E N D
1. Cancer screening Bindu Shah
Senior Talk 2008
2. Case A 52 y.o woman presents to her primary care physicians office for a routine visit. She has not been seen in 4 years and has no significant past medical history. She has no complaints at this time but would like to know if there are any tests she needs.
What would you recommend at this time?
3. Objectives After attending this lecture, participants will be able to
Define a screening test and its uses/pitfalls in ambulatory practice
Describe the United States Preventive Services Task Force and interpret its levels ofrecommendations
Discuss the current USPSTF recommendations regarding 5 common cancer screenings
Discuss the cost-effectiveness data of common cancer screenings and their ultimate impact on cancer prevention
Describe alternative recommendations by various agencies
4. What is the USPSTF? United States Preventive Services Task Force
An independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services. Sponsored since 1998 by the Agency for Healthcare Research and Quality (AHRQ)
5. USPSTF
6. Screening tests A test for a particular disease given to patients who have no symptoms
Should be an important, morbid health condition
Generally cheap
Highly sensitive
Not too demanding or risky
There should be a treatment Sensitive: identify almost all of the people who have the condition tested for)
Sensitive: identify almost all of the people who have the condition tested for)
7. Screening tests Universal screening
Screening all individuals of a certain category (e.g. PKU screening in kids)
Case finding
Screening a small group of individuals based on the presence of risk factors (e.g cancer clusters, family members diagnosed with hereditary disease)
8. Screening tests Adverse effects
Stress and anxiety caused by false positive results
Unnecessary radiation/chemical exposure and test discomfort
Prolonged knowledge of a disease with no treatment
False sense of security over false negative results
Overuse of medical resources
Unnecessary secondary investigations for false positives
Unnecessary secondary investigations for false positives
9. Screening tests Biases
Lead time bias
Length time bias
Selection bias
Overdiagnosis bias
Avoid bias by using Randomized Control Trials (RCTs)
Lead time bias: Diagnosing the disease earlier however having the same mortality as without screening
Length time bias: Slow growing tumors have the better prognoses than fast growing tumors, and screening tests more likely to detect these tumors that are more treatable anyway
Selection bias: -If patients with higher risk of disease are more likely to be screened, screening test results will look worse than they are
Overdiagnosis bias: Test may diagnose abnormalities that would never cause a problem in a persons lifetime (i.e. prostate cancer)
Lead time bias: Diagnosing the disease earlier however having the same mortality as without screening
Length time bias: Slow growing tumors have the better prognoses than fast growing tumors, and screening tests more likely to detect these tumors that are more treatable anyway
Selection bias: -If patients with higher risk of disease are more likely to be screened, screening test results will look worse than they are
Overdiagnosis bias: Test may diagnose abnormalities that would never cause a problem in a persons lifetime (i.e. prostate cancer)
10. Commonly screened diagnoses Cancer (Breast, lung, colorectal, prostate, pancreatic, cervical, ovarian, skin, testicular, thyroid)
Cardiovascular (AAA, Blood pressure, Lipid disorders, carotid artery stenosis, PAD)
Infectious disease (HIV, Hep B/C, STDs, Tuberculosis)
Injury and violence (domestic violence, Youth violence/gang activity, seatbelt use)
Mental health/substance abuse (Etoh, illicit drugs, tobacco, depression, suicide risk)
Endocrine/Metabolism (Diabetes, IDA, obesity, physical activity)
MSK osteoporosis
OB/Gyn (Pre-eclampsia, Rh incompatibility, neural tube defects, asymptomatic bacteruria, Downs syndrome)
Pediatrics (PKU, sickle cell disease, visual impairment, lead intoxication, hearing loss, dental caries)
11. Case A 52 year old is concerned about her risk of ovarian and breast cancer. She has 2 children that were born vaginally after uneventful pregnancies. Menarche was at age 15 and she entered menopause at age 50. Her mother was diagnosed with breast cancer at age 62 and her paternal grandmother was diagnosed with breast cancer at age 70. Her mothers two sisters are both without cancer. At this time, the appropriate management is to
