1. CANCER SCREENING LATEST EVIDENCE
Madeleine Makhlouf Akel, MD
American University Of Beirut
Lebanese Society of Family Medicine
5th annual conference
Nov. 11–12, 2006.

2. US Mortality, 2003 No. of deaths % of all deaths Rank Cause of Death
1. Heart Diseases 685,
2. Cancer ,
3. Cerebrovascular diseases 157,
4. Chronic lower respiratory diseases 126,
5. Accidents (Unintentional injuries) 109,
6. Diabetes mellitus 74,
7. Influenza and pneumonia 65,
8. Alzheimer disease 63,
9. Nephritis ,
10. Septicemia ,
Source: US Mortality Public Use Data Tape 2003, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.

3. 2006 Estimated US Cancer Deaths*
Men 291,270
Women 273,560
Lung & bronchus 31%
Colon & rectum 10%
Prostate 9%
Pancreas 6%
Leukemia 4%
Liver & intrahepatic 4% bile duct
Esophagus 4%
Non-Hodgkin % lymphoma
Urinary bladder 3%
Kidney 3%
All other sites %
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% All other sites
ONS=Other nervous system.
Source: American Cancer Society, 2006.

4. Cerebrovascular Diseases
Change in the US Death Rates* by Cause, & 2003
Rate Per 100,000
1950
2003
Pneumonia/ Influenza
Heart Diseases
Cerebrovascular Diseases
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

5. Early Cancer Detection
Application of cancer screening in practice remains deficient despite the available recommendations

6. 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.

7. CANCER SCREENING LATEST EVIDENCE
Breast Cancer
Colorectal Cancer
Prostate Cancer
Lung Cancer

8. BREAST CANCER

9. Breast Cancer Screening Guidelines
American Cancer Society
BSE is an option starting at 20 Y
CBE every 3 years 20 – 40 Y
mammogram every year at age 40 + CBE
High Risk women to discuss with their Doctor:
Earlier screening
More frequent exams
Additional testing
(USPSTF)
BSE or CBE alone Lack evidence for recommendation for or against ( I Rec.)
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

10. At present, BSE cannot be recommended routinely.
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

11. Reduction in breast cancer mortality of 20%
Screening for Breast Cancer with Mammography The Cochrane Database of Systematic Reviews 2006 Issue 4
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.

12. The highest PPVs for mammography were in: Women aged 50 years or older
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 Nov 24;270(20):
JAMA Apr 6;271(13):982-3
Ann Intern Med Dec 5;133(11):855-63 .

13. What are known risk factors for breast cancer?
Age
family history
Age at first pregnancy
Early menarchy
Late menopause
Postmenopausal obesity
Use of postmenopausal hormones
Alcohol consumption
Physical inactivity

14. 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.

15. 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.

16. 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.

17. All observational studies methodological limitations
Women at high Risk for breast Cancer: Bilateral Prophylactic mastectomy The Cochrane Database of Systematic Reviews 2006 Issue 4
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

19. COLORECTAL CANCER

20. 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.
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)
The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer A recommendation.
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.
Patients at an increased risk should begin screening earlier and/or be screened more often

21. 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.

22. 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

23. 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)

24. Colorectal cancer Risk Category Age to Begin Recommend. Comments
INCREASED RISK
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
If normal, repeat examination
in 3 years; If normal then, the
Personal history of
curative-intent resection of
colorectal cancer
Within 1 year
after cancer
resection
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
Every 5-10 years. Colorectal
cancer in relatives more
distant than first-degree does
not increase risk substantially
above the average risk
group.

25. Colorectal cancer Family history of familial adenomatous polyposis
Risk Category
Age to Begin
Recommend.
Comments
HIGH RISK
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
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 years
after the onset of
left-sided colitis
with biopsies
for dysplasia
Every 1-2 years. These patients
experience in the surveillance
and management of inflammatory
bowel disease.

27. PROSTATE CANCER

28. 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

29. 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

30. two randomised controlled trials 55,512 participants were included
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

31. 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 evidence-based decisions regarding prostate cancer screening.

32. 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.

33. 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

34. 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; eliminates PSA elevations due to BPH
Limited data at present on influence of noncancerous conditions 

36. LUNG CANCER

37. 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

38. Lung Cancer Screening Guidelines
USPSTF
American Cancer Society
other US medical organizations
Evidence is not enough to support regular screening for lung cancer

39. 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

40. 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.

41. frequent chest x-ray may cause harm. More research is needed.
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.

42. Thank you