© 2015 American College of Physicians
The information contained herein should never be
used as a substitute for clinical judgment.
BEYOND THE GUIDELINES:
A 60-year old woman who is contemplating lung cancer
screening
Medicine Grand Rounds
November 6, 2014
Discussants
Richard M.
Schwartzstein, MD
BI Section Editor
Gerald W.
Smetana, MD
Phillip M. Boiselle, MD
The Series Editors have no conflicts of interest to disclose.
Moderator
Deborah Cotton,
MD, MPH
THE GUIDELINE:
USPSTF Recommendation Statement on Screening for
Lung Cancer
• Recommends annual low-dose chest CT screening
• Adults age 55-80
• ≥ 30 pack-year history of smoking
• Currently smoking or quit in past 15 years
•
Stop screening if no cigarettes > 15 years or major
medical comorbidity
*Moyer VA, on behalf of the U.S. Preventive Services Task Force. Screening for Lung Cancer: U.S. Preventive Services Task Force
Recommendation Statement. Ann Intern Med. 2014;160:330-338. doi:10.7326/M13-2771
BACKGROUND
• Lung cancer is the leading cause of
cancer death in the U.S.
• 85% of cases are diagnosed at a late stage with
regional LN or distant metastases
• 5-year overall survival rate 17%
• Studies of screening with plain CXR have not
shown reduced lung CA mortality
NATIONAL LUNG SCREENING TRIAL
(NLST)
•
•
•
•
N=53,453
Aged 55-74
30 pack years, smoked within 15 years
Random assignment to:
- Low dose CT annually x 3 years
- Or single plain CXR
• Outcome all cause and lung cancer specific
mortality
• Median f/u 6.5 years
*The National Lung Screening Trial Research Team Reduced Lung-Cancer Mortality with Low-Dose Computed
Tomographic Screening N Engl J Med 2011; 365:395-409
NLST: RESULTS
Single
CXR
Annual
LDCT x3
RRR
95% CI
Rate of positive test
6.9%
24.4%
% of positive tests that
were false positive
94.5%
96.4%
Lung cancer incidence/
100,000
572
645
Lung cancer death /
100,000
309
247
20.0%
6.8-26.7%
Death any cause
/100,000
1389
1303
6.7%
1.2-13.6%
*The National Lung Screening Trial Research Team Reduced Lung-Cancer Mortality with Low-Dose Computed
Tomographic Screening N Engl J Med 2011; 365:395-409
LUNG CANCER:
Incidence and Mortality by Study Year
*Reproduced with permission from:
The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality
with Low-Dose Computed Tomographic Screening N Engl J Med 2011; 365:395-409.
© Massachusetts Medical Society
OUR PATIENT
Medical History
• Ms. D began smoking at age 13. She has
averaged 1 pack per day since (47 pack years)
• Tried bupropion, varenicline, nicotine
replacement with no benefit
• She stopped smoking 2 months ago when
threatened with loss of a leg due to an arterial
occlusion
OUR PATIENT
Medical History (cont.)
• She has Gold class II COPD
• Chronic productive cough and DOE
• Hospitalized 4 months ago for a COPD
exacerbation
• Recent spirometry showed FEV1 1.49 (58%
predicted), FVC 2.64 (79% predicted),
FEV1/FVC 56%
OUR PATIENT
Past Medical History
•
•
•
•
•
•
•
•
Hypertension
Type 2 diabetes
Chronic kidney disease
Sciatica
s/p carotid endarterectomy
Coronary artery disease, s/p PCI
Anxiety & depression
Elevated cholesterol
OUR PATIENT
Social History
• Lives with her husband and son
• Human services worker
• Works with mentally ill adults
• On disability for 2 months since embolus to
leg
OUR PATIENT
Current Medications
• Albuterol MDI
• Fluticasone MDI
• Ipratropium / albuterol
MDI
• Atenolol
• Atorvastatin
• Bupropion
• Clopidogrel
•
•
•
•
•
•
•
Gabapentin
Glipizide
Losartan
Metformin
Trazodone
Warfarin
Diazepam
OUR PATIENT
Physical Examination
• Well appearing
• Bp 115/62, HR 83, Weight 178#, BMI 31
• Chest – end expiratory rhonchi
• Cardiac – normal S1S2, no murmur
• Extremities – no clubbing or edema. Feet warm
with normal capillary refill. DP/PT pulses not
palpable
OUR PATIENT
Chest Radiograph
MS D’S STORY
QUESTIONS
For Dr. Schwartzstein and Dr. Boiselle
1. Do you think that CT screening for lung cancer adds
value and in which subsets of patients?