A) advise her to have a bilateral salpingo-oophorectomy
B) advise her to have genetic testing
C) measure CA-125 levels
D) order periodic transvaginal ultrasounds
E) recommend annual or biannual mammography
12. Breast cancer Epidemiology
Most common cancer in women
180,000 new cases projected for 2008
Risk factors: prior breast cancer, age, early menarche, delayed childbearing, HRT)
Second to lung cancer in cause of cancer death
Prevalence: Caucasians >> African Americans
Mortality: African Americans >> Caucasians
Breast cancer in men (~2,000 cases/year with 400 deaths/year)
(almost 1/3 of cancer diagnoses in women)
Family history: in first degree relative
(almost 1/3 of cancer diagnoses in women)
Family history: in first degree relative
13. Breast cancer
14. Breast cancer USPSTF recommendations
Screening mammography with or without clinical breast exam (CBE) every 1-2 years starting at age 40
Insufficient evidence for or against CBE alone
Insufficient evidence for or against teaching or performing routine self breast exams Evidence strongest for women ages 50-69, weaker for those aged <50
Evidence strongest for women ages 50-69, weaker for those aged <50
15. Breast cancer
16. Breast cancer Cost effectiveness:
Women aged 40-49: $105,000 per year of life saved10
Women aged 50-69: $21,400 per year of life saved
Results:
Reduction in total mortality as high as 65%
Despite these reductions, data from 2000?2005 show decreasing rates of mammography16
19. Breast Cancer Other recommendations:
AMA, ACOG, ACR, ACS: mammography and CBE
Ages 40-49: Every 1-2 years
Age 50 and above: Annually
AAFP, ACPM: mammography
Age 40: high risk women
Age 50: all women
ACR: (American College of Radiology),
ACS: (American cancer society)
AAFP: American Academy of Family Physicians
ACPM: American College of Preventive Medicine
ACR: (American College of Radiology),
ACS: (American cancer society)
AAFP: American Academy of Family Physicians
ACPM: American College of Preventive Medicine
20. Case A 51 year old woman comes to the ED with fever, chills, and LLQ pain. CT scan diagnoses diverticulitis and the patient is treated with ciprofloxacin and metronidazole. She has no significant past medical history, has regular menstrual periods, and has smoked 1 ppd x 15 years. Since she has no regular physician, she is scheduled to follow-up for a new patient evaluation and monitoring of her diverticulitis in 3 days. During her new patient evaluation she should be scheduled for:
A) a chest xray
B) a mammogram every year for the first 2 years, then every 5 years
C) a Pap smear
D) serum FSH/LH levels
E) yearly electrocardiogram
21. Cervical cancer Epidemiology
11,000 cases diagnosed annually
4,000 deaths
Found in women mostly age 20-50
Hispanic>>Black>>Caucasian
Overall 5-year survival rate 72%
Risk factors: HPV, Smoking, STDs
10th leading cause of cancer death 20% of diagnoses are women >6520% of diagnoses are women >65
22. Cervical cancer USPSTF recommendations
Recommends screening in women who are sexually active and have a cervix
Recommends against screening women > 65 years if they have negative screening history and no high risk behavior
Recommends against screening women who have had hysterectomy for benign disease
Insufficient evidence for new technologies to screen for cervical cancer
Insufficient evidence for HPV testing as a primary screen for cervical cancer
Recommends Screening:
Start within 3 years of first sexual activity or turning age 21
Screen at least every three years after 3 normal exams
New technologies: Liquid based cytology, computerized rescreening, algorithm based screening
Recommends Screening:
Start within 3 years of first sexual activity or turning age 21
Screen at least every three years after 3 normal exams
New technologies: Liquid based cytology, computerized rescreening, algorithm based screening
23. Cervical cancer Screening tests
Pap smear: 60-80% sensitivity, increases with repetitive screens
HPV screening: Sensitivity 66%, Specificity 91%
Combination HPV + Pap-sensitivity approaches 100%6
Mayrand trial: ~10,000 women screening with HPV vs PAP. Sensitivity of HPV 95.%, sensitivity of pap 55%. Together approached 100%. Part of the Canadian Cervical Cancer screening trial
However, this trial was sponsered by Merck, who came up with the gardasil vaccine!!!!!Mayrand trial: ~10,000 women screening with HPV vs PAP. Sensitivity of HPV 95.%, sensitivity of pap 55%. Together approached 100%. Part of the Canadian Cervical Cancer screening trial
However, this trial was sponsered by Merck, who came up with the gardasil vaccine!!!!!
