Johns Hopkins Hospital
Screening, Prevention, Treatment. Are We Winning the War on Prostate Cancer?
Patrick C. Walsh, M.D.
University Distinguished Service Professor The James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions
Demographics
The present The past The future
Demographics
The present The past The future
A Few Basic Facts Prostate Cancer in the U.S. and Australia/New Zealand Life-time risk:
1 out of 6 in the U.S. - 17%. 1 out of 5 in Australia 20%*
*[Link]
2010
A Few Basic Facts Prostate Cancer in the U.S. and Australia/New Zealand Life-time risk:
1 out of 6 in the U.S. - 16%. 1 out of 5 in Australia 20%
Age adjusted incidence:
Australia/New Zealand 104 (highest in the world) U.S. 85.6 (third highest)*
* GLOBOCAN 2008
GLOBOCAN 2008
Age-adjusted mortality/100,000
GLOBOCAN 2008
Age-adjusted mortality/100,000
19.3
GLOBOCAN 2008
Age-adjusted mortality/100,000
15.7
16.2
19.3
15.4
GLOBOCAN 2008
Age-adjusted mortality/100,000
15.7
9.9
16.2
19.3
15.4
Demographics
The present The past The future
Deaths from Cancer in US Men
Lung
LL
Prostate Colon
Prostate Cancer PSA Testing
Prostate Cancer PSA Testing
Trends in death rates for Prostate cancer (ICD10 C61), Australia, 19682007
Prostate Cancer Death Rate in Australia 1968-2007
Male ASM rate Female ASM rate
50 45 40 Deaths per 100,000 35 30 25 20 15 10 5 0 1965 1970 1975 1980 1985 Year 1990 1995 2000 2005 2010
1993
Cause of Death in Men Cause C Younger Than 85
PSA Testing
Prostate Cancer PSA Testing
Prostate Cancer PSA Testing 50%
Deaths from Cancer in US Men
Lung (71)
LL
( Ave Age at Death)
Prostate (80) Colon (73)
Change in life expectancy 1975 2000 White men 69 76 years Black men 64 - 73 years
Weden, M.M. Rand Corporation 2007
Demographics
The present The past The future up to this point we have been
looking at incidence and mortality rate/100,000 men not the number of cancers or deaths/year
The 80 Million Baby Boomers are Aging
Strategy to Reduce Deaths and Suffering (Metastases)
Primary prevention Secondary prevention early diagnosis and effective treatment
Strategy to Reduce Deaths and Suffering (Metastases)
Primary prevention
Strategy to Reduce Deaths and Suffering (Metastases)
Primary prevention
Chemoprevention Lifestyle changes
Rationale for Chemoprevention of Prostate Cancer
The highest age-specific incidence of any cancer and if it were possible to just delay its onset it would be possible to reduce death and suffering
35,500 men randomized to selenium, Vitamin E 400 IU, the combination, or placebo. Trial abruptly terminated 5 years early when there was no significant effect JAMA 2008
14,600 male physicians randomized to Vitamin E 400 IU, Vitamin C 500 mg, placebo for 10 years. No effect
Chemoprevention
Unfortunately, today there is no pill that will prevent the disease! That includes selenium, Vitamin E, Vitamin D, Vitamin C, zinc.
Chemoprevention
Unfortunately, today there is no pill that will prevent the disease! That includes selenium, Vitamin E, Vitamin D, Vitamin C, zinc. If oxidative damage is involved in the progression of prostate cancer, why don t antioxidants work?
Chemoprevention
Unfortunately, today there is no pill that will prevent the disease! That includes selenium, Vitamin E, Vitamin D, Vitamin C, zinc. If oxidative damage is involved in the progression of prostate cancer, why don t antioxidants work? When a man from Asia moves to the West, his risk of prostate cancer does not increase for 20-25 years. Starting a preventive strategy at age 50 may be too late.
normal prostate epithelium proliferative inflammatory atrophy
exposure to inflammatory oxidants
prostatic intraepithelial neoplasia localized prostate cancer
exposure to dietary oxidants and electrophiles Age 20-30 50
metastatic prostate cancer
Chemoprevention
What about multivitamins? This study, which confirms 2 other studies, shows that men who take more than 1 vitamin pill per day have an increased risk of developing advanced prostate cancer and dying from it!
Lawson KA et al;. JNCI 2007; 99:754
What About Finasteride/Dutasteride The Short Story
The FDA rejected GSK s application for use of dutasteride in prevention of prostate cancer. The FDA warned all physicians against use of these agents for the prevention of prostate cancer because they increase the risk of high grade disease, which the FDA showed was not an artifact caused by prostate shrinkage nor improved performance of PSA. High grade disease is a fact, not an artifact. Worldwide, GSK has withdrawn all applications for the use of Avodart for prevention. Merck s product insert states that Proscar is not indicated for the prevention of prostate cancer.
