CANCER SCREENING CANCER SCREENING LATEST EVIDENCELATEST EVIDENCE

Madeleine Makhlouf Akel, MDMadeleine Makhlouf Akel, MDAmerican University Of Beirut American University Of Beirut

Lebanese Society of Family MedicineLebanese Society of Family Medicine55thth annual conference annual conference

Nov. 11–12, 2006.Nov. 11–12, 2006.

US Mortality, 2003US Mortality, 2003

Source: US Mortality Public Use Data Tape 2003, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.

1.1. Heart DiseasesHeart Diseases 685,089685,089 28.0 28.0

2.2. CancerCancer 556,902556,902 22.7 22.7

3.3. Cerebrovascular diseasesCerebrovascular diseases 157,689157,689 6.4 6.4

4.4. Chronic lower respiratory diseasesChronic lower respiratory diseases 126,382 5.2126,382 5.2

5.5. Accidents (Unintentional injuries)Accidents (Unintentional injuries) 109,277 109,277 4.5 4.5

6.6. Diabetes mellitusDiabetes mellitus 74,219 74,219 3.0 3.0

7.7. Influenza and pneumoniaInfluenza and pneumonia 65,163 65,163 2.7 2.7

8.8. Alzheimer diseaseAlzheimer disease 63,457 63,457 2.6 2.6

9.9. NephritisNephritis 42,453 42,453 1.7 1.7

10.10. SepticemiaSepticemia 34,069 34,069 1.4 1.4

Rank Cause of DeathNo. of deaths

% of all deaths

2006 Estimated US Cancer Deaths*2006 Estimated US Cancer Deaths*

ONS=Other nervous system.Source: American Cancer Society, 2006.

Men291,270

Women273,560

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% All other sites

Lung & bronchus 31%

Colon & rectum 10%

Prostate 9%

Pancreas 6%

Leukemia 4%

Liver & intrahepatic 4%bile duct

Esophagus 4%

Non-Hodgkin 3% lymphoma

Urinary bladder 3%

Kidney 3%

All other sites 23%

Change in the US Death Rates* by Cause, Change in the US Death Rates* by Cause, 1950 & 20031950 & 2003

* 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

21.9

193.9

586.8

48.1

180.7

231.6

190.1

53.3

0

100

200

300

400

500

600

HeartDiseases

CerebrovascularDiseases

Pneumonia/Influenza

Cancer

1950

2003

Rate Per 100,000

Early Cancer Detection Early Cancer Detection

Application of cancer screening in Application of cancer screening in practice remains deficient despite practice remains deficient despite the available recommendationsthe available recommendations

One major barrier to implementation is the One major barrier to implementation is the confusion that the physicians express confusion that the physicians express regarding their knowledge of the regarding their knowledge of the recommendations , more importantly for the recommendations , more importantly for the high risk patients.high risk patients.

Early Cancer Detection Early Cancer Detection

Breast CancerBreast Cancer Colorectal CancerColorectal Cancer Prostate Cancer Prostate Cancer Lung CancerLung Cancer

CANCER SCREENING CANCER SCREENING LATEST EVIDENCELATEST EVIDENCE

BREAST CANCERBREAST CANCER

Breast Cancer Breast Cancer Screening GuidelinesScreening Guidelines

American Cancer SocietyAmerican Cancer Society

BSE is an option starting at 20 YBSE 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)(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

BSEBSE:: Two large population-based studiesTwo large population-based studies 388,535 women 388,535 women no statistically significant difference in breast cancer no statistically significant difference in breast cancer

mortality mortality Results did not suggest a beneficial effect of screening by Results did not suggest a beneficial effect of screening by

breast self-examinationbreast self-examination There is evidence for harmsThere is evidence for harms

At present, BSE cannot be recommended routinely.At present, BSE cannot be recommended routinely.

CBE: CBE: no randomized trials of clinical breast examination no randomized trials of clinical breast examination

Screening for Breast Cancer with Regular BSE or CBEScreening for Breast Cancer with Regular BSE or CBEThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

seven trials seven trials half a million women.half a million women. Reduction in breast cancer mortality of 20%Reduction in breast cancer mortality of 20% Screening also lead to overdiagnosis and Screening also lead to overdiagnosis and

overtreatment, with estimated 30% increaseovertreatment, with estimated 30% increase

It is thus not clear whether screening does It is thus not clear whether screening does more good than harm.more good than harm.

Screening for Breast Cancer with MammographyScreening for Breast Cancer with MammographyThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

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 .

Studies looking at positive predictive value of screening Studies looking at positive predictive value of screening mammography by age and family historymammography by age and family history

What are known risk factors for What are known risk factors for breast cancer?breast cancer?