24. Cervical cancer Cost-effectiveness:
$50,000/year of life saved (with screening every 3 years)
Results:
Reduced cervical cancer rates by 60-90%
92% survival rate for early disease
13% survival rate for late disease
25. Cervical cancer Other recommendations:
ACS:
onset-first sexual activity to age 21
annual screening until age 30, then every 3 years
ACOG, ACPM, AAFP, AMA, AAP:
onset-age 18
discontinue after 65-70 with 3 negative screens
26. Case A 43 yo man comes to the office requesting that little blue pill they show on tv. Upon review of his medical records, you see he has not been in the office for more than 2 years. He has a history of HTN and osteoarthritis. Family history is positive for colon cancer in his father at age 53 and HTN in his mother. He smokes 1ppd for more than 20 years. He denies any chest pain, shortness of breath, bowel or bladder changes. Blood pressure measured today is 132/87, blood sugar is 103. What is the most appropriate current intervention?
A) prescribe viagra and follow-up in 2 months
B) Refer for screening CXR for possible lung cancer
C) Check a Hemoglobin A1C
D) Refer for screening colonoscopy
E) Order renal artery scan for HTN
27. Colorectal cancer Epidemiology:
3rd most common cause of cancer in U.S.
3rd most common cause of cancer death
150,000 new cases/year, with 50,000 deaths
Risk factors:
family history of colorectal cancer (FAP, HNPCC)
ulcerative colitis
h/o adenomatous polyps
Obesity
low fiber diet At age 50, 5% chance developing colorectal cancer and 2.5% of dying from it, with average 13 years life lost
At age 50, 5% chance developing colorectal cancer and 2.5% of dying from it, with average 13 years life lost
28. Colorectal cancer USPSTF recommendations
Strongly recommends screening for men and women age 50 or older
Colonoscopy every 10 years
FOBT annually + flexible sigmoidoscopy every 5 years
No further screening after age 75 if negative screens since age 50
Testing 10 years before first diagnosed family member
29. Colorectal Cancer Sigmoidoscopy: 77% of colorectal cancer cases diagnosed at stage 1/2Sigmoidoscopy: 77% of colorectal cancer cases diagnosed at stage 1/2
30. Colorectal Cancer FOBT screening trials:3
Minnesota trial
13-year follow-up
18 year follow-up
Nottingham
Funen trial
Minnesota trial: 46,551 patients, randomized to annual, biennial or control group:
13 year : 33% mortality reduction annually, 6% biennial mortality reduction
18 year: 33% mortality reduction annually, 21% biennial mortality reduction, especially in Stage D cancer
Nottingham trial: 152, 850 participants15% mortality reduction with biennial screening (short f/u and low compliance with screening = limitations)
Funen trial: 61,933 participants, biennial screening, 18% mortality reduction (follow up 10 years, 56% compliance)Minnesota trial: 46,551 patients, randomized to annual, biennial or control group:
13 year : 33% mortality reduction annually, 6% biennial mortality reduction
18 year: 33% mortality reduction annually, 21% biennial mortality reduction, especially in Stage D cancer
Nottingham trial: 152, 850 participants15% mortality reduction with biennial screening (short f/u and low compliance with screening = limitations)
Funen trial: 61,933 participants, biennial screening, 18% mortality reduction (follow up 10 years, 56% compliance)
31. Colorectal cancer Cost-effectiveness:
$30,000/year of life saved
Varied studies which strategy is most cost-effective
Results:
Cure rate with early screening approaches 90%
271 years of life gained for every 1000 screens (colonoscopy)
199 years life gained for every 1000 screens (flex sig)
32. Colorectal cancer Other recommendations
ACS, U.S. Multi-Task force on Colorectal Cancer, ACR:
Screening at age 50 (annual FOBT vs. flex-sig/barium enema/CT colonography every 5 years vs. colonoscopy every 10 years
ACOG:
colonoscopy as preferred source
33. Case With respect to prostate cancer, which of the following is true?
A) A serum PSA of 4ng/dl is diagnostic of prostate cancer
B) Prostate cancer is the most common non-skin cancer in men
C) African-Americans and Caucasians have the same incidence of prostate cancer
D) Prostate is the most common cause of cancer death in men
E) The American Cancer Society recommends all men begin prostate cancer screening at age 30
34. Prostate cancer Epidemiology:
1 in 6 men will be diagnosed
218,000 cases/year, with ~23,000 deaths annually
Median age of death ~80 years
African Americans >>Caucasians in terms of incidence and mortality
Overdiagnosis as high as 45% by PSA screen
35. Prostate Cancer USPSTF recommendations
Insufficient evidence to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75
Recommends against screening for prostate cancer in men > 75
36. Prostate Cancer Screening tests:
PSA
Sensitivity: 40-60% vs 91% (aggressive cases)
Can be falsely elevated by BPH/prostatitis
75% of men with PSA 4-10 do not have cancer
DRE
Largely unknown statistics with and without PSA
37. Prostate Cancer Cost-effectiveness:
Limited studies
May have increased benefit if PSA checked every 2 years rather than 1 year2
Screening q 2 years: (may reduce number of screens by 50% while retaining 93% of years of life saved (PSA >4)Screening q 2 years: (may reduce number of screens by 50% while retaining 93% of years of life saved (PSA >4)
38. Prostate cancer Other recommendations:
AAFP, ACOP, ACPM, AMA:
recommend screening men > age 50 with life expectancy of at least 10 years
ACS, American Urological Association:
Recommend annual PSA/DRE for men > age 50
39. Case A 56 yo woman with a history of smoking 1ppd for 32 years presents to her primary care physician for routine follow-up. She has no medical problems, and denies chest pain, shortness of breath, cough, hemoptysis, fever, and weight loss. Her husband who arrived with her asks you if it would be possible to get her tested for lung cancer given her extensive smoking history. At this point you would recommend.
A) 3 consecutive sputum samples for cytology
B) A chest xray today, then every six months
C) No current screening as she is asymptomatic
D) A chest xray every year after she turns 40
E) A high resolution chest CT given her extensive smoking history
40. Lung Cancer Epidemiology:
2nd leading cause but highest cancer mortality for both men and women
2008 projections: 215,000 cases diagnosed, 161,000 deaths
Survival: 60-70% for Stage 1 disease, 5-15% for Stage 4 disease
Risk factors: active/passive tobacco exposure, asbestos exposure, IPF, COPD, family history, environmental exposures (i.e. radon)
41. Lung Cancer USPSTF recommendations:
Evidence is insufficient to recommend for or against screening in asymptomatic persons for lung cancer with either CXR, CT chest or sputum cytology
42. Lung Cancer Screening tests:
CXR: Sensitivity 26%, Specificity 93%
LDCT (Low Dose Computerized Tomography): False positive rate approaches 41%
Increased cost, higher radiation exposure
I-ELCAP trial9
Sputum cytology: unknown, most trials done in the setting of concomitant CXR
I-Elcap: The International Early Lung Cancer Action Program
31,567 asymptomatic patients screened with low dose CT. 1993-2005. 484 patients diagnosed with lung cancer (mostly stage 1) with 10 year survival 88%, increased to 92% after surgical resection within 1 month. 8 pts with clinical stage 1 cancer who did not receive screenigng died within 5 years
Limitations include: no control group (of non-screened people), harms of screening not discussed. Lead time bias (tumors detected earlier). CT screening more sensitivye for periheral disease *which are usually adenocarcinomas and have a better prognosis anyway. Was an observational study.
Criticisms: Although the trial improved survival in those 484 pts screened and treated, the overall mortality of the entire group did not decrease. Also an overdiagnosis bias, the harms of overdiagnosing clinically irrevelant tumors were not addressed.I-Elcap: The International Early Lung Cancer Action Program
31,567 asymptomatic patients screened with low dose CT. 1993-2005. 484 patients diagnosed with lung cancer (mostly stage 1) with 10 year survival 88%, increased to 92% after surgical resection within 1 month. 8 pts with clinical stage 1 cancer who did not receive screenigng died within 5 years
Limitations include: no control group (of non-screened people), harms of screening not discussed. Lead time bias (tumors detected earlier). CT screening more sensitivye for periheral disease *which are usually adenocarcinomas and have a better prognosis anyway. Was an observational study.