Strategy to Reduce Deaths and Suffering (Metastases)
Primary prevention
Chemoprevention Lifestyle changes
Lifestyle Changes
Maintain a healthy weight through dietary restriction and exercise. Obesity is the number one cause of aggressive life threatening disease Eat more fruits, vegetables (especially cruciferous), whole grains, fish and avoid red meat, processed meat (deli meats, bacon), charred meat (PhIP), refined sugars Stop smoking!! Smoking at the time of the diagnosis increases the risk of advanced disease and dying from it.
Strategy to Reduce Deaths and Suffering (Metastases)
Primary prevention Secondary prevention early diagnosis and effective treatment
Unequivocal Evidence That PSA is Valuable
In the past, before PSA was available, most men with prostate cancer were diagnosed with incurable disease.
Impact of PSA on Stage at Diagnosis
Year Localized disease 68% Metastases to bone 21%
1990
Unequivocal Evidence That PSA is Valuable
In the past, before PSA was available most men with prostate cancer were diagnosed with incurable disease. With the advent of PSA testing, most men today are diagnosed with curable disease.
Impact of PSA on Stage at Diagnosis
Year Localized disease 68% 91% Metastases to bone 21% 4%
1990 2009
Unequivocal Evidence That PSA is Valuable
In the past, before PSA was available most men with prostate cancer were diagnosed with incurable disease. With the advent of PSA testing, most men today are diagnosed with curable disease. Thus today men have a choice that they never had before: they can undergo testing and if they have cancer can choose treatment or observation, or they can do nothing and run the risk of a diagnosis when it s too late to cure
U.S. Stage-specific Incidence of Prostate Cancer Localized
Metastatic
PSA Testing
Results of Randomized Trials of PSA Testing March 2009 NEJM
European Trial : Result in men who actually underwent PSA screening the reduction in deaths was 27% at 14 years. U.S. Trial: Result: no effect on prostate cancer mortality at 7 years.
ERSPC
PLCO - What Would You Think If You Knew
U.S. trial half the size 76,000 vs 162,000 U.S . trial did not evaluate testing vs no testing 52% of controls had PSA testing!!! It was only more testing vs slightly less.
PLCO - What Would You Think If You Knew
U.S. trial half the size 76,000 vs 162,000 U.S . trial did not evaluate testing vs no testing 52% of controls had PSA testing!!! It was only more testing vs slightly less. Only 30% of the men in the PSA testing arm had a biopsy when their PSA went up!!
PLCO - What Would You Think If You Knew
U.S. trial half the size 76,000 vs 162,000 U.S . trial did not evaluate testing vs no testing 52% of controls had PSA testing!!! It was only more testing vs slightly less. Only 30% of the men in the PSA testing arm had a biopsy when their PSA went up!! No improvement in clinical stage!
Reanalysis of PLCO trial stratifying men for comorbidity In men with no or minimal comorbidity, screening reduced PC deaths by 44% NNT to prevent one prostate cancer death at 10 years was 5!
Radical Prostatectomy Reduces Prostate Cancer Deaths and Improves Overall Survival*
Scandinavian Prostate Group (Sweden, Finland, Iceland) randomized trial of watchful waiting vs. radical prostatectomy. 695 T2 (75%) and T1 mean age 65; median f/u 6 y. Follow-up 12 years following randomization.
Lars Holmberg, et al N Engl J Med 347::781 2002 Bill-Axelson, et al N Engl J Med 352: 1977, 2005 and J Natl Cancer Inst 2008; 100: 1144-1154
Lessons Learned
At 12 years men who underwent surgery had a significant absolute reduction in death from cancer, metastases , and local progression . Effect most dramatic in men < 65 years old.
Results in Men < 65 years at Randomization
Overall Mortality
WW RP WW RP
Prostate Cancer Deaths
= Watchful waiting men < 65 yo
Ratio of Rural/ Urban
Summary Are We Winning the War
Australia/New Zealand and the U.S. share a high incidence and mortality from prostate cancer. With the expansion of the population of aging men this number will increase markedly in the future. Although the application of aggressive screening and effective therapy have achieved a significant reduction in mortality, this has been associated with over diagnosis, over treatment and unnecessary morbidity. We may be on the way to winning the war, but there are many obstacles to overcome before we can declare victory
Obstacles/Challenges
New approaches to prevention. And do we need to start earlier and if so would anyone do it? Improved strategies/markers to avoid over diagnosis. Imaging to provide accurate quantitation of the extent and location of tumor within the prostate. Continued refinement in surgical techniques to reduce morbidity without reducing efficacy. Innovative approaches to advanced disease to provide effective systemic adjuvant treatment for patients with adverse pathology following primary therapy.
50% Relative Risk Reduction in Metastases
These data demonstrate a significant decrease in metastases in men with Gleason