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					Cancer screening
Bindu Shah Senior Talk 2008

Case
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A 52 y.o woman presents to her primary care physician’s 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?

Objectives
After attending this lecture, participants will be able to…
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Define a screening test and its uses/pitfalls in ambulatory practice Describe the United States Preventive Services Task Force and interpret its levels of recommendations 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

What is the USPSTF?
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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)

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USPSTF

http://www.ahrq.gov/clinic/USpstfix.htm

Screening tests
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A test for a particular disease given to patients who have no symptoms
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Should be an important, morbid health condition Generally cheap Highly sensitive Not too demanding or risky There should be a treatment

Screening tests
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Universal screening
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Screening all individuals of a certain category (e.g. PKU screening in kids)

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Case finding
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Screening a small group of individuals based on the presence of risk factors (e.g cancer clusters, family members diagnosed with hereditary disease)

Screening tests
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Adverse effects
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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

Screening tests
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Biases
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Lead time bias Length time bias Selection bias Overdiagnosis bias

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Avoid bias by using Randomized Control Trials (RCTs)

Commonly screened diagnoses
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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, Down’s syndrome) Pediatrics (PKU, sickle cell disease, visual impairment, lead intoxication, hearing loss, dental caries)

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 mother’s 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

Breast cancer
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Epidemiology
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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)

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Breast cancer

Source: U.S cancer statistics working group, 2007

Breast cancer
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USPSTF recommendations
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Screening mammography with or without clinical breast exam (CBE) every 1-2 years starting at age 40 Insufficient evidence for or against CBE alone

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Insufficient evidence for or against teaching or performing routine self breast exams

Breast cancer
Sensitivity
Mammography 77-95% Clinical breast exam 40-69%

Specificity
3-6% 86-99%

Self breast exam

26-41%

Unknown

Breast cancer
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Cost effectiveness:
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Women aged 40-49: $105,000 per year of life saved10 Women aged 50-69: $21,400 per year of life saved

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Results:
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Reduction in total mortality as high as 65% Despite these reductions, data from 20002005 show decreasing rates of mammography16

Summary of Studies on the Cost-Effectiveness of Screening for Breast Cancer after Age 654

Author, Year, Reference Messecar, 2000

Interval Biennial

Mammography Effectiveness SEER stage distributionc

Cost Cost-Effectiveness Ratio Screen Diagnosis Treatment $118 $1,294 $40,475 3.3 days saved for screening ages 75 -79 (vs ages 65-74) healthy women; 1.5 days saved for women with dementia; cannot abstract CE ratio

Rosenquist and Lindfors, 1998

Annual ages 40-49, biennial ages 50-79

39% reduction in mortality with biennial for 50+; 13% for 40-49 yrs

$72

$1,116

$7,991 (surgery only)

$22,794-$27,248 average CE of screening for ages 50-79d

Lindfors and Rosenquist, 1995

Annual ages 40-49, biennial ages 50-79

Mortality reduction varies by age; 4%23% for ages 4049; 23%-32% for ages 60-79

$110

$1,116

$7,991 (surgery only)

$50,131 for biennial at ages 65-79 (approx vs stopping at age 59)e

Brown, 1992

Biennial

Observed from RCTs ~30% reduction in mortality

$99

$2,520

Medicare costs: $21,287 local; $30,714 regional; $30,714 distant; $63,455 terminal care

$50,400 for ages 70-75 vs ages 65-70; $54,000 for ages 75-80 vs ages 70-75

Boer et al, 1998

Biennial; examines triennial Biennial; examines annual and triennial Biennial

Observed from RCTs ~30% reduction in mortality Observed from RCTs ~30% reduction in mortality Observed from RCTs ~30% reduction in mortality Unknown

$66

National Health Service costs National Health Service costs

$34,860 advanced stage $34,860 advanced stage

$5,910 for ages 65-69 vs stopping at age 64 $48,433 for ages 65-94 vs ages 50-64

Boer et al, 1999

$66

de Koning et al, 1991

$66

National Health Service costs Medicare costs: $21,287 local; $30,714 regional;

$34,860 advanced stage Medicare costs: $21,287 local; $30,714 regional;

$13,280 for ages 71-75 vs ages 65-70 $34,188-$86,614 for screening for ages 65-75

Eddy, 1989

Annual

$194

$30,714 distant;

$30,714 distant; $63,455 terminal care

$63,455 terminal care Kerlikowske et al, 1999 Biannual 27% reduction in mortality (22%32%); assume benefits continue for 5 yrs after cessation of screening Based on $108$138 $451 Kaiser HMO costs: $31,258 DCIS; $45,220 $87,887 for ages 70-79 vs stopping at age 69