2. Do you feel that one can generalize the results of
the NLST to radiology departments outside of large
academic centers and to diverse populations that
may differ from those in the trial?
3. How can doctors assist patients in dealing with the
uncertainties associated with lung cancer screening?
OUR MODERATOR & DISCUSSANTS
• Deborah Cotton, MD, MPH (Moderator)
Professor of Medicine, Boston Univ. School of Medicine
Deputy Editor, Annals of Internal Medicine
• Phillip M. Boiselle, MD
Professor of Radiology, HMS
Department of Radiology, BIDMC
• Richard M. Schwartzstein MD
Professor of Medicine, HMS
Pulmonary and Critical Care, BIDMC
CONFLICT OF INTEREST DISCLOSURE
The speakers have no financial relationships
with a commercial entity producing
healthcare-related products and/or services.
Deborah Cotton, MD, MPH
Phillip Boiselle, MD
Richard Schwartzstein, MD
Dr. Boiselle
Radiology Viewpoint
I. DOES CT SCREENING ADD VALUE?
180
U.S. Lung Cancer Deaths per year
160
12k
140
120
100
80
60
40
20
0
No Screen
Screen
Patients screened versus not screened
HIGHER RISK = HIGHER POTENTIAL BENEFIT
Highest Quintile NLST:
• 60-fold greater
number of prevented
lung cancer deaths
• Fewer false-positive
results per screenprevented cancer (65
vs 1648, P<0.0001)
• Smaller # needed to
screen (5276 vs 161)
Reproduced with permission from: Kovalchik SA, et al. Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer
Death. N Engl J Med 2013; 369:245-254. © Massachusetts Medical Society
PERSONALIZED APPROACH
• PLCOm2012* personalized risk model
• Smoking history, age, BMI, ethnicity, lung ca
history, COPD, ILD, education level
• More efficient than NLST criteria at
identifying persons for CT screening
Study
NLST
PLCOm2012
Sensitivity
71.1%
83.0%
Specificity
62.7%
62.9%
*Andriole GL, et al. Prostate Cancer Screening in the Randomized Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after
13 Years of Follow-up JNCI J Natl Cancer Inst 2012; 104 (2): 125-132.
PPV
3.4%
4.0%
NPV
99.2%
99.5%
*Tammemägi MC, et al. Selection Criteria for Lung-Cancer
Screening. N Engl J Med 2013; 368:728-736.
PERSONALIZED RISK FOR MS D
*Tammemägi MC, et al. Selection Criteria for Lung-Cancer Screening. N Engl J Med 2013; 368:728-736.
MS D’S RISK CALCULATION
2.9%
Highest Risk
COMPARISON LOWER RISK PATIENT
Low Risk
HOW DO WE DEFINE VALUE
• Value of LDCT
screening is likely
determined primarily
by the risk of lung
cancer compared to
the competing causes
of death for an
individual patient
*Bach PB, Mirkin JN, Oliver TK, et al. Benefits and Harms of CT
Screening for Lung Cancer: A Systematic Review. JAMA.
2012;307(22):2418-2429.
VALUE FOR MS D IS UNCERTAIN
• We know she is at high risk
for lung cancer
AND
• We need to learn more
about her competing
medical comorbidities and
potential likelihood of
surviving lung ca surgery
II. CAN WE GENERALIZE NLST RESULTS?
• Nearly 25% of participating
NLST sites were not tertiary
care AMCs
• International Early Lung
Cancer Action Program
demonstrated successful
application of prescribed
screening regimen across
diverse practice settings
ENSURING UNIFORM QUALITY
ACR Quality Initiatives
• Practice Parameters
• Lung-RADS reporting/data
• Site Accreditation
ACCP and ATS Policy Statement for High Quality
Screening
• Organized quality program and USPSTF selection
criteria will ensure that screening benefits outweigh
harms
LUNG-RADS
• Increased size threshold of positive screen to 6 mm
• 9 of 10 participants will require no further imaging between
annual CT scans
• Confirmed in clinical LDCT program (Lahey, n=2180)
Reprinted with permission from the American College of Radiology. No other representation of this material is authorized without
the expressed, written permission from the ACR. Refer to the Lung Imaging Reporting and Data System
(Lung-RADS) at http://www.acr.org/Quality-Safety/Resources/LungRADS for the most current information.
