Download Prostate Cancer

To Screen or Not to Screen:
That is the Question………
New Guidelines for Prostate
Cancer Diagnosis: The Global
perspective
Gabriel P. Haas, MD. FACS
Medical Director,
Astellas Scientific and Medical Affairs
This is not an Astellas sponsored presentation and the opinions
expressed are my own
New Guidelines for Prostate Cancer Diagnosis:
The Global perspective
Preguntas:
Usan PSA por detecion temprano de Pca?
Familiares con recommendaciones de USA para
NO USAR PSA?
Acceptan estos recommendaciones en Portugal?
BREAKING NEWS !!!
USPSTF PANEL RECOMMENDS AGINST
PROSTATE CANCER SCREEING WITH PSA
(MAY 2012)
PIVOT TRIAL PUBLISHED IN NEW ENGLAND
JOURNAL OF MEDICINE (367:203, 2012)
JULY 2012:
“RADICAL PROSTATECTOMY HAS NO
SURVIVAL BENEFIT OVER OBSERVATION”
Estimated New Cancer Cases and Deaths By Sex, United States, 2011
From Siegel, R. et al.
CA Cancer J Clin 2011;0:caac.20121v1
Copyright ©2011 American Cancer Society
INTRODUCTION
Generaliztions about prostate
cancer__clinical issues
PCA is very common
PCA left untreated or treated late can be deadly
Early detection with PSA leads to diagnosis of
PCA at much earlier stage
Early detection with PSA PROBABLY leads to
decreased mortality
EPIDEMIOLOGY
PCA starts in 20’s and 30’s and may take
decades to be clinically detectable
Prevalence of PCA is MUCH HIGHER than
clinical cases
Early detection with PSA DOES lead to
detection of some (many) clinically insignificant
cancers
Characterization of early prostate cancer is
difficult because only diagnosed cancers can be
studied – undiagnosed cancers are UNKNOWN
Lifetime Risk of Developing or Dying From
Prostate Cancer*
Lifetime Risk of
Risk
Risk Ratio
Developing Histologic Prostate
Cancer (Autopsy)
42%
11.7
Developing Clinical Prostate Cancer
16.7%
4.4
Dying from Prostate Cancer
3.6%
1
* For a 50 year old American man.
Modified from Scardino PT Urol Clin N Am 1989 and Human Path 1992
Incidence of Prostate Cancer by World Region
North America 92.39
Australia/New Zealand 46.70
Caribbean 42.35
Western Europe 39.55
Northern Europe 34.70
Southern Africa 31.03
Middle Africa 29.58
Tropical S. America 28.05
Central America 24.77
Western Africa 23.85
Temperate S. America 22.86
Micronesia/Polynesia 21.22
Southern Europe 16.91
Eastern Africa 16.75
Eastern Europe14.06
Japan 8.51
Western Asia 7.11
Melanesia 6.04
S.E. Asia 5.85
Other Eastern Asia 5.37
Northern Africa 5.13
S. Central Asia 4.53
China 1.08
0
20
40
60
80
100
Prostate Cancer, USA
Year
2010
Incidence Prevalence Mortality
217,730
?
32,050
2003
220,900
?
28,900
2001
198,100
?
31,500
1999
179,300
?
37,000
1996
317,000
?
41,400
1994
200,000
?
38,000
1990
106,000
?
30,000
1985
86,000
?
24,000
1976
64,000
?
20,000
PSA Level(ng./ml)
% Prostate Ca
0-0.5
6.6%
0.6-1.0
10.1%
1.1-2.0
17.0%
2.1-3.0
23.9%
3.1-4.0
26.9%
Rise in Incidence After PSA, 1988
Dramatic rise in
incidence as
prevalent cases are
culled (2.5X)
Sustained rise in
incidence as earlier
cancers are
detected (1.5X)
Reduction in Prostate Cancer Mortality After PSA
40% decline in PCA
mortality
45 to 70% of the
observed decrease in
mortality “attributable”
to PSA screening
Jemal A, et al. CA Cancer J Clin 2010; 60:277-300
Etzioni R, et al. Cancer Causes Control 2008;19:175-181
Screening for Prostate Cancer
Does it save lives?
Does it lead to OVERDETECTION?
Does it lead to unnecessary treatment?
AUA Guidelines 2009 (New Guidelines at AUA, May 2013)
 Well informed men aged 40 and over who have a life
expectancy of at least 10 years should be offered PSA
and DRE to establish a base line and follow-up should
be individualized
 The decision as to whether to do a biopsy or not should
not rely only on the PSA reading(s) but should take into
account a range of other factors such as free and total
PSA, PSA velocity and density, age of the patient, family
history, ethnicity/race, other illnesses/diagnoses, general
health and previous biopsy history
American Cancer Society 2012 (2/27/12)
The ACS recommends that men make an informed decision
with their doctor about whether to be tested for prostate
cancer. Starting at age 50 men with more than 10 years of
life expectancy should talk to their doctor about the pros and
cons of testing so they can decide if testing is right for them.
