Cancer Screening and Immunizations in Adults

Cancer Screening and Immunizations in Adults Michael Adams, M.D., FACP Program Director Associate Professor of Medicine Georgetown University Medical Center

Outline • Definitions • Adult Cancer Screening Guidelines • What’s new in cancer screening • Immunizations

Definitions Screening: • testing for disease in average (or low) risk, asymptomatic population • may be considered a form of primary prevention • goals: • early detection • treating to reduce morbidity or mortality • no diagnostic intent • average prevalence (by definition)

Definitions Case-finding: • testing in patients at higher risk • patients seeking medical care because of a complaint • patients with familial risks / exposures / other diagnosis • may be a form of secondary prevention • disease present, reduce mortality / recurrence rate • diagnostic intent • usually higher than average disease prevalence

Operating characteristics • high sensitivity • low burden • early detection • ability to modify course of disease • higher prevalence = better positive predictive value

GUIDELINES • ACP, USPSTF, CTF, NCI, NIH, AMA, ACC, AHA, AUA, ACOG, IOM • USPSTF • evidence-based • frequent updates • factor in net benefit, quality of the evidence

US Preventive Services Task Force (USPSTF) • http://www.ahcpr.gov/clinic/uspstfix.htm

Bladder Cancer • Breast Cancer / BRCA mutations • Cervical Cancer • Colorectal Cancer • Gynecologic Cancers • Lung Cancer • Oral Cancer • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Skin Cancer • Testicular Cancer • Thyroid Cancer • Tobacco Use • Vitamin Supplementation to Prevent Cancer and CHD

USPSTF Ratings • Strength of Recommendations • The U.S. Preventive Services Task Force (USPSTF) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). • Quality of Evidence • The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor).

USPSTF Ratings (Strength) • Recommendation: A - routinely provide to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. • Recommendation: B - routinely provide to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

USPSTF Ratings (Strength) • Recommendation: C - no recommendation for or against routine provision of [the service] At least fair evidence that [the service] can improve health outcomes but concludes that the balance of the benefits and harms is too close to justify a general recommendation. • Recommendation: D - recommends against routinely providing [the service] to asymptomatic patients The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

USPSTF Ratings (Strength) • Recommendation: I - evidence is insufficient to recommend for or against Evidence that [the service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.

USPSTF Ratings (Quality) • Good: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes. • Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes. • Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

D • Bladder Cancer • BRCA mutation • Breast Cancer • Cervical Cancer • Colorectal Cancer • Lung Cancer • Oral Cancer • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Skin Cancer • Testicular Cancer • Thyroid Cancer • Tobacco Use • Vitamin Supplementation to Prevent Cancer and CHD I I D D I D I I/D

Breast Cancer • North America: leading cancer in women, 2nd leading cause of cancer death • 2001: 192,000 diagnoses, 40,200 deaths • >50%: no known major predictors • Risk increases with age, atypical hyperplasia • BRCA-1 and -2 BRCA-1 BRCA-2 breast breast ovary ovary colon colon? prostate prostate? male breast? male breast pancreatic?

Breast Cancer: mammography • Sensitivity 56-95% • Lower in younger, dense breasts, HRT • Specificity 94-97% • More false positives (less specific) in younger women • Abnormal mammogram & chance of cancer: • 40-49: 2-4% PPV • 50-59: 5-9% • 60+: 7-19%

Breast Cancer: Clinical Breast Exam • Sensitivity 40-69% • Specificity 86-99% • 4% of patients with abnormal CBE diagnosed with cancer in a large community trial • These trials compared CBE with mammography, mortality trials use both CBE & mammogram

Breast Cancer: age considerations • Most screening trials 50-69 • 40-49: weaker evidence, delay in benefit (lower prevalence in younger women) • Interval for screening is unknown • Over 70: • evidence generalized unless comorbid conditions reduce life expectancy • Higher absolute risk of cancer • Mammography benefits (absolute) increase with age • Mammography risks (RELATIVE) diminish with age

Breast Cancer • The (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older. B recommendation

Breast Cancer: CBE • The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer. I recommendation

Breast Cancer: Self Breast Exam • Sensitivity 26-41% • Specificity unknown • No known mortality difference • Risks of abnormal self exam • Anxiety • False positive results • Unnecessary biopsies

Breast Cancer: self-exam • The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination (BSE). I recommendation

Breast Cancer: other considerations • Patient preferences, clinical judgment • Family history • BRCA • Other organizations have varying recommendations: • Yearly after age 40: AMA, ACOG, ACS, ACR • Yearly after 50: CTF, AAFP, ACPM • Interval varies (q1, q2 between 40-49) • BSE: ACOG, ACS, AMA, AAFP favor teaching

Chemoprophylaxis for Breast Cancer • tamoxifen and raloxifene may prevent some breast cancers in women at low or average risk for breast cancer • tamoxifen can significantly reduce the risk for invasive ER-positive breast cancer in women at high risk for breast cancer and that the likelihood of benefit increases as the risk for breast cancer increases • raloxifene – consistent evidence (fewer studies)

Chemoprophylaxis – side effects • VTE • Symptomatic side effects (hot flashes) • Endometrial cancer (tamoxifen only) • Need to balance harms vs benefits

Variable Age 45 Age 55 Age 65 Age 75 5-year risk of breast cancer, % No Family history 0.7 1.1 1.5 1.6 Family history 1.6 2.3 3.2 3.4 Benefits per 1,000 women of 5 y of tamoxifen Cases of invasive breast cancer avoided, n No Family history 3-4 5-6 7-8 8 Family history 8 11-12 16 17 Cases of noninvasive breast cancer avoided, n No Family history 1-2 2 2-3 2-3 Family history 2-3 3-4 4-5 5-6 Hip fractures avoided, n <1 3 5 15 Harms per 1000 women of 5 y of tamoxifen Cases of endometrial cancer caused, n 1-2 12 21 "22" Strokes caused, n 1 3 9 20 Pulmonary emboli caused, n 1-2 4-5 9 18 Cases of DVT caused, n 1-2 1-2 3 4 Based upon Gail model

Chemoprophylaxis for Breast Cancer • The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer. D recommendation

Chemoprophylaxis for Breast Cancer • The USPSTF recommends that clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention. Clinicians should inform patients of the potential benefits and harms of chemoprevention. B recommendation

Cervical Cancer • 13,000 cases yearly • 4,100 deaths (2002) • Risks: • early intercourse • increased # of sexual partners • smoking • HPV (95-100% of squamous cell CA of cervix)

Cervical Cancer • Natural history of HPV – slow transition to cancer • “orderly fashion from less severe to more severe dysplasia” • Not faster in HIV+ women (prevalence higher) • Every 6-12 months • Younger women: HPV may be transient • Older women: higher chance of progression to cancer • PAP smear: 60-80% sensitive • New technologies (“ThinPrep”): no good data yet

Cervical Cancer - timing • Interval: every 3 years after 2-3 normals • Sensitivity 60-80% for high grade lesions for a single PAP test • ACS: wait until age 30 to extend screening interval • Annual screening: cervical neoplasia, HPV, other STDs, high risk sexual behavior • Cessation of screening • Low predictive value for women over 65 (ACS: 70), no abnormal PAP in past 10 years • Hysterectomy for benign disease (only cancer in 1995 study of 10,000 PAP smears was vaginal squamous cell CA)

Cervical Cancer – HPV testing • Sensitivity 82% • Specificity 78% • Benefits untested • 8 ongoing studies

Cervical Cancer • The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix. A recommendation

Cervical Cancer • The USPSTF recommends against routinely screening women older than age 65 for cervical cancer if they have had adequate recent screening with normal Pap smears and are not otherwise at high risk for cervical cancer. D recommendation

Cervical Cancer • The USPSTF recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease. D recommendation

The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of human papillomavirus (HPV) testing as a primary screening test for cervical cancer. The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. Cervical Cancer I recommendation I recommendation

ASC-H = atypical squamous cells suspicious for HSIL

Colorectal Cancer • 4th most common cancer in US • 2nd leading cause of cancer death • At age 50, 5% risk of being diagnosed with colon cancer • Adenomatous polyps – precursor • Hereditary polyposis syndromes (FAP, HNPCC) – 6% of all colon cancers

Colorectal Cancer - DRE • Little evidence • Sensitivity much less than multiple test cards • False negatives – no stool in vault • False positives – rectal trauma • Therefore, not recommended as a tool for colorectal cancer screening

Colorectal Cancer - FOBT • sensitivity 26 - 92%, specificity 90-99% • 3 samples, rehydrated cards improve sensitivity (diminishes specificity) • Annual screening has detected 49% of incident cancers • FOBT: 33% reduction in mortality over controls • inexpensive

Colorectal Cancer - sigmoidoscopy • Alone: • detects approximately 7 cancers and 60 large polyps/1000 exams • estimated detection of significant colonic lesions of 80% • Sigmoid abnormalities often trigger colonoscopy • Combination with FOBT: • detects 65-75% of polyps and 40-65% of cancers • reduces mortality by 60% • detects an additional 7 cancers over FOBT alone

Colorectal Cancer - DCBE • Limited studies: sensitivity 86-90% for cancer / polyps • Only 48% sensitive for polyps > 1cm in National Polyp Study • Specificity 85% • No outcome data

Colorectal Cancer - colonoscopy • Sensitivity 90% for large polyps, 75% for small polyps • Specificity difficult to define • Minority of patients who have polypectomy would have developed cancer • PROS: view entire colon, ability to biopsy/treat during procedure • CONS: cost, complications, prep/discomfort

Colorectal Cancer - colonoscopy • The effectiveness of colonoscopy to prevent colorectal cancer or mortality has not been tested in a randomized clinical trial.1 • Comparisons with historical controls: estimates 76-90% reduction in cancers. 1USPSTF website: http://www.ahcpr.gov/clinic/3rduspstf/colorectal/colorr.htm

Colorectal Cancer - costs • Costs for screening, 2002 • Stool hemoccult $7-10 • Flexible sigmoidoscopy $176-299 • Colonoscopy $670-981 excluding facility fee Among 6 high-quality cost-effectiveness analyses examining only direct costs, the average cost-effectiveness ratio values for screening adults older than 50 with each of the major strategies were under $30,000 per life-year saved (Year 2000 dollars). Studies varied as to which strategy was most cost-effective, however. (USPSTF)

Colorectal Cancer • The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer. A recommendation

Colorectal Cancer • Other considerations: • Family history of colon cancer <60: test earlier • “The choice of screening strategy should be based on patient preferences, medical contraindications, patient adherence, and resources for testing and followup.” (USPSTF) • Timing (American Cancer Society) • FOBT: yearly • Sigmoid: every 5 years • DCBE: every 5 years • Colonoscopy: every 10 years • (One-in-a-lifetime after age 55)

Cancer Screening and Immunizations in Adults