relative Risk (99 CI) 1.00 1.04 (0.91 1.18) 1.07 (0.94 1.22) 0.97 (0.85 1.11)
p-value -- p 0.47 p 0.16 p 0.61
Based on self-report of diabetes or reported use
of diabetes medications of the glitazone
class. Excludes prevalent cases at randomization
(n3625) and participants not evaluated for
diabetes because they either died or were lost to
follow-up prior to the assessment (n2434).
64
Current Status
  • Sites continued to follow participants as the
    study transitioned to Centralized Follow-Up
  • DSMC met via teleconference on May 20, 2011
  • Reviewed final data collected by Study Sites on
    their participants
  • Meeting coincided with original plan for a final
    analysis at 7-years after the last participant
    was randomized
  • Recommended that the updated results for Vitamin
    E vs. placebo be reported
  • Published in JAMA October 12, 2011

65
Prostate Cancers July 2011
Placebo (n8696) Vitamin E (n8737) Selenium (n8752) Combination (n8702)
Prostate Cancers Prostate Cancers Prostate Cancers Prostate Cancers Prostate Cancers
Total (increase) 529 (113) 620 (147) 575 (143) 555 (118)
HR (99 CI) 1.00 1.17 (1.004 1.36) 1.09 (0.93 1.27) 1.05 (0.89 1.22)
p - value --- p 0.008 p 0.18 p 0.46

Absolute risk (cases per 1,000 person years) 9.3 10.9 10.1 9.7
66
Prostate Cancer Stage and Grade
Placebo (n529) Placebo (n529) Vitamin E (n620) Vitamin E (n620) Selenium (n575) Selenium (n575) Combination (n555) Combination (n555)
T-Stage T-Stage T-Stage T-Stage T-Stage T-Stage T-Stage T-Stage T-Stage
T1 a-c 375 72 460 75 425 76 391 72
T2 a-b 143 27 138 23 127 23 144 26
T3 a-b 1 0 3 0 3 1 2 1
Gleason Score Gleason Score Gleason Score Gleason Score Gleason Score Gleason Score Gleason Score Gleason Score Gleason Score
4 - 6 286 69 310 67 281 64 281 63
7 102 24 118 25 135 31 124 28
8-10 31 7 37 8 26 6 40 9
Not graded 110 155 134 110

67
Secondary Endpoints
Placebo (n8696) Vitamin E (n8737) Selenium (n8752) Combination (n8702)
Any cancer (including prostate) 1108 1190 1.07 (0.96 1.19) 1132 1.02 (0.92 1.14) 1149 1.02 (0.92 1.14)
Lung cancer 92 104 1.11 (0.76 1.61) 94 1.02 (0.70 1.50) 104 1.11 (0.76 1.62)
Colorectal cancer 75 85 1.09 (0.72, 1.64) 74 0.96 (0.63 1.46) 93 1.21 (0.81 1.81)
Other primary cancer 579 570 0.97 (0.83 1.14) 557 0.96 (0.83 1.13) 594 1.02 (0.92 1.14)
Deaths 564 571 1.01 (0.86 1.17) 551 0.98 (0.84 -1.14) 542 0.96 (0.82 1.12)
Numbers presented are N, Hazard Ratio (99
Confidence Interval) all p-values gt 0.12
Other than prostate, colorectal or lung
68
Cumulative Incidence of Prostate Cancer
69
Vitamin E versus Placebo and Prostate Cancer
Vitamin E
Placebo
p .008
70
Vitamin E versus Placebo and Prostate Cancer
71
Conclusions
  • Healthy men with average risk of prostate cancer
    using community standards of screening and biopsy
    who took a common dose and formulation of vitamin
    E have a 17 increased risk of prostate cancer
  • Statistically significant interaction between
    vitamin E and selenium
  • Caution should be used when designing, analyzing
    and interpreting trials with multiple agents
  • Consumers should be skeptical of health claims
    for unregulated over-the-counter products in the
    absence of strong evidence from clinical trials

72
Conclusions
  • Finasteride significantly reduces a mans risk of
    prostate cancer
  • Risk reduction of cancer is at least 26
  • Increase in high-grade cancers with finasteride
    is likely due to improved detection
  • A cost-effective approach to prevention
  • Other agents (Se, Vit E, others?) do not appear
    to be effective and could cause harm.

73
Conclusions high grade cancer
  • A man taking finasteride, in the short run, has a
    higher risk of a diagnosis of high grade cancer.
  • Evidence strongly shows that a major part of that
    reason is that finasteride helps detect cancers.
  • A benefit to the medication as many of these
    cancers are missed until it is too late to cure
    the disease
  • There is the potential that the medication may
    cause high grade cancer
  • On balance, the majority of men have a benefit,
    reducing risk of cancer and prostate enlargement

74
National Considerations
  • With 217,000 men diagnosed with prostate cancer
    in the US annually, a 25-30 reduction would have
    a significant public health impact

75
National Considerations Vit E
  • About 50 of men and women over 60 take vitamin
    E. About 25 take this dose.
  • Simply stopping this supplement which has no
    other benefits, will reduce their risk by 17.
  • Tens of thousands of men each year will not be
    diagnosed with cancer as a result.

76
QUESTIONS?
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