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 No. of deaths % of all deaths Rank Cause of Death 1. Heart Diseases 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 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* 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 3% lymphoma Urinary bladder 3% Kidney 3% All other sites 23% 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.

Cerebrovascular Diseases Change in the US Death Rates* by Cause, 1950 & 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

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 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

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

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.

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. 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? 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.

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

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. 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

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 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.

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 12-15 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.

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

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

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.

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

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.

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