ENSURING UNIFORM QUALITY OF CARE
• Multidisciplinary approach
–
–
–
–
–
Radiology
Pulmonary Medicine
Pathology
Thoracic Surgery
Medical and Radiation Oncology
• Surgical mortality rates directly
influence success of screening
outcomes
DIVERSE POPULATIONS
• 53,454 participants
– 41% women
– 10% minority enrollment
• Compared to US Census, NLST:
– Younger
– Higher education
– More likely former smokers
• Able to undergo curative surgery
• No comorbid conditions that
would pose a substantial risk of
death in the next 8 yrs
HOW ABOUT MS D?
• Consensus that NLST results can
be generalized to patients who
meet study criteria and are in
“reasonably good health”
• Ms. D meets NLST entry criteria
• She differs from most NLST
participants due to her general
health status and uncertain
candidacy for lung cancer surgery
USPSTF
• “Screening may not be
appropriate for patients with
substantial comorbid
conditions, particularly those
at the upper end of the
screening age range”
• Age range = 55-80
55
60
65
70
75
80
III. DEALING WITH UNCERTAINTY
• Assisting patients begins
with a commitment to
participating in a shared
decision making process
that carefully considers
the scientific evidence for
CT screening as well as a
patient’s values and
preferences
UNDERSTANDING RISKS AND BENEFITS
RISKS
• False-positive results
• Anxiety
• Potential for
unnecessary testing
• Radiation exposure
• Financial costs
• Over-diagnosis
ANXIETY
• No measurable increase in anxiety
or decrease in health related QOL
at 1 or 6 months among NLST pts
with false-positives (n=1024)
• Attributed to detailed consent
*Gareen IF, et al. Impact of lung cancer screening results on participant
health-related quality of life and state anxiety in the National Lung Screening
Trial. Cancer 2014; 120: 3401-3409.
• Ms. D is at high risk given her
history of anxiety and concerns
about watchful waiting
SCREENING CONVERSATION WITH MS D
• Likelihood of a positive
screening result
• High percentage of positive
results that prove to be falsepositive
• Importance of following
evidence-based nodule
management
recommendations, including
“watchful waiting”
ONGOING SCREENING CONVERSATIONS
• Should Ms D and her physician
decide that CT screening is
appropriate at this time, these
topics need to be revisited in
the event of a positive result
• Annual reassessments of her
risk-benefit ratio, especially
competing medical conditions
and potential likelihood of
surviving lung cancer surgery
SUMMARY
• Personalized risk profile helps determine an
individual’s potential benefits and risks
• Value of LDCT screening is likely determined
primarily by the risk of lung cancer compared to the
competing causes of death for an individual patient
• Shared decision making process carefully considers
the scientific evidence for CT screening and a
patient’s values and preferences
• A decision to undergo or forego LDCT screening
should be an informed and shared one
Dr. Schwartzstein
Primary Care Viewpoint
SCREENING AND THE POPULATION
PERSPECTIVE
• What is good for
300 million
people?
• Small changes in
relative risk may
lead to significant
lives saved for a
population
SCREENING AND THE INDIVIDUAL
• What is good for a
single person?
• Relative risk tells only
part of the story. What
is the absolute risk for
this patient given her
particular story?
• Absolute risk of dying
from lung cancer in
NLST only 1.7%.
Screening reduced risk
to 1.4%.
RISK FACTORS BEYOND SMOKING
Additional risk factors
• Family history
• Presence of
emphysema
• Occupational exposures
• Interstitial lung disease
• Exposure to radon
This patient:
• Has obstructive lung
disease
• Not clear if emphysema
also present. Story
suggestive of chronic
bronchitis.
• No other risk factors
evident.
NLST – WHO WAS REALLY AT RISK
• Vast majority of cancer deaths were in the half
of the group with the highest risk
• Would have to screen 5,000 patients to
prevent one cancer death in the lower risk
patients in the NLST, compared to screening
161 patients to save one death in highest risk
group
*Kovalchik SA, et al. Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death.
N Engl J Med 2013; 369:245-254.
DIFFERENTIAL RISK WITHIN NLST
*Bach PB, Gould MK. When the Average Applies to No One: Personalized Decision Making About Potential Benefits of
Lung Cancer Screening. Ann Intern Med. 2012;157:571-573.
VALUE ADDED CARE
• How does the intervention add
value to the life of the patient?
Not just cost issues.
• Consider:
– Quality of life, what is
important to the patient?
– False positives?
– Complications from
evaluation (biopsies;
surgery)?
– Emotional burden: How well
can she deal with
uncertainty?
• Calculations in NLST re:
complications
– predicated on following the
protocol, e.g., following small
nodules with repeat CT scans
– Not clear emotional issues re:
uncertainty were addressed
OUR PATIENT
• She fits the general criteria defined by NLST
• Smoking risk, but not apparent additional risk
factors for lung ca
• Increased risk for surgical interventions based
on lung disease, poor functional/exercise
status, and underlying vascular disease; would
like to know diffusing capacity
OUR PATIENT’S VALUES
• “Leave well enough alone”
• Would not want to wait for follow-up scans if
small nodule found; “I would want it out!”
• Given high rate of false positives in study, her
anxiety/values places her at increased risk of
an unnecessary surgery and its complications
• Does not really understand the concept of
screening and the pathobiology of lung cancer.
Could we make her understand?
SUMMARY
• Screening appropriate for
– high risk patients with
appropriate
understanding of
screening principles,
– ability to tolerate high
false positive rate
– desire to undergo
radiation and possible
unnecessary surgery
for small absolute risk
reduction of dying
from lung cancer
• Academic centers favored
for patients with comorbidities that may
required greater multidisciplinary attention
• Patients must be able to
accept watching small
nodules with follow-up
scans; issues of dealing
with uncertainty
addressed before entry
into screening
Dr. Boiselle and Dr. Schwartzstein:
A Discussion
EDITOR’S SUMMARY
AGREEMENT: STRATIFY RISK
• Absolute vs. relative risk reduction
• Not all patients who are screened gain equally in
terms of reduced mortality
• Need to further stratify risk estimate beyond the
broad inclusion criteria in NLST and USPSTF
• Screening of greatest value in highest risk patients
(age, number of pack-years, COPD, other factors)
• Online tools exist to stratify lung CA risk
AGREEMENT – SCREENING
PROVIDES LOW ADDED VALUE IF:
• Severe competing comorbidities
• Short expected lifespan
• Cardiopulmonary contraindications to lung
resection if suspicious nodule found
• Patient is unable to tolerate uncertainty
during the prolonged periods between CT
studies
Shared Decision Making
WE CAN AGREE TO DISAGREE
• How common is anxiety among patients who
opt for screening?
• Do the NLST results apply to non-academic
and community hospital settings?
• Neither discussant considered:
– Cost to patient or society
– Threat of CT screening as a tool to encourage
cigarette cessation
Would you recommend lung CT
screening for cancer for Ms. D?
DR. MARK ZEIDEL
What are the Canadian and European
guidelines for lung cancer screening, and
how are they approaching these decisions
to screen?
DR. THOMAS DELBANCO
How can we have these complex
discussions with patients in the office and
help them to remember the most
important issues to consider?
DR. WILLIAM TAYLOR
Can you comment on the risk of
overdiagnosis: cancers that may be
detected that won't cause trouble during a
patient' lifetime?
DR. ADNAN MAJID
Can you comment on the relative efficacy
of screening in lung cancer related to the
current discussion about screenings for
colon cancer and breast cancer, etc.?
We would like to thank…
Our Patient
Discussants
Phillip Boiselle, MD
Richard Schwartzstein, MD
Beyond the Guidelines Editors
Risa Burns, MD, MPH
Deborah Cