Transcript Cancer Screening in Women - UCLA Med-Peds

Cancer Screening in
Women… Update
Jodi Friedman, MD
David Geffen School of
Medicine at UCLA
Principles of Prevention
FIRST DO NO HARM!
– asymptomatic, by definition
– predominantly healthy population
– evidence-based medicine
Principles of Prevention
Where do Preventive Services recommendations
come from?
 USPSTF, CTFPHC
• extensive review of literature
• rigorous requirements of proof of efficacy
 Various subspecialty organizations
What the USPSTF Grades Mean and Suggestions for
Practice
Ann Intern Med 2009;151:716-726
©2009 by American College of Physicians
Principles of Screening
Appropriateness of a screening test
• the disease
• the test
• the population
Potential Adverse Effects
of Screening
– physical complications of the test
– consequences of false positives
• anxiety
• complications from work-up
• labeling/insurability
– over treating insignificant abnormalities
– financial costs
Screening
 Cervical Cancer
 Breast Cancer
 Colorectal Cancer
 Lung Cancer
 Ovarian Cancer
Cervical Cancer Screening
 Since early 1970’s, mortality has
decreased 74%
 Largely attributable to screening with the
Pap smear
 Majority of disease now occurs in
women with inadequate screening
Cervical Cancer
 Progression: HPV infxn  high grade lesion
 invasive disease
 On average, initial HPV infxn to invasive
cancer takes 10-20 years
 Lifetime risk of acquiring at least 1 HPV infxn
estimated as high as > 90%
 Majority of these infections are transient
Cervical Cancer
 Over 100 HPV types, 13 are associated with cervical
intraepithelial neoplasia
 Most HPV infxns never progress beyond low grade
disease (CIN 1)
• Women 15-25 years of age ~ 80% of HPV
infections are transient
 80 -90% of low grade cervical abnormalities will
regress spontaneously
HPV Testing
 2 commercially available assays for the
“oncogenic” HPV types
 These 13 types account for ~ 90% of
HPV types associated with HSIL and
cervical cancer
HPV Testing
 Most established role of testing is to
“triage” ASCUS results
• HPV + : double the probability of
HSIL (15%)
• HPV - : less than 1% chance of HSIL
 Role in primary screening less wellestablished
Current Recommendations
 USPSTF (2003)
• begin w/in 3 yrs of first sexual activity or 21
yo, whichever first
• after 2-3 normal annual Paps, screen every 3
yrs
• in women who have had adequate screening
(3 Paps in preceding 10 years) stop at 65
• no screening if hysterectomy for benign
causes
Current Recommendations
 ACS (2009)
• begin w/in 3 yrs of first sexual activity or 21 yo,
whichever first
• annual Paps until age 30 (or q 2 yrs with liquidbased cytology)
• after 3 normal annual Paps
• may begin every 2-3 yr screening
• may opt for HPV and Pap testing every 3 years
• annual screening if HIV, DES exposure, or
significant immunosuppression
• if adequate screening, stop at 70
Current Recommendations
 ACOG (11/2009)
• begin at age 21
• every 2 years Paps until age 30
• Age 30 and older, after 3 consecutive normal Paps
should be screened once every 3 years
• annual screening if HIV, DES exposure, or
significant immunosuppression
• may stop at 65 – 70 if
• 3 negative cytology results in a row
• No abnormal test in the past 10 years
Breast Cancer
 Most prevalent cancer in women
 Second leading cause of cancer deaths
 Average lifetime risk of developing breast
cancer is 1 in 8
• 40’s: 1 in 69
• 50’s: 1 in 38
• 60’s: 1 in 27
Breast Cancer Screening
 Breast Self Exam
 Clinical Breast Exam
 Mammography
 MRI
Breast Self Exam (BSE)
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
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2 RCT’s, 1 large non-RCT
F/U 5-13 yrs
No reductions in mortality
No significant improvement in # or stage of
cancers detected
 2-fold increase in biopsies (benign) in BSE
grps
Clinical Breast Exam
 No direct evidence comparing CBE alone to no
screening
 Reductions in mortality observed when used with
mammography
 Reductions in mortality in mammography trials alone
similar to that using CBE with mammography
Mammography
 Positive predictive value
• Aged 40-49: 1-4%
• Aged 50-59: 4-9%
• Aged 60-69: 10-19%
• 70 and over: 18-20%
Mammography
 9 RCTs: 0-32% mortality reduction
 Meta-analysis shows:
• 50 yo and over: RR = 0.78 (CI, .70-.87)
• 22% reduction in breast cancer mortality
• 40-49 yo: RR=0.85 (CI, .77-.97)
• 15% reduction in breast cancer mortality
 Only 1 study included women up to 74 yo
• No statistically significant benefit in women 70-74 but
numbers small
Pooled relative risk for breast cancer mortality from mammography screening
trials compared with control for women aged 39 to 49 years.CNBSS-1 = Canadian
National Breast Screening Study-1; CrI = credible interval; HIP = Health Insurance
Plan of Greater New York.* Swedish Two-County trial.
Nelson H D et al. Ann Intern Med 2009;151:727-737
©2009 by American College of Physicians
NNI to Prevent 1 Breast
Cancer Death
 39 – 49 yo
1904
 50 – 59 yo
1339
 60 – 69 yo
377
Frequency of Mammographic
Screening
 Trials range from 12-33 month intervals
 Decision analysis study (USPSTF)
• Biennial screening produced 81% of
the benefit of annual screening
• Half the number of false positives and
unnecessary biopsies
MRI
 14 prospective trials in hi-risk women (2080% lifetime risk)
 No studies have demonstrated MRI reduces
risk of death from breast cancer
 Sensitivity 71-100%
• vs. 16-40% with mammo or utz
 Specificity 81 – 97%
• vs. 93 -99% with mammo
USPSTF Breast Cancer Screening
Recommendations (2009)
 The USPSTF recommends biennial screening
mammography for women aged 50 to 74 years.
Grade: B recommendation.
 The decision to start regular, biennial screening
mammography before the age of 50 years should be an
individual one and take patient context into account,
including the patient's values regarding specific benefits
and harms.
Grade: C recommendation.
USPSTF Breast Cancer Screening
Recommendations (2009)
 The USPSTF concludes that the current evidence
is insufficient to assess the additional benefits and
harms of screening mammography in women 75
years or older.
Grade: I Statement.
 The USPSTF recommends against teaching breast
self-examination (BSE).
Grade: D recommendation.
USPSTF Breast Cancer Screening
Recommendations (2009)
 The USPSTF concludes that the current evidence is
insufficient to assess the additional benefits and harms of
clinical breast examination (CBE) beyond screening
mammography in women 40 years or older.
Grade: I Statement.
 The USPSTF concludes that the current evidence is
insufficient to assess the additional benefits and harms of
either digital mammography or magnetic resonance
imaging (MRI) instead of film mammography as screening
modalities for breast cancer.
Grade: I Statement.
Other Groups’
Recommendations
 AAFP (2009) – all recommendations in
agreement with new USPSTF
guidelines
 ACS
• Begin annual mammography at 40
• CBE q 3 yr 20-40, yearly after 40
• BSE option, beginning at 20
Screening Recommendations:
MRI
 ACS now recommends annual MRI (in
addition to mammo) for women with
lifetime risk estimate at least 20-25%
 Also recommended for women with h/o
chest irradiation for HD
 ? When to begin
 ? Personal h/o breast CA, LCIS, ADH
ASCO Screening
Recommendations for High-Risk
Women
 Screening breast MRI appears to be more
sensitive than mammography in high-risk
women
 BRCA 1/2 carriers should be screened with
annual MRI, mammography and possibly
ultrasound
 The decision to use breast MRI in high-risk
patients should be made on an individual
basis
Colorectal Cancer (CRC)
 Third leading cause of cancer deaths
 Lifetime incidence is 5%, lifetime
mortality is 2.5%
• 1 first-degree relative, RR=1.7
• 2 first-degree relatives, RR=2.7
 Highest risk - familial polyposis
syndromes and long-standing UC
Fecal occult blood testing
(FOBT)
 4 RCTs – all show mortality benefit
• Over 46,000 subjects ages 50-80
• annual FOBT v. no screening
• 33% reduction in CRC mortality
• Biennial FOBT ages 45-74
• 15% - 18% reduction in mortality
Flexible Sigmoidoscopy
 2 large case-control studies - 60% reduction in
risk of death from CRC
 1 RCT – showed increased detection rate of
adv neoplasms and cancers compared to
FOBT
 Detects approx 50% of CRCs and
adenomatous polyps
• up to 3% of pts screened will have advanced
neoplasm that sigmoidoscopy will miss
Colonoscopy
 No RCTs
 Identification and removal of adenomas is the
central element of reducing CRC incidence
and mortality
 One case-control study showed odds ratio for
CRC mortality was 0.43
 All other screening strategies include
colonoscopy
Screening Recommendations
(2008)
 The USPSTF recommends screening for colorectal cancer
(CRC) using fecal occult blood testing, sigmoidoscopy, or
colonoscopy, in adults, beginning at age 50 years and
continuing until age 75 years. The risks and benefits of
these screening methods vary.
Grade: A Recommendation
 The USPSTF recommends against routine screening for
colorectal cancer in adults age 76 to 85 years. There may
be considerations that support colorectal cancer screening
in an individual patient.
Grade: C Recommendation
Screening Recommendations
(2008)
 The USPSTF recommends against screening for
colorectal cancer in adults older than age 85 years.
Grade: D Recommendation
 The USPSTF concludes that the evidence is
insufficient to assess the benefits and harms of
computed tomographic colonography and fecal
DNA testing as screening modalities for colorectal
cancer.
Grade: I Statement.
CRC Screening
 Most groups agree that any strategy patient
agrees to should be offered:
• annual FOBT
• sigmoidoscopy q 5 ys
• annual FOBT + flex sig q 5 yrs
• colonoscopy q 10 yrs
 CRC screening is cost-effective at less than
$30K per year saved regardless of strategy
Lung Cancer
 Leading cause of cancer-related death among
women and men in the US.
 Average 5-yr survival rates < 15%
• 70% for stage I
• < 5% for stage IV
 USPSTF 1996 recommended against
screening based on RCT data of CXR and
sputum cytology screening
CXR +/- Sputum Cytology
 6 RCTs (men only)
• varying screening intervals
• no benefit to those screened
• all studies limited by some level of
screening in control groups
Mortality in randomized, controlled trials of lung cancer screening with chest radiography
with or without sputum cytologic examination.
Humphrey L L et al. Ann Intern Med 2004;140:740-753
©2004 by American College of Physicians
Low Dose CT (LDCT)
 Sensitivity 4 times greater than CXR
 8 cohort studies using LDCT
• lung cancer diagnosed at earlier stage
• high rate of FPs
• cannot evaluate mortality outcomes
without control groups
Low Dose CT (LDCT)
 RCTs
• National Lung Screening Trial (NCI)
• LDCT vs. CXR
• NELSON Trial (Dutch study)
• LDCT vs. no screening
National Lung Screening Trial
 RCT
• >53,000 current or former heavy smokers
• Age 55 – 74
• 3 annual screenings with LDCT vs. CXR
• 90% statistical power to detect 20%
mortality reduction
National Lung Screening Trial
 On October 28, 2010 the DSMB stopped
the trial
 A 20% reduction in lung cancer deaths
was found in the LDCT screened group
 6.9% reduction in all-cause mortality
(secondary endpoint)
 Await full publication of the results
USPSTF May, 2004
 I Recommendation
 fair evidence that screening with LDCT, CXR, or sputum
cytology can detect lung cancer at an earlier stage than lung
cancer would be detected in an unscreened population
 poor evidence that any screening strategy for lung cancer
decreases mortality
 because of the invasive nature of diagnostic testing and the
possibility of a high number of false-positive tests in certain
populations, there is potential for significant harms from
screening
Ovarian Cancer
 Fifth leading cause of cancer-related death in
women
 Low incidence in general population
• overall incidence is 17 per 100,000
• in women over 50, 44 per 100,000
 for average risk women, an abnormal
screening test will have a 1-4% positive
predictive value
Ovarian Cancer Screening
 Screening is Problematic
• Low PPV (low prevalence)
• High mortality
• No well-defined precursor lesion
• FPs lead to serious morbidity
Ovarian Cancer Screening
 CA-125
 Transvaginal Ultrasound
 16 Fair-poor quality cohort studies:
• Sensitivities 80-100%
• False positives .6-2.5%
Ovarian Cancer Screening
 1 RCT of multimodal screening
• non-statistically signif improvement in stage
1 detection (50% vs. 5%)
 2 large cohort studies of UTZ
• 59-65% diagnosed in stage 1
 No evidence that detecting early stage cancer
through screening decreases mortality
 3 RCTs in progress to evaluate mortality
Ovarian Cancer Screening
 USPSTF (2004): D recommendation
 There is no existing evidence that any screening test,
including CA-125, ultrasound, or pelvic examination, reduces
mortality from ovarian cancer
 existing evidence that screening can detect early-stage ovarian
cancer is insufficient to indicate that this earlier diagnosis will
reduce mortality
 Because of the low prevalence of ovarian cancer and the
invasive nature of diagnostic testing after a positive screening
test, there is fair evidence that screening could likely lead to
important harms
Ovarian Cancer Screening
 Routine screening NOT recommended by any
professional organization
 ACS
• hi-risk women may benefit from screening
with CA-125 and UTZ
 ACOG
• stay vigilant for early sxs and w/u when
present
Bibliography
 Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural
history of cervicovaginal papillomavirus infection in young
women. N Engl J Med 1998;338:423–8.
 Mark E. Sherman , et.al. Baseline Cytology, Human
Papillomavirus Testing, and Risk for Cervical Neoplasia: A
10-Year Cohort Analysis JNCI Journal of the National Cancer
Institute 2003 95(1):46-52
 Screening for Cervical Cancer, Topic Page. January 2003.
U.S. Preventive Services Task Force. Agency for Healthcare
Research and Quality, Rockville, MD.
http://www.ahrq.gov/clinic/uspstf/uspscerv.htm
Bibliography
 HD Nelson et al. Screening for Breast Cancer: An Update for
the U.S. Preventive Services Task Force. Ann Intern Med
2009;151:727
 USPSTF. Screening for breast cancer: U.S. Preventive
Services Task Force recommendation statement. Ann Intern
Med 2009;151:716
 Screening for Breast Cancer, Topic Page. November
2009. U.S. Preventive Services Task Force. Agency
for Healthcare Research and Quality, Rockville, MD.
http://www.ahrq.gov/clinic/uspstf/uspsbrca.htm
Bibliography
 Screening for Colorectal Cancer, Topic Page.
March 2009. U.S. Preventive Services Task
Force. Agency for Healthcare Research and
Quality, Rockville, MD.
http://www.ahrq.gov/clinic/uspstf/uspscolo.ht
m
Bibliography
 The International Early Lung Cancer Action Program
Investigators. Survival of patients with stage I lung
cancer detected on CT screening. N Engl J Med
2006;355:1763-1771
 Computed Tomography Screening and Lung Cancer
Outcomes
Peter B. Bach; James R. Jett; Ugo Pastorino; Melvyn
S. Tockman; Stephen J. Swensen; Colin B. Begg
JAMA. 2007;297:953-961.
Bibliography
 Lung Cancer Screening, Topic Page. May 2004. U.S.
Preventive Services Task Force. Agency for
Healthcare Research and Quality, Rockville, MD.
http://www.ahrq.gov/clinic/uspstf/uspslung.htm
 Screening for Ovarian Cancer, Topic Page. May
2004. U.S. Preventive Services Task Force. Agency
for Healthcare Research and Quality, Rockville, MD.
http://www.ahrq.gov/clinic/uspstf/uspsovar.htm