Transcript cancer screening latest evidence

CANCER SCREENING
LATEST EVIDENCE
Madeleine Makhlouf Akel, MD
American University Of Beirut
Lebanese Society of Family Medicine
5th annual conference
Nov. 11–12, 2006.
US Mortality, 2003
1.
Heart Diseases
No. of
% of all
deaths deaths
685,089 28.0
2.
Cancer
556,902
22.7
3.
Cerebrovascular diseases
157,689
6.4
4.
Chronic lower respiratory diseases
126,382
5.2
5.
Accidents (Unintentional injuries)
109,277
4.5
6.
Diabetes mellitus
74,219
3.0
7.
Influenza and pneumonia
65,163
2.7
8.
Alzheimer disease
63,457
2.6
9.
Nephritis
42,453
1.7
10.
Septicemia
34,069
1.4
Rank
Cause of Death
Source: US Mortality Public Use Data Tape 2003, National Center for Health Statistics, Centers for
Disease Control and Prevention, 2006.
2006 Estimated US Cancer Deaths*

Lung & bronchus 31%
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Colon & rectum
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Prostate
9%
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Pancreas
6%
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Leukemia
4%

Liver & intrahepatic 4%
bile duct
10%
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Esophagus
4%

Non-Hodgkin
lymphoma
3%

Urinary bladder
3%

Kidney
3%

All other sites
23%
Men
291,270
Women
273,560
26% Lung & bronchus
15% Breast
10% Colon & rectum
 6% Pancreas
 6% Ovary
 4% Leukemia
 3% Non-Hodgkin
lymphoma
 3% Uterine corpus
 2% Multiple myeloma
 2% Brain/ONS
 23%
ONS=Other nervous system.
Source: American Cancer Society, 2006.
All other sites
Change in the US Death Rates* by Cause,
1950 & 2003
Rate Per 100,000
600
586.8
1950
2003
500
400
300
231.6
193.9
180.7
200
100
53.3
190.1
48.1
21.9
0
Heart
Diseases
Cerebrovascular
Diseases
Pneumonia/
Influenza
Cancer
* Age-adjusted to 2000 US standard population.
Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised.
2003 Mortality Data: US Mortality Public Use Data Tape, 2003, NCHS, Centers for Disease Control and
Prevention, 2006
Early Cancer Detection
Application of cancer screening in
practice remains deficient despite
the available recommendations
Early Cancer Detection
One major barrier to implementation is the
confusion that the physicians express
regarding their knowledge of the
recommendations , more importantly for the
high risk patients.
CANCER SCREENING
LATEST EVIDENCE
 Breast Cancer
 Colorectal Cancer
 Prostate Cancer
 Lung Cancer
BREAST CANCER
Breast Cancer
Screening Guidelines
American Cancer Society
(USPSTF)
 BSE is an option starting at 20 Y
 CBE every 3 years 20 – 40 Y
 BSE or CBE alone Lack
evidence for recommendation
for or against ( I Rec.)
 mammogram every year at age
40 + CBE
 mammogram Every 1-2 years at
age 40 +/- CBE (B Rec.)
 High Risk women to discuss
with their Doctor:
– Earlier screening
– More frequent exams
– Additional testing
 High Risk women to discuss
with their Doctor:
– Earlier screening
– More frequent exams
– Additional testing
Screening for Breast Cancer with Regular BSE or CBE
The Cochrane Database of Systematic Reviews 2006 Issue 4
BSE:
 Two large population-based studies
 388,535 women
 no statistically significant difference in breast cancer
mortality
 Results did not suggest a beneficial effect of screening by
breast self-examination
 There is evidence for harms
At present, BSE cannot be recommended routinely.
CBE:
 no randomized trials of clinical breast examination
Screening for Breast Cancer with Mammography
The Cochrane Database of Systematic Reviews 2006 Issue 4
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seven trials
half a million women.
Reduction in breast cancer mortality of 20%
Screening also lead to overdiagnosis and
overtreatment, with estimated 30% increase
It is thus not clear whether screening does
more good than harm.
Studies looking at positive predictive value of screening
mammography by age and family history
The highest PPVs for mammography were in:
 Women aged 50 years or older
 And women aged 40 years or older with a
family history of breast cancer.
Efforts to promote screening mammography
should focus on women in these groups, in
whom the majority of breast cancers occur and
for whom mammography has the highest
PPVs.
JAMA. 1993 Nov 24;270(20):2444-50
JAMA. 1994 Apr 6;271(13):982-3
Ann Intern Med. 2000 Dec 5;133(11):855-63
.
What are known risk factors for
breast cancer?
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Age
family history
Age at first pregnancy
Early menarchy
Late menopause
Postmenopausal obesity
Use of postmenopausal hormones
Alcohol consumption
Physical inactivity
Women with High Risk for Familial Breast Cancer
Specific family patterns associated with increased risk of
deleterious mutations in the BRCA1 or BRCA2 gene.
(both maternal and paternal family history are important)
 Breast Ca in:
– 2 first degree relatives , one <50 Y at Dx.
– 3 or more first or second degree relatives regardless of
age at Dx.
 Breast + Ovarian Ca: in first and second degree relative.
 Bilateral Breast Ca: in first degree relative
 Breast Ca in a male relative
 Ovarian Ca: in 2 or more first or second degree relatives
regardless of age at Dx.
Women at high Risk for breast Cancer:
genetic testing (USPSTF)
 Family history NOT associated with an
increased risk for deleterious mutations in
breast cancer susceptibility gene 1 (BRCA1)
or gene 2 (BRCA2):
– (USPSTF) recommends against routine referral for
genetic counseling or routine breast cancer
susceptibility gene (BRCA) testing D Recommendation.
– fair evidence regarding important adverse ethical,
legal, and social consequences that could result from
routine referral and testing of these women.
– Interventions such as prophylactic surgery,
chemoprevention, or intensive screening were shown
to cause more harms in this group.
Women at high Risk for breast Cancer:
genetic testing (USPSTF)
 Family history associated with an increased risk for
deleterious mutations in BRCA1 or BRCA2
– (USPSTF) recommends to be referred for genetic counseling and
evaluation for BRCA testing B Recommendation.
 Insufficient evidence regarding important adverse ethical, legal, and
social consequences that could result from referral and testing of
high-risk women.
 Bilateral prophylactic mastectomy BPM is associated with known
harms.
The USPSTF estimated that the magnitude of these potential
harms is small.
The USPSTF concluded that the benefits of referring women with an
increased-risk family history to suitably trained health care providers
outweigh the harms.
Women at high Risk for breast Cancer:
Bilateral Prophylactic mastectomy
The Cochrane Database of Systematic Reviews 2006 Issue 4
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All observational studies
methodological limitations
no randomized trials were found
9 studies assessed psychosocial measures
Results: BPM was effective in reducing both the
incidence of, and death from, breast cancer
Women should be aware of their true risk of
developing breast cancer and the limitations of
current evidence when considering prophylactic
mastectomy
COLORECTAL CANCER
Colorectal Cancer
Screening Guidelines
American Cancer Society
Beginning at age 50, 1 of the 5
options :
 Annual fecal occult blood test (FOBT)
or fecal immunochemical test (FIT)
 A flexible sigmoidoscopy (FSIG) every
5 years
 Annual FOBT or FIT and flexible
sigmoidoscopy every 5 years*
 A double-contrast barium enema every
5 years
 A colonoscopy every 10 years
*Combined testing is preferred over either
annual FOBT or FSIG every 5 years
alone.
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DRE is not recommended as a stand-alone
test for colorectal cancer
Patients at an increased risk should
begin screening earlier and/or be
screened more often
(USPSTF)
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The USPSTF strongly recommends
that clinicians screen men and
women 50 years of age or older for
colorectal cancer A recommendation.
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Same options as ACS guidelines
However:
No direct evidence that screening
colonoscopy or DCBE is effective in
reducing mortality
Newer screening technologies (for
example, computed tomographic
colography) are not found effective
in improving health outcomes.
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Patients at an increased risk should
begin screening earlier and/or be
screened more often
Screening for colorectal cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
 Meta-analysis of mortality results from the randomised controlled trials
 Objective: To determine whether screening for colorectal cancer
reduces colorectal cancer mortality and to consider the benefits and
harms of screening.
 Screening benefits:
– reduction in colorectal cancer mortality
– possible reduction in cancer incidence through detection and
removal of colorectal adenomas
– potentially, treatment of early colorectal cancers may involve less
invasive surgery.
 Harmful effects:
– The physical complications of colonoscopy
– disruption to lifestyle
– stress and discomfort of testing and investigations
– and the anxiety caused by falsely positive screening tests.
Screening for colorectal cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
Conclusion
Although screening benefits are likely to
outweigh harms, more information is needed
about the harmful effects of screening, the
community's responses to screening and
screening costs for different health care
systems
Colorectal Cancer
The conditions indicating higher than average risk
 personal history of colorectal cancer or
adenomatous polyps
 personal history of chronic inflammatory bowel
disease
 strong family history of colorectal cancer or polyps
– cancer or polyps in a first-degree relative [parent,
sibling, or child] younger than 60
– or in 2 first-degree relatives of any age
 known family history of hereditary colorectal
cancer syndromes (familial adenomatous
polyposis or hereditary nonpolyposis colon cancer)
Colorectal cancer
Risk Category
Age to Begin
Recommend.
Comments
People with a single, small
(< 1 cm) adenoma
3-6 years after
the initial
polypectomy
Colonoscopy1
If the exam is normal, the
patient can thereafter be
screened as per average risk
guidelines.
People with a large (1 cm
+) adenoma, multiple
adenomas, or adenomas
with high-grade dysplasia
or villous change.
Within 3 years
after the initial
polypectomy
Colonoscopy1
If normal, repeat examination
in 3 years; If normal then, the
patient can thereafter be
screened as per average risk
guidelines.
Personal history of
curative-intent resection of
colorectal cancer
Within 1 year
after cancer
resection
Colonoscopy1
If normal, repeat examination
in 3 years; If normal then,
repeat examination every 5
years.
Either colorectal cancer or
adenomatous polyps, in
any first-degree relative
before age 60, or in two or
more first-degree relatives
at any age (if not a
hereditary syndrome).
Age 40,
or 10 years
before the
youngest case in
the immediate
family
Colonoscopy1
Every 5-10 years. Colorectal
cancer in relatives more
distant than first-degree does
not increase risk substantially
above the average risk
group.
INCREASED RISK
Colorectal cancer
Risk Category
Age to Begin
Recommend.
Comments
Family history of familial
adenomatous polyposis
(FAP)
Puberty
Early
surveillance by
endoscopy, and
counseling to
consider
genetic testing
If the genetic test is positive,
colectomy is indicated. These
patients are best referred to a
center with experience in the
management of FAP.
Family history of hereditary
non-polyposis colon cancer
(HNPCC)
Age 21
Colonoscopy
and counseling
to consider
genetic testing
If the genetic test is positive or if
the patient has not had genetic
testing, every 1-2 years until age
40, then annually. These patients
are best referred to a center with
experience in the management of
HNPCC.
Inflammatory bowel disease
Chronic ulcerative colitis
Crohn's disease
Cancer risk begins
to be significant 8
years after the
onset of pancolitis,
or 12-15 years
after the onset of
left-sided colitis
Colonoscopy
with biopsies
for dysplasia
Every 1-2 years. These patients
are best referred to a center with
experience in the surveillance
and management of inflammatory
bowel disease.
HIGH RISK
PROSTATE CANCER
Prostate Cancer
Screening Guidelines
American Cancer Society
And other US medical
organizations:
 PSA and DRE
(if life expectancy is at least 10 yrs)
Average risk: Beginning at age 50
High risk: Beginning at age 45
Higher risk: Beginning at age 40
(USPSTF)
 Evidence is insufficient to
recommend for or against
routine screening for prostate
cancer using PSA or DRE:
I recommendation
Prostate Cancer
Conditions indicating higher than average risk
 Men at High risk:
– African Americans
– 1or more family member (father, brother) diagnosed
before age 65
 Men at very high risk:
– Multiple first-degree relatives affected at an
early age
Screening for prostate cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
Objectives:
 To determine whether screening for prostate
cancer reduces prostate cancer mortality and
has an impact on quality of life.
 two randomised controlled trials
 55,512 participants were included
 both trials had methodological weaknesses
with high risk of bias
Screening for prostate cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
Results :
 Insufficient evidence to either support or refute the
routine use of mass, selective or opportunistic
screening compared to no screening for reducing
prostate cancer mortality
 no robust evidence from randomised controlled trials is
available regarding the impact of screening on quality
of life, harms of screening, or its economic value.
 Results from two ongoing large scale multicentre
randomised controlled trials that will be available in the
next several years are required to make evidencebased decisions regarding prostate cancer screening.
Prostate Cancer
Screening Guidelines
For men at average risk and high risk,
information should be provided about what is
known and what is uncertain about the benefits
and limitations of early detection and treatment
of prostate cancer so that they can make an
informed decision about testing.
Prostate Cancer
Screening Guidelines
What if the patient asks the doctor to
make the decision on his behalf?
The ACS recommends that these men
should be tested.
Discouraging testing is not appropriate.
Also not offering testing is not appropriate
Prostate Cancer Screening Tests
Tests to Improve
Specificity PSA*
Advantages
Disadvantages
Age-adjusted PSA Considers that BPH increases
with age and accepts that
detection of disease in older
men is less "valuable" than in
younger men
Significant increase in
biopsies for younger men;
assumes similar PSA range
for different races
PSA velocity
Useful for individuals with
numerous PSA values over
several years; may also detect
cancer in patients whose PSA
is < 4.0 ng/mL
Requires multiple PSA values
performed by the same assay
technique; requires testing
over prolonged intervals
PSA density
Directly limits the effect of
BPH
Inaccurate volume
determinations using standard
TRUS technique; expense
and inconvenience of TRUS
Free PSA
Earlier cancer detection;
Limited data at present on
eliminates PSA elevations due influence of noncancerous
to BPH
conditions
LUNG CANCER
Lung Cancer
 Lung cancer is the most common cause of
cancer related death in the western world.
 It takes about 20 years to develop
 Cigarette smoking is a known cause.
 Most lung cancers are not found until they
are advanced
Lung Cancer
Screening Guidelines
USPSTF
American Cancer Society
other US medical organizations
Evidence is not enough to
support regular screening for
lung cancer
Screening for lung cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
Objectives:
To determine whether screening for lung cancer
using regular sputum examinations or chest
radiography or CT chest reduces lung cancer
mortality.
 Total of 245,610 subjects.
 Seven trials were included (6 randomised controlled
studies and 1 non-randomised controlled trial)
 There were no studies with an unscreened control group.
 Several of the included studies had potential
methodological weaknesses.
 There were no controlled studies of spiral CT
Screening for lung cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
Results:
– frequent screening with chest x-rays was
associated with an 11% relative increase in
mortality from lung cancer compared with less
frequent screening
– A non statistically significant trend was
observed for reduced mortality from lung cancer
when screening with chest x-ray and sputum
cytology was compared with chest x-ray alone
– Chest x-ray, testing sputum cytology or CT scan
do not appear to have much impact on either
treatment or number of deaths from lung
cancer.
Screening for lung cancer
The Cochrane Database of Systematic Reviews 2006 Issue 4
CONCLUSION:
frequent chest x-ray may cause harm.
More research is needed.