Criticisms: Although the trial improved survival in those 484 pts screened and treated, the overall mortality of the entire group did not decrease. Also an overdiagnosis bias, the harms of overdiagnosing clinically irrevelant tumors were not addressed.
43. Lung Cancer Cost-effectiveness:
$2,500 per person/year of life saved
Additional health care costs of $116,300 per quality-adjusted life year gained
Results:
78-82% Stage 1 detection for CT screening
NO improvement in mortality
Significant overdiagnosis of non-relevant tumors
Future: National Lung Cancer Screening Trial Sponsored by National Cancer Institute from 2002-2004 enrolling 50,000 patients randomized to CXR or CT screening with results expected in 8-10 years
Sponsored by National Cancer Institute from 2002-2004 enrolling 50,000 patients randomized to CXR or CT screening with results expected in 8-10 years
44. Lung Cancer Other recommendations:
American College of Chest Physicians:
recommends against screening other than in setting of a clinical trial
ACS:
Informed individual decision making. If testing is chosen, spiral CT only in centers with multidisciplinary teams
AAFP:
No screening for asymptomatic persons
45. Whats next? PLCO trial (Prostate, Lung, Colorectal and Ovarian cancer screening trial)
1992-2001 (13 years planned f/u)
>150,000 subjects
Checks: PSA, DRE, flex sig, CXR, CA-125, transvaginal u/s
Most published data has been prostate
46. References
1 )Barry et al. Prostate Specific Antigen testing for early diagnosis of Prostate Cancer. New England Journal of Medicine. May 3, 2001. Volume 344. 1373-1377.
2) Etzioni et al. Serial Prostate Specific Antigen screening for Prostate Cancer: A computer model evaluates competing strategies. The Journal of Urology. Sept 1999. Volume 162. pg 748
3) Mandel, J. et al. Colorectal Cancer Mortality: Effectiveness of Biennial Screening for Fecal Occult Blood. Journal of the National Cancer Institute.1999. pgs 434-437.
4) Mandelblatt, J et al. The Cost-Effectiveness of Screening Mammography Beyond age 65. Annals of Internal Medicine. 2003. Vol. 139. pgs 835-842
5) Manser et al. Screening for lung cancer (Review). The Cochrane Collaboration. 2008.
6) Mayrand, M.H. et al. Human Pappilomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer. The New England Journal of Medicine. October 2007. Vol. 357. pgs 1579-1588.
7) Mulshine and Sullivan. Lung Cancer Screening. New England Journal of Medicine. 2005. Volue 352. pgs2714-2720.
8) Patz et al. Screening for lung cancer. New England Journal of Medicine. Nov. 30 2000. Volume 343. pgs 1627-1633.
9) Ross. K. S. et al. Comparative Efficiency of Prostate Specific Antigen screening strategies for prostate cancer detection. Journal of the American Medical Association. 2000. Vol. 284. pgs 1399-1405.
10) Salzmann et al. Cost-effectiveness of extending screening mammography guidelines to include women 40-49 years of age. Annals of Internal Medicine. Dec. 1 1997. pgs 955-965.
11)The International Early Lung Cancer Action Program Investigators. Survival of Patients with Stage 1 Lung Cancer Detected on CT screening. The New England Journal of Medicine. 2006. Vol 355. Pgs 1763-1771.
12) Thompson et al. Prevalence of prostate cancer among men with a Prostate specific antigen level of less than or equal to 4 ng/milliliter. New England Journal of Medicine. May 27, 2004. Vol. 350.
13) Whitlock et al. Screening for colorectal cancer: A targeted, updated systematic review for the U.S Preventiv Services Task Force. Annals of Internal Medicine. Nov. 4, 2008. Vol. 149.
14) Weissfeld, J. et al. Flexible Sigmoidoscopy in the PLCO Cancer Screening Trial: Results from the Baseline Screening Examination of a Randomized Trial. Journal of the National Cancer Institute. 2005. p 989-997
Websites:
15) USPSTF: http://www.ahrq.gov/clinic/USpstfix.htm
16) American Cancer Society: www.cancer.org
17) National Cancer institute: http://www.cancer.gov/
18) Uptodate: http://www.utdol.com