Age Age family historyfamily history Age at first pregnancyAge at first pregnancy Early menarchy Early menarchy Late menopauseLate menopause Postmenopausal obesityPostmenopausal obesity Use of postmenopausal hormonesUse of postmenopausal hormones Alcohol consumptionAlcohol consumption Physical inactivityPhysical inactivity

Women with High Risk for Familial Breast CancerWomen 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: Breast Ca in: – 2 first degree relatives , one <50 Y at Dx.2 first degree relatives , one <50 Y at Dx.– 3 or more first or second degree relatives regardless of 3 or more first or second degree relatives regardless of

age at Dx.age at Dx. Breast + Ovarian Ca: in first and second degree relative.Breast + Ovarian Ca: in first and second degree relative. Bilateral Breast Ca: in first degree relativeBilateral Breast Ca: in first degree relative Breast Ca in a male relativeBreast Ca in a male relative Ovarian Ca: in 2 or more first or second degree relatives Ovarian Ca: in 2 or more first or second degree relatives

regardless of age at Dx.regardless of age at Dx.

Women at high Risk for breast Cancer:Women at high Risk for breast Cancer:genetic testing (USPSTF)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:Women at high Risk for breast Cancer:genetic testing (USPSTF)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:Women at high Risk for breast Cancer:Bilateral Prophylactic mastectomyBilateral Prophylactic mastectomy

The Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 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

COLORECTAL CANCERCOLORECTAL CANCER

American Cancer SocietyBeginning 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 guidelinesHowever:

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

Colorectal Cancer Colorectal Cancer Screening GuidelinesScreening Guidelines

Screening for colorectal cancerScreening for colorectal cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

Meta-analysis of mortality results from the randomised controlled trials Meta-analysis of mortality results from the randomised controlled trials

Objective: To determine whether screening for colorectal cancer reduces colorectal Objective: To determine whether screening for colorectal cancer reduces colorectal cancer mortality and to consider the benefits and harms of screening.cancer mortality and to consider the benefits and harms of screening.

Screening benefits:Screening benefits: – reduction in colorectal cancer mortality reduction in colorectal cancer mortality – possible reduction in cancer incidence through detection and removal of possible reduction in cancer incidence through detection and removal of

colorectal adenomas colorectal adenomas – potentially, treatment of early colorectal cancers may involve less invasive potentially, treatment of early colorectal cancers may involve less invasive

surgery.surgery. Harmful effects: Harmful effects:

– The physical complications of colonoscopyThe physical complications of colonoscopy– disruption to lifestyledisruption to lifestyle– stress and discomfort of testing and investigationsstress and discomfort of testing and investigations– and the anxiety caused by falsely positive screening tests.and the anxiety caused by falsely positive screening tests.

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

Screening for colorectal cancerScreening for colorectal cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

personal history of colorectal cancer or personal history of colorectal cancer or adenomatous polyps adenomatous polyps

personal history of chronic inflammatory bowel personal history of chronic inflammatory bowel disease disease

strong family history of colorectal cancer or polyps strong family history of colorectal cancer or polyps – cancer or polyps in a first-degree relative [parent, cancer or polyps in a first-degree relative [parent,

sibling, or child] younger than 60sibling, or child] younger than 60– or in 2 first-degree relatives of any ageor in 2 first-degree relatives of any age

known family history of hereditary colorectal known family history of hereditary colorectal cancer syndromes (familial adenomatous cancer syndromes (familial adenomatous polyposis or hereditary nonpolyposis colon cancer) polyposis or hereditary nonpolyposis colon cancer)

Colorectal CancerColorectal CancerThe conditions indicating higher than average riskThe conditions indicating higher than average risk

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 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.

Colorectal cancerColorectal cancer

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 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.

Colorectal cancerColorectal cancer

PROSTATE CANCERPROSTATE CANCER

American Cancer SocietyAnd 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 Prostate Cancer Screening GuidelinesScreening Guidelines

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

Prostate CancerProstate CancerConditions indicating higher than average riskConditions indicating higher than average risk

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 cancerScreening for prostate cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 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.

Screening for prostate cancerScreening for prostate cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

For men at average risk and high risk, For men at average risk and high risk, information should be provided about what is information should be provided about what is known and what is uncertain about the benefits known and what is uncertain about the benefits and limitations of early detection and treatment and limitations of early detection and treatment of prostate cancer so that they can make an of prostate cancer so that they can make an informed decision about testing.informed decision about testing.

Prostate Cancer Prostate Cancer Screening GuidelinesScreening 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 Prostate Cancer Screening GuidelinesScreening Guidelines

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 

Prostate Cancer Screening TestsProstate Cancer Screening Tests

LUNG CANCERLUNG CANCER

Lung cancer is the most common cause of Lung cancer is the most common cause of cancer related death in the western world. cancer related death in the western world.

It takes about 20 years to develop It takes about 20 years to develop Cigarette smoking is a known cause. Cigarette smoking is a known cause. Most lung cancers are not found until they Most lung cancers are not found until they

are advancedare advanced

Lung Cancer Lung Cancer

USPSTF American Cancer Society

other US medical organizations

Evidence is not enough to Evidence is not enough to support regular screening for support regular screening for lung cancer lung cancer

Lung Cancer Lung Cancer Screening GuidelinesScreening Guidelines

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 cancerScreening for lung cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 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 cancerScreening for lung cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4

CONCLUSION: frequent chest x-ray may cause harm.

More research is needed.

Screening for lung cancerScreening for lung cancerThe Cochrane Database of Systematic ReviewsThe Cochrane Database of Systematic Reviews 2006 Issue 4 2006 Issue 4