Breast, Colon and Prostate Cancer Screening Guidelines and Questions Brandon S. Dickey

Breast, Colon and Prostate Cancer
Screening Guidelines and Questions
Brandon S. Dickey
October 30th, 2010
Indiana ACP Meeting
1. Discuss current guidelines for breast cancer
2. Discuss the current guidelines for colon
cancer screening
3. Discuss the current guidelines for prostate
cancer screening
4. Identify the appropriate populations for
cancer screening
• All three cancer screening guidelines have
undergone change or questions of efficacy
– Breast cancer
• Age of Screening?
– Colon Cancer
• Modalities that are recommended/accepted?
– Prostate Cancer
• Questions about EVERYTHING
• Rationale for screening
• Major changes discussion
• Recommendation from…
– United States Preventative Services Task Force
– American Cancer Society (ACS)
– Organization regarding specific disease state
Why are there so many guidelines
• Many of the expert groups have their own
– Diagnose no-matter-what mentality (ACS/professional
– Population based medicine (skews towards USPSTF)
– Concentrate on the harms of overdiagnosis (skews
towards USPSTF)
• Different vantage points create different
interpretations of data and what should be done
• Population-based Medicine vs. Individual-based
Target Patient Population
• AVERAGE risk patients
• High risk patients in each category would
require a completely different discussion
Breast Cancer Screening
• Approx. 192,000 of women are diagnosed each
– 40,200 die annually
• Increase of incidence in the 90s are largely due to
• Mortality rate since the 90s have decreased by an
average of 2.1 percent annually
– Likely due to screening and advances in treatments
– Mammograms are postulated to contribute about 28
to 65% to the decline
Screening Modalities
• Imaging and palpation are the modalities for
breast cancer diagnosis
• Imaging
– Film mammography
– Full-field digital mammography
– Breast MRI
• Palpation
– Clinical breast examination (CBE)
– Self breast examination (SBE)
Film Mammography
• Definitely can detect early breast cancers
– Between 1996 and 2001
• Breast biopsy performed on 1.6 percent of all
mammograms in the U.S.
• Cancer detected in 0.53 percent of mammograms
• 78 percent of invasive cancers diagnosed were lymph
node negative
Mortality Data for Mammograms
• Systematic review pooled relative risk data from 8
different studies (mortality from breast cancer)
– 39-49 year olds: 0.85 (95% CI 0.75 – 0.96)
– 50-59 year olds: 0.86 (95% CI 0.75 – 0.99)
– 60-69 year olds: 0.68 (95% CI 0.54 – 0.87)
• There is no doubt that film mammography is a
significant benefit
• No good studies available for all-cause mortality
Full-Field Digital Mammography
• Similar to traditional film-screen except the
image is digitalized
• Found to have similar detection rates
– More accurate for premenopausal and
perimenopausal women and women with denser
• Cost is between 3-5 times as much as film
Breast MRI
• Sensitivity of MRI is higher than
• Specificity of MRI is worse than that of
• ACS recommends use of breast MRI in setting
of high risk patients (greater than 20 – 25
percent lifetime risk)
Question of the Day
• When do we start screening and how often do
we screen?
• Observational study comparing mammogram
screening annually vs. biennually showed no
statistical significance in breast cancer
detection rate or prognostic stage
When to Initiate
• In 2009, the USPSTF released their
recommendations on breast cancer screening
– These recommendations took into an account of
data published in the Annals of Internal Medicine
– This data shed some light on screening between
40 – 49
• Comparing the age groups 40s to 50s
– Relative risk reduction in both are nearly identical
• 15% reduction in breast cancer mortality
– Prevalence of breast cancer is higher in 50s age
– Breasts are more dense in the 40s age group
• Leads to more false positives
More Stats
• Number needed to screen to prevent one
death from breast cancer
– Women in their 40s – 1904 need to be screened
– Women in their 50s – 1339 need to be screened
– Women in their 60s – 377 need to be screened
About the Benjamins
• Cost effectiveness analysis
– $21,400 per year of life saved for women ages 50
to 69
– $105,000 for women in their 40s
• Both values are generally accepted as cost
Model Analysis
• Annals 2009 published a model analysis of
different breast cancer strategies
– Of 8 screening strategies found most efficient, 6 of
them began at age 50
• Combining the increase in the number needed to
screen, the higher cost, and the marginal benefit
(from modeling studies), the USPSTF
recommended beginning screening at age 50
instead of age 40…..and then ducked for cover
Breast Examinations
• A 2009 literature review concluded that the
effectiveness of CBE has not been proven
• In addition, the CBE in community practice is
inferior to that in trials
– Trials typically have a standardized CBE which can take
up to 10 minutes to perform
• Standardized breast examinations may have a
small benefit, but at the expence of a large
amounts of false positives and time spend
performing the exam
Self Breast Examinations
• No studies have shown that regular self breast
examinations have any effect on prevention of
cancer diagnosis or mortality
– Significant increase in false positive findings
USPSTF (2009)
• Biennial screening mammography for women age 50 –
74 years
• Screening mammography before the age of 50 years
should be an individual one
• current evidence is insufficient for screening
mammography in women 75 years or older
• Insufficent evidence for clinical breast examination
(CBE) beyond screening mammography in women 40
years or older
• Not enough evidence to recommend digital or breast
MRI above and beyond mammography
• against teaching breast self-examination (BSE)
• Yearly mammograms are recommended starting
at age 40 and continuing for as long as a woman
is in good health
• Clinical breast exam (CBE) about every 3 years for
women in their 20s and 30s and every year for
women 40 and over
• Women should know how their breasts normally
look and feel and report any breast change
promptly to their health care provider. Breast
self-exam (BSE) is an option for women starting in
their 20s
• Women aged 40 to 49 years should have
screening mammography every 1 to 2 years
• Women aged 50 years and older should have
annual screening mammography
• All women should have clinical breast
examinations annually as part of the physical
• breast self-examination has the potential to
detect palpable breast cancer and can be
In Summary
• Concern over when to start screening
– 40 or 50 years old
• Concern over how frequently
– Every 1 or 2 years
– If beginning screening at age 40
• Cancers tend to grow at a faster rate in younger women
What I would Tell My Wife
• I would have her begin screening at age 40
• I would screen annually from 40 to 50
• I would screen biennially from 52 until her life
expectancy is less than 10 years
Colon Cancer Screening
• 146,000 new cases annually in the US
• Just under 50,000 die each year
• Incidence and mortality rates from CRC are
decreasing annually in the US
• Effect of screening may account for 53 percent
of the observed reduction in CRC mortality
Tests Used for Screening
• Divided into detection of early cancers and
removal of premalignant lesions
• Detection of early cancers (stool based tests)
– Guaiac-based fecal occult blood test (gFOBT)
– Fecal immunochemical test (FIT)
– Stool DNA panel
• Removal of premalignant lesions
Optical colonoscopy
Flexible sigmoidoscopy
Double contrast barium enema
CT colonography (virtual colonoscopy)
Fecal Occult Blood Test
• Multiple gFOBT trials have shown a 15 to 18 percent
mortality reduction from colon cancer
• FIT testing showed higher specificity than hemocult
SENSA and have at least the same sensitivity
– gFOBT may have higher sensitivity than FIT in higher grade
• Stool DNA testing
– More sensitive than gFOBT, both miss a lot of cancers that
were picked up on colonoscopy
– Have to collect entire bowel movement and ship it on ice
– Expensive
Flexible Sigmoidoscopy
• One time screening with flexible
– Between ages 55 and 64
– Incidence of CRC decreased by 23 percent
– Mortality from CRC decreased by 31 percent
Double Contrast Barium Enema
• Still requires bowel preparation
• False positives result from retained stool or
other causes of bowel irregularity
• Detects about half of adenomas greater than
1.0 cm
• Can miss up to 22 percent of colorectal
• Not commonly used as a screening procedure
Colonoscopy vs. Sigmoidoscopy
• Study looking at 1994 asymptomatic adults
– 5.7 percent had colon cancer
– 1.6 percent had proximal lesions only (lesions that wouldn’t be found
on a sigmoidoscopy)
• Higher risk of perforation in a colonoscopy
– Latest medicare numbers list the rate as 0.6 per 1,000 procedures
– 8.7 per 1,000 if a polypectomy was performed
• More expensive than sigmoidoscopy
• Patients with an abnormal sigmoidoscopy need to have a
• No randomized trials have been published on efficacy of
– Hey….the sigmoids work…why wouldn’t this?