Mandelblatt et al, 1992

1 point in annual program

$146

N/A

N/A

Varies by age and health group

Breast Cancer
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Other recommendations:
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AMA, ACOG, ACR, ACS: mammography and CBE
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Ages 40-49: Every 1-2 years Age 50 and above: Annually

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AAFP, ACPM: mammography
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Age 40: high risk women Age 50: all women

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

Cervical cancer
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Epidemiology
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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, STD’s
10th leading cause of cancer death

Cervical cancer
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USPSTF recommendations
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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

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Cervical cancer
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Screening tests
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Pap smear: 60-80% sensitivity, increases with repetitive screens HPV screening: Sensitivity 66%, Specificity 91%
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Combination HPV + Pap-sensitivity approaches 100%6

Cervical cancer
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Cost-effectiveness:
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$50,000/year of life saved (with screening every 3 years)

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Results:
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Reduced cervical cancer rates by 60-90% 92% survival rate for early disease 13% survival rate for late disease

Cervical cancer
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Other recommendations:
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ACS:
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onset-first sexual activity to age 21 annual screening until age 30, then every 3 years

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ACOG, ACPM, AAFP, AMA, AAP:
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onset-age 18 discontinue after 65-70 with 3 negative screens

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

Colorectal cancer
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Epidemiology:
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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

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Risk factors:
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family history of colorectal cancer (FAP, HNPCC) ulcerative colitis h/o adenomatous polyps Obesity low fiber diet

Colorectal cancer
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USPSTF recommendations
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Strongly recommends screening for men and women age 50 or older
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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

Colorectal Cancer
Sensitivity DRE/Office FOBT Barium Enema 40% 86-90% Specificity 96-98% 95%
based on

Colonoscopy
CTColonography

75-90%
polyp size

Unknown
Unknown

85-90%

based on polyp size/examiner experience

*Sigmoidoscopy: high sensitivity as any significant findings will be verified further by colonoscopy14

Colorectal Cancer
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FOBT screening trials:3
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Minnesota trial
13-year follow-up  18 year follow-up
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Nottingham Funen trial

Colorectal cancer
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Cost-effectiveness:
$30,000/year of life saved Varied studies which strategy is most cost-effective

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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)

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Colorectal cancer
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Other recommendations
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ACS, U.S. Multi-Task force on Colorectal Cancer, ACR:
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Screening at age 50 (annual FOBT vs. flex-sig/barium enema/CT colonography every 5 years vs. colonoscopy every 10 years colonoscopy as preferred source

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ACOG:
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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

Prostate cancer
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Epidemiology:
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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

Prostate Cancer
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USPSTF recommendations
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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

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Prostate Cancer
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Screening tests:
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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
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DRE
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Largely unknown statistics with and without PSA

Prostate Cancer
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Cost-effectiveness:
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Limited studies May have increased benefit if PSA checked every 2 years rather than 1 year2

Prostate cancer
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Other recommendations:
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AAFP, ACOP, ACPM, AMA:
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recommend screening men > age 50 with life expectancy of at least 10 years

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ACS, American Urological Association:
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Recommend annual PSA/DRE for men > age 50

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

Lung Cancer
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Epidemiology:
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2nd leading cause but highest cancer mortality for both men and women 2008 projections: 215,000 cases diagnosed, 161,000 deaths

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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)

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Lung Cancer
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USPSTF recommendations:
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Evidence is insufficient to recommend for or against screening in asymptomatic persons for lung cancer with either CXR, CT chest or sputum cytology

Lung Cancer
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Screening tests:
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CXR: Sensitivity 26%, Specificity 93%
LDCT (Low Dose Computerized Tomography): False positive rate approaches 41%
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Increased cost, higher radiation exposure I-ELCAP trial9

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Sputum cytology: unknown, most trials done in the setting of concomitant CXR

Lung Cancer
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Cost-effectiveness:
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$2,500 per person/year of life saved Additional health care costs of $116,300 per qualityadjusted life year gained

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Results:
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78-82% Stage 1 detection for CT screening NO improvement in mortality Significant overdiagnosis of non-relevant tumors

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Future: National Lung Cancer Screening Trial

Lung Cancer
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Other recommendations:
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American College of Chest Physicians:
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recommends against screening other than in setting of a clinical trial

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ACS:
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Informed individual decision making. If testing is chosen, spiral CT only in centers with multidisciplinary teams

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AAFP:
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No screening for asymptomatic persons

What’s next?
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PLCO trial (Prostate, Lung, Colorectal and Ovarian cancer screening trial)
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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

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 15791588. 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


				
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