If they are African American or have a father or brother who
had prostate cancer before age 65, men should have this talk
with a doctor starting at age 45.
If men decide to be tested, they should have PSA with/without
DRE
How often they are tested should depend on their PSA level
– If PSA < 2.5 ng/ml, may be tested every 2 years
– If PSA > 2.5 ng/ml, recommend annual testing
Screening: NCCN Guidelines
For men with life expectancy of > 10 years
– Life expectancy is comprised of age and comorbidity
Have a risk/benefit discussion
– “Shared decision-making”
Offer baseline DRE and PSA at age 40
If PSA < 1, recheck in 5 years
– Median PSA for a man in his 40s is about 0.75
If PSA > 1 or patient is African-American or +FH, offer annual
screening
Consider biopsy if PSA > 2.5 or rate of rise is > 0.35 ng/mL
per year
NY Times: Health Section 2012
U.S. Panel Says No to Prostate Screening for Healthy Men
By GARDINER HARRIS
Healthy men should no longer receive a PSA blood test to screen
for prostate cancer because the test does not save lives over all
and often leads to more tests and treatments that needlessly cause
pain, impotence and incontinence in many
US Preventive Services Task Force, May, 2012
US Preventive Services Task Force
critiques Screening for Prostate Cancer
For every 1000 men treated for PCa
– 5 die of complications
– 10-70 experience complications but survive
– 200-300 develop long-term complications
Impotence
Incontinence
Increased Morbidity
– Complications of biopsy (68 events/10,000 biopsies)
– Psychological consequences
– Complications of overtreatment
US Preventive Services Task Force
critiques Screening for Prostate Cancer
Main concern: Too many of the patients who
are diagnosed have clinically insignificant
cancers which do not need treatment and
therefore should not be diagnosed
GRADE ‘D’ Recommendation:
Evidence is AGAINST screening
Harms outweigh benefits
Engl JJ Med
2009
NN Engl
Med360:1310,
360:1310,
2009
NN Engl
Med360:1320,
360: 1320,
2009
Engl JJ Med
2009
Comparison of ERSPC and PLCO studies
Control
Screening
Age
PSA screening interval
PSA indication for biopsy
Compliance for PSA test
PCA detected Control
Screening
Follow-up
PCA death rate ratio
ERSPC (Europe)
PLCO (USA)
89,353
72,890
55-69
4 yr (87% men)
>3-4 ng/ml
82%
4,307 (4.8%)
5,990 (8.2%)
15 yr
0.8
(95% CI, 0.65-0.98)
38,350
38,343
55-74
1 yr (6 yr period)
>4 ng/ml
85%
2,974
3,452
10 yr
1.1
(95% CI, 0.75-1.70)
Randomized US Study
GL Andriole et al. NEJM 360:1310, 2009
Randomized European Study
FH Schroder et al. NEJM 360:13220, 2009
Limitations of the studies
ERSPC (EU)
PSA test prior to the study
PLCO (USA)
?
43%
PSA test compliance
82%
85%
PSA test in controls
?
52%
ERSPC: PROS AND CONS
Absolute risk difference: 0.71 deaths/1000
For each cancer death prevented, 48
cancer cases need to be detected AND
treated – 1410 men need to be screened
OVERDETECTION -- 50% of cancers
detected by screening would not be
detected in the men’s lifetime
ERSPC
ERSPC
162,243 men randomized
Screening q 2-4 years vs. usual care
– PSA > 3 ng/ml
– Sextant biopsies
– Compliance in screening group 82%
– Screening in the control group ?? (20%)
11 years of follow up (median)
Detection was higher in screening group
– 6963 cases vs. 5396, or cumulative incidence of
9.6% vs. 6.0%
At 11 years, 299 prostate-cancer deaths in screening group and 462 in
the control group.
Rate ratio 0.79, 95% confidence interval 0.68-0.91, p=0.003.
ERSPC
Screening  21% reduction in prostatecancer death*
To save 1 life:
Number needed to screen: 1055
Number needed to detect: 37
* Up to 29% reduction if corrected for noncompliance in the screening arm and
contamination of the control arm.
How does prostate cancer
screening efficacy compare with
screening for other common
cancers?
Breast Cancer Screening
(Mammogram)
9 randomized trials with 650,000
participants
Relative risk reduction of 22% at 14 years
Number needed to screen: 1792
S Fletcher. Screening for Breast Cancer. UpToDate.com; accessed January 14, 2010
LL Humphrey. Summary of the Evidence for Breast Cancer Screening. Ann Intern Med 2002;137:344-6
Colon Cancer Screening
5 randomized trials (at least)
Relative risk reduction of 15-21% at 8-13
years
Number needed to screen: 1173
BD Boggs. How does colonoscopy compare with fecal occult blood testing as a screening tool for
colon cancer. JFP 2005; 54(11)
Towler BP, Irwig L, Glasziou P, Weller D, Kewenter J. Screening for colorectal cancer using the
faecal occult blood test, hemoccult. Cochrane Database Syst Rev 2000;(2):CD001216.
Pignone M, Rich M, Teutsch S, Berg AO, Lohr KN. Screening for colorectal cancer in adults at
average risk: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern
Med 2002;137:132–141.
Screening for Prostate Cancer:
Comparison with Other Cancers
Similar risk reduction
Similar number needed to screen
AND
Two recent studies suggest that
appropriately targeted screening may
improve these figures substantially for
prostate cancer…
Goteborg
Planned analysis of one site of the ERSPC
Differs in that
– Randomization occurred before invitation to
participate
– Younger at randomization (median 56 years)
– Lower PSA threshold for biopsy (2.5)
– High compliance with screening (76%) and
follow-through (93%)
– Negligible contamination in the control group
(est. 3%)
– Higher PCa mortality
– Longer follow up (median 14 years)
Hugosson et al, Lancet Oncol 2010
Goteborg
Rate ratio for death from PCa among the
screening group was 0.56 (0.39-0.82, p=0.002)
Number needed to invite to screen 293 and
number needed to treat 12 to prevent one PCa
death.
Hugosson et al, Lancet Oncol 2010
PLCO
Sub-set Analysis of Healthy Men
No Comorbidities
Sub-set analysis of men with
no comorbidities (that
predict cardiovascular or
cancer mortality)
Adjusted hazard ratio for
screening group vs.
unscreened group was 0.56
(0.33-0.95), p=0.03.
Number needed to treat to
prevent one PCa death at
10 years was 5.
Crawford et al, JCO 2011
One or more
Comorbidities
Summary of Randomized Trial
Data
PLCO
– Flawed due to contamination of the control arm
ERSPC
– 21% relative risk reduction
– 1055 needed to screen; 37 needed to treat
Screening is more beneficial
– In younger, healthier men
– As follow up lengthens
– Targeted screening reduces NNS to ~300 and NNT to 10
or 12.
Efforts to Improve Test Characteristics of
PSA
Age-adjusted PSA
PSA velocity : 0.75 ng/ml or 0.35 ng/ml
PSA density : 0.15
PSA doubling time : less clear in pre-tx evaluation
Free PSA : < 18%
OTHER MARKERS?
Improved biopsy regiments
Improved Radiologic Guidance and Identification of
Significant Cancers (MRI fusion, etc)
Decision Tree of Prostate Cancer
Screening, Diagnosis and Treatment
PSA
+/DRE
Decision Tree of Prostate Cancer
Screening, Diagnosis and Treatment
PSA
+/DRE
Prostate
Biopsy
(type of biopsy)
Decision Tree of Prostate Cancer
Screening, Diagnosis and Treatment
PSA
+/DRE
Prostate
Biopsy
(type of biopsy)
Re-Biopsy?
Decision Tree of Prostate Cancer
Screening, Diagnosis and Treatment
Treatment
PSA
+/DRE
Prostate
Biopsy
Re-Biopsy?
Active
Surveillance
(type of biopsy)
Surgery
Radiation
Other
• HIFU
• Focal therapy
• Hormones
Screening Summary
There are potential benefits
– Reduction in morbidity due to progressive disease
– 20-40% prostate-cancer specific survival benefit
– More likely to benefit younger, healthier patients
There are potential harms
– False-positive test leading to other tests
– Detection of indolent prostate cancer leading to
unnecessary treatment
Screening decisions must
– Balance potential benefits and potential harms
– Involve the patient – “shared decision-making”
Leads us to…
LATIN AMERICA….
AFRICA….
ASIA…..
The issues are different:
–
–
–
–
–
PSA use very limited
Prostate cancer presents in advanced form
Mortality from prostate cancer is 50-80%
Effective treatment is unavailable
RESOURCES, RESOURCES ,RESOURCES
Age-standardized rate (world) of PCA
GLOBOCAN 2008
Incidence Mortality
Ratio
(per 100,000)
(incid./mortality)
World
USA
Canada
Congo
Kenya
Senegal
Tanzania
Uganda
Portugal
25.3
124.8
78.2
29.0
16.6
7.5
20.1
38.0
50.1
8.2
15.8
16.6
25.2
14.1
6.5
17.4
32.5
15.2
3.09
7.90
4.71
1.15
1.18
1.15
1.56
1.17
3.36
CONCLUSIONS
Prostate Cancer Screening
Prostate cancer mortality is dropping in
Western Countries
Trials to PROVE that screening saves lives
are very expensive
Methodologies and follow up different
Very little difference may be detected in
societies where PSA use has been pervasive
However, in Portugal, recommendations
from US may not be applicable