2008 – The Debate
• Two societies released guidelines on how to
screen for colorectal cancer
• The ACS listed all of the above screening tests
as options
– Ranked the detection of premalignant lesions over
early cancers
– Did not recommend any of the modalities over
– Essentially, the ACS believes that the best cancer
prevention is the one that the patient will take
And then…
• The USPSTF releases their guidelines on
• Patients should be screening with:
– Colonoscopy every 10 years
– Sigmoidoscopy every 5 years, or
– FOBT with a sensitive test
USPSTF rankings
• Sensitivity
– Colonoscopy
– Hemoccult SENSA and flexible sigmoidoscopy
– FIT (a very close 3rd)
– Hemoccult II
• Specificity
– Colonoscopy and Flexible Sigmoidoscopy
– HemocultII and FIT
– Hemocult SENSA
• Recommends screening for colorectal cancer using fecal
occult blood testing (high sensitivity), sigmoidoscopy, or
colonoscopy, in adults, beginning at age 50 years and
continuing until age 75 years
• evidence is insufficient to assess the benefits and harms of
computed tomographic colonography and fecal DNA testing
as screening modalities for colorectal cancer
• recommends against routine screening for colorectal
cancer in adults age 76 to 85 years
– Some exeptions apply
• against screening for colorectal cancer in adults older than
age 85 years
• Beginning at age 50, both men and women
should follow one of these testing schedules:
Flexible sigmoidoscopy every 5 years
Colonoscopy every 10 years
Double-contrast barium enema every 5 years
CT colonography (virtual colonoscopy) every 5 years
Yearly fecal occult blood test (gFOBT)
Yearly fecal immunochemical test (FIT) every year
Stool DNA test (sDNA), interval uncertain
American College of Gastroenterology
• Colonoscopy every 10 years, beginning at age
• If unable to do this:
– Flexible sigmoidoscopy every 5 years
– computed tomography (CT) colonography every 5
– fecal immunochemical test (FIT)
What I Would Tell My Colon
• Begin screening at age 50 with a colonoscopy
and repeat every 10 years
In Summary
• Discuss the different methods of screening
– Discuss the difference of finding a cancer early vs.
finding a polyp that could become a cancer
• Given the superior sensitivity and selectivity
of the colonoscopy, this would likely be the
test to recommend
– If this is not done, then go down the line of the
different options
Prostate Cancer Screening
• 192,000 new cases diagnosed annually in the
– Most commonly diagnosed visceral cancer
• 27,000 deaths annually
• Lifetime risk of development is 16 percent
– Risk of dying from prostate cancer is 2.9 percent
Prostate Specific Antigen
• Originally introduced as a tumor marker to detect
– Also is elevated in BPH and prostatitis
• In the early 1990s, was adopted as a wide-spread
screening test
– There was no data testing the efficacy of PSA testing
• Dramatic increase in the diagnosis of prostate CA
– Incidence peaked in 1992
– Mortality from prostate cancer increased at the advent of
PSA screening, but has now declined to pre-PSA levels
• Attribution bias?
