Translational Cancer Research
From Laboratory to Practice
William J Catalona MD
Professor of Urology
Director, Clinical Prostate Cancer Program
Northwestern University
Chicago, Illinois
Cancer in Perspective
In the US and Globally
US Mortality, 2006
Rank Cause of Death
No. of % of all
deaths deaths
•
•
•
1.
Heart Diseases
631,636
26.0
2.
Cancer
559,888
23.1
•
•
•
•
•
•
•
•
•
•
•
3.
Cerebrovascular diseases
137,119
5.7
4.
Chronic lower respiratory diseases
124,583
5.1
5.
Accidents (unintentional injuries)
121,599
5.0
6.
Diabetes mellitus
72,449
3.0
7.
Alzheimer disease
72,432
3.0
8.
Influenza & pneumonia
56,326
2.3
•
9.
Nephritis*
45,344
1.9
•
10. Septicemia
34,234
1.4
*Includes nephrotic syndrome and nephrosis.
Source: US Mortality Data 2006, National Center for Health Statistics, Centers for Disease Control and Prevention,
2009.
2009 Estimated US Cancer Cases*
Men
766,130
Women
713,220
Prostate
25%
27%
Breast
Lung & bronchus
15%
14%
Lung & bronchus
Colon & rectum
10%
10%
Colon & rectum
Urinary bladder
7%
6%
Uterine corpus
Melanoma of skin
5%
4%
Non-Hodgkin
lymphoma
5%
Non-Hodgkin
lymphoma
4%
Melanoma of skin
Kidney & renal pelvis
5%
4%
Thyroid
Leukemia
3%
3%
Kidney & renal pelvis
Oral cavity
3%
3%
Ovary
Pancreas
3%
3%
Pancreas
19%
22%
All Other Sites
All Other Sites
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2009.
Lifetime Probability of Developing Cancer, Men, 2003-2005*
Site
Risk
All sites†
Prostate
1 in 2
1 in 6
Lung and bronchus
1 in 13
Colon and rectum
1 in 18
Urinary bladder‡
1 in 27
Melanoma§
1 in 39
Non-Hodgkin lymphoma
1 in 45
Kidney
1 in 57
Leukemia
1 in 67
Oral Cavity
1 in 72
Stomach
1 in 90
* For those free of cancer at beginning of age interval.
† All Sites exclude basal and squamous cell skin cancers and in situ cancers except urinary bladder.
‡ Includes invasive and in situ cancer cases
§ Statistic for white men.
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.3.0 Statistical Research and
Applications Branch, NCI, 2008. http://srab.cancer.gov/devcan
Lifetime Probability of Developing Cancer, Women, US, 2003-2005*
Site
Risk
All sites†
Breast
1 in 3
1 in 8
Lung & bronchus
1 in 16
Colon & rectum
1 in 20
Uterine corpus
1 in 40
Non-Hodgkin lymphoma
1 in 53
Urinary bladder‡
1 in 84
Melanoma§
1 in 58
Ovary
1 in 72
Pancreas
1 in 75
Uterine cervix
1 in 145
* For those free of cancer at beginning of age interval.
† All Sites exclude basal and squamous cell skin cancers and in situ cancers except urinary bladder.
‡ Includes invasive and in situ cancer cases
§ Statistic for white women.
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.3.0 Statistical Research and
Applications Branch, NCI, 2008. http://srab.cancer.gov/devcan
Cancer Incidence Rates* Among Men, US, 1975-2005
PSA Era
Rate Per 100,000
250
Prostate
200
150
Lung & bronchus
100
Colon and rectum
50
Urinary bladder
Non-Hodgkin lymphoma
Melanoma of the skin
0
1975
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005
Cancer Incidence Rates* Among Women, US, 1975-2005
Rate Per 100,000
250
200
150
Breast
100
Colon and rectum
Lung & bronchus
50
Uterine Corpus
Ovary
0
1975
Non-Hodgkin lymphoma
1978
1981
1984
1987
1990
1993
1996
1999
2002
*Age-adjusted to the 2000 US standard population and adjusted for delays in reporting.
Source: Surveillance, Epidemiology, and End Results Program, Delay-adjusted Incidence database:
SEER Incidence Delay-adjusted Rates, 9 Registries, 1975-2005, National Cancer Institute, 2008.
2005
2009 Estimated US Cancer Deaths*
Men
292,540
Women
269,800
30%
26%
Lung & bronchus
Prostate
9%
15%
Breast
Colon & rectum
9%
9%
Colon & rectum
Pancreas
6%
6%
Pancreas
Leukemia
4%
5%
Ovary
Liver & intrahepatic
bile duct
4%
4%
Non-Hodgkin
lymphoma
Esophagus
4%
3%
Leukemia
Urinary bladder
3%
3%
Uterine corpus
Non-Hodgkin
lymphoma
3%
2%
Liver & intrahepatic
bile duct
Kidney & renal pelvis
3%
2%
Brain/ONS
25%
25%
Lung & bronchus
All other sites
ONS=Other nervous system.
Source: American Cancer Society, 2009.
All other sites
Cancer Death Rates* Among Men, US,1930-2005
100
Rate Per 100,000
Lung & bronchus
80
60
PSA Era
Stomach
Prostate
40
Colon & rectum
20
Pancreas
*Age-adjusted to the 2000 US standard population.
Source: US Mortality Data 1960-2005, US Mortality Volumes 1930-1959,
National Center for Health Statistics, Centers for Disease Control and Prevention, 2008.
2005
2000
1995
1990
1985
1980
1975
1970
1965
1960
1955
Liver
1950
1945
1940
1935
0
1930
Leukemia
Cancer Death Rates* Among Women, US,1930-2005
100
Rate Per 100,000
80
60
Lung & bronchus
40
Uterus
Breast
Colon & rectum
Stomach
20
Ovary
*Age-adjusted to the 2000 US standard population.
Source: US Mortality Data 1960-2005, US Mortality Volumes 1930-1959,
National Center for Health Statistics, Centers for Disease Control and Prevention, 2008.
2005
2000
1995
1990
1985
1980
1975
1970
1965
1960
1955
1950
1945
1940
1935
Pancreas
1930
0
Trends in the Number of Cancer Deaths Among Men and Women, US,
1930-2006
300,000
295,000
290,000
Men
285,000
250,000
280,000
Women
275,000
200,000
270,000
Women
265,000
150,000
20
00
20
01
20
02
20
03
20
04
20
05
20
06
Number of Cancer Deaths
Men
100,000
50,000
0
1930
1940
1950
1960
1970
1980
1990
2000
Source: US Mortality Data, 1930-2006, National Center for Health Statistics, Centers for Disease
Control and Prevention, 2009.
Stage of Cancer at the Time of Detection and 5-Year Survival Rates by Stage
Stage at Diagnosis
5-Year Survival for Stage
Does PSA Screening Save Lives?
•
•
•
•
Flawed “PLCO study” from the U.S. study: No
Better “ERSPC study” from Europe: Yes,
by at least 20%
Best “Goteborg study” with longer follow-up,
by 44% to 56%
Recent* Prostate-Specific Antigen (PSA) Test Prevalence (%), by
Educational Attainment and Health Insurance Status, Men 50 Years
and Older, US, 2001-2006
70
Prevalence (%)
60
58
55
2001
2004
52
50
2002
2006
54
46
42
40
39
40
30
30
28
25
27
20
10
0
Total
Less than a high school
education
No health insurance
*A prostate-specific antigen (PSA) test within the past year. Note: Data from participating states and the District of
Columbia were aggregated to represent the United States.
Source: Behavioral Risk Factor Surveillance System Public Use Data Tape (2001, 2002, 2004, 2006), National Center
for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 2002, 2003, 2005,
2007.
What are the latest
guidelines for PSA testing?
2009 NCCN Guidelines for PCa
Detection
• National Comprehensive Cancer Network (NCCN)
• “PSA testing is effective and needs to be more
rigorously conducted in high-risk men”
• “… at age 40, high-risk men be offered a baseline
PSA and prostate exam and if their PSA is 1.0 or
greater, they should have annual follow-up
testing
• Consider prostate biopsy for PSA is higher than
2.5 or increasing by more than 0.35 per year
2010 NCCN Guidelines
• “Screening in men over 75 years should be
considered individually”
• “It is neither the intent nor the suggestion of
the panel that all men diagnosed with
prostate cancer require treatment”
2009 NCCN PCa Management
Guidelines
• A significant change incorporated into the updated NCCN
Guidelines for PCa is the recommendation for active surveillance for
many men
• “Very low risk” category added using a modified Epstein criteria.
Only AS offered and recommended in this category when life
expectancy is < 20 years
• Men with “low-risk’ prostate cancer who have a life expectancy of
less than 10 years should be offered and recommended active
surveillance
• “Together, you and your doctor can carefully weigh several factors
to determine whether active surveillance—that is, not treating the
cancer, but instead watching for any indication that the cancer is
growing—might be the best course of action”
What about active surveillance or
watchful waiting?
Toronto active surveillance update
• UNPROVEN HYPOTHESIS: active surveillance may
reduce overtreatment while retaining option for
curative treatment if the cancer is progressing
• 47% whose cancer was found to be progressing
were free of tumor recurrence after 5 yrs
• Less than 50% had cancer that was still contained
in the prostate at the time of surgery
• In Swedish watchful waiting series with 20 years
of follow-up, almost 50% died of prostate cancer
Johns Hopkins: RRP in Patients Failing
Active Surveillance
• 48 patients who failed active surveillance and
were treated with surgery
• 35% had extension of cancer outside the
prostate gland, 15% had cancer at the surgical
margins, 6% had seminal vesicle/lymph node
involvement
Does prostate cancer run in families?
Prostate Cancer Risk Allele Discovery: Collaboration
of William Catalona with deCODE genetics, Inc.
Locus
SNP
OR
Chicago
OR
All Combined
8q24
rs1447295
1.50
1.53
Amundadottir et al. Nature Genetics 2006
Gudmundsson et al. Nature Genetics 2007a
8q24
rs16901979
2.32
1.66
Gudmundsson et al. Nature Genetics 2007a
17q12
rs4430796
1.41
1.22
Gudmundsson et al. Nature Genetics 2007b
17q24
rs1859962
1.25
1.20
Gudmundsson et al. Nature Genetics 2007b
2p15
rs721048
1.22
1.15
Gudmundsson et al. Nature Genetics2008
Xp11.22
rs5945572
1.23
1.23
Gudmundsson et al. Nature Genetics 2008
5p15
rs401681
1.06
1.07
Rafnar et al. Nature Genetics 2008
5p15
rs2736098
1.20
1.13
Rafnar et al. Nature Genetics 2008
3q21
s10934853
1.21
1.12
Gudmundsson et al. Nature Genetics 2009
8q24
rs16902094
1.16
1.21
Gudmundsson et al. Nature Genetics 2009
19q13
rs8102476
1.15
1.12
Gudmundsson et al. Nature Genetics 2009
11q13 refinement SNP
rs11228565
1.16
1.23
Gudmundsson et al. Nature Genetics 2009
Reference
Might prostate cancer patients carry genetic variants
that predispose to other types of cancer?
Do genetic factors determine prostate
cancer aggressiveness?
Identification of factors associated with risk
for aggressive PCa is urgently needed
Prostate SPOREs Genetics Working
Group
Specialized Program Of Research Excellence
• William Catalona co-chair
• Janet Stanford co-chair
Northwestern
Fred Hutchinson CC
•
•
•
•
•
•
•
Mayo Clinic
Memorial Sloan-Kettering
UCSF
Harvard
Michigan
Baylor
Johns Hopkins
Robert Jenkins
Robert Klein
John Witte
Matt Freedman
Kathy Cooney
Michael Ittmann
William B. Isaacs
• Alternates
• Ken Offit
• Phil Febbo
Memorial Sloan-Kettering
U Calif San Francisco
What else is in the pipeline?
A new “nanotechnology” PSA blood test that is
300 times more sensitive than currentlyavailable tests
Pro-PSA (p2PSA) Multicenter Pivotal Trial
(Beckman-Coulter Incorporated)
Pro-PSA is more accurate than PSA for detecting prostate cancer and aggressive forms of
the disease
William J. Catalona, MD, Lead Investigator.
Sites: Baylor, Erasmus, Harvard, Johns Hopkins, Mayo, Michigan, Northwestern, UCLA
All subject enrollment and sample testing has been completed.
The database is locked and all analyses are complete.
All monitoring has been completed.
BCI audits at 5 sites are complete.
Close-out visits have been completed at 3 sites and all remaining close-out
visits have been scheduled for this year.
EU approval was received July 2009 and product is available in the EU as of 10/16/09.
FDA submission
Review of the clinical section of the FDA submission is complete and has been
forwarded to the BCI regulatory department for final review.
The primary and secondary hypotheses were verified. Results look good.
FDA submission for approval in November 2009.