Problems with the PSA Test
• Most men with normal prostate numbers do not
have their prostates biopsied
– Overestimates sensitivity and underestimates
• Transrectal needle biopsy is not a gold standard
– False negative rate is 10-20 percent
• PSA cannot tell the difference between a bad
cancer or an indolent cancer
– Gleason score > 6 or volumes > 0.5 cm3 have greater
risk of progression
European Randomized Study of
Screening for Prostate Cancer (ERSPC)
• 182,160 men between 50 and 74 years old
• Multiple centers across multiple countries with
multiple different protocols
– Average interval was every 4 years
• PSA cutoff was 3.0 (in most centers)
• The PSA screening rate in the control group was not
• Mortality from prostate cancer was 20 percent lower in
the study group
– NNS 1410 men to prevent one cancer death over 9 years
– 48 additional cases of prostate cancer needed to be
treated to prevent one death of prostate cancer
Bias Towards the Null Hypothesis
• Substantial portion of the control group
received screening
• 25% of cancers detected in the screening
group did not receive treatment
• Given substantial lead time of prostate cancer,
the follow up period may have been
Bias Away for the Null Hypothesis
• Cancers detected in the screening group were
treated more aggressively that the control
– May have had better treatments
United State Prostate, Lung, Colorectal and
Ovarian Cancer (PLCO) Screening Trial
• 76,693 men between ages 55 and 74 assigned
to annual screening
• After seven years of follow up, no reduction in
prostate cancer mortality
– Again, not a very long follow up
• Screening in the control group was 52 percent
– Cancer detection in the screening group was
higher than in the control group
Problems with Both Studies
• Control groups had a high percentage of PSA
• Study time may not have been long enough to
effectively assess the benefits of PSA
Prostate Cancer Prevention Trial
• Gives insight on how imperfect PSA is
• 449 of 2950 men (15.2 percent) ages 62 to 91
years and consistently normal PSA had prostate
– 2.3 percent had high-grade cancer
• Among men with PSA concentration between 2.1
and 4.0, 24.7 percent had prostate cancer
– 5.2 percent had Gleason score of 7 or greater
• Even a PSA cutoff of 1.1 missed 17 percent of
Harms from Screening
• Risk of biopsy
– Anxiety over the possibility of diagnosing cancer
– Often does not go away due to the higher false
negative rate
• Overdiagnosis
– Lifetime risk of being diagnosed with prostate cancer
has increased from 1 in 11 to 1 in 6
– Risk of dying from prostate cancer has remained at 1
in 34
– Estimates of overdiagnosis from modeling studies
range from 23 to 42 percent
• Used data from the ERSPC trial
Risks of Therapy
• Radical Prostatectomy
– 0.5% mortality rate
– 45% decrease in sexual function (range 20 – 70%)
– 33% in urinary incontinence (range 15 – 50%)
• External beam radiation
– 32% decrease in sexual function (range 20-45%)
– 8% urinary incontinence (range 2-16%)
– 21% in bowel dysfunction (range 6-25%)
• current evidence is insufficient for prostate
cancer screening in men younger than age 75
• against screening for prostate cancer in men
age 75 years or older
• recommends that men make an informed
decision with their doctor about whether to
be tested for prostate cancer
American Urological Association
• the age for obtaining a baseline PSA has been lowered
to 40 years
• no longer recommends a single, threshold value of PSA
free and total PSA
patient age
PSA velocity
PSA density
family history
prior biopsy history
Talking Points with Patients
• Prostate cancer is an important health problem; it is one of the most
frequently diagnosed cancers in the US and one of the leading causes of
cancer deaths in men
• The patient needs to be involved in the decision
• Screening may reduce the risk of dying from prostate cancer.
– Evidence is mixed
– Benefit is small
Screening is associated with a significant risk of being overdiagnosed
The screening tests that are currently in use may miss a cancer
PSA (with or without DRE) can detect cancers at a earlier stage
Aggressive therapy is necessary to realize any benefit from screening
Surgery and radiation are most common, but they have a risk of sexual
dysfunction and urinary incontinence
• Most men with prostate cancer die from other causes
– Our tests can’t tell the difference between aggressive and indolent cnacers
What is the correct answer?
• Need for a better test
– Lead time is 6.9 years and over diagnosis of
prostate cancer is estimated at 42%
• Type of test needed…
– Not just something to differentiate between
BPH/prostatis and prostate cancer
– We need something that will differentiate
aggressive prostate cancer vs. indolent prostate
What I Would Tell My Prostate
• I would begin screening at age 50
• I am going to request screening every 4 years
• If I have an elevated PSA, I would like active
surveillance and keep many other factors in
mind when deciding diagnosis (current health
problems, absolute PSA level and level of rise,
as well as symptoms)
• I would continue DRE annually
In Summary
• Unfortunately, the discussion about screening
is not cut and dry
• Our patients deserve to know what they are
getting into when we recommend screening
• Often times, the epidemiology and the
population numbers don’t matter when
dealing with a one on one situation
– Think of what advice you would give your loved
Conversation with Patients
• Take into account the patient personality
– Diagnose and treat at all costs vs. diagnose and treat
when the numbers tell us to
– Have a detailed conversation with this patient
• Information sheets
• Group information sessions
• Individual discussions
• Take into account you own beliefs about the data
– Too much data out there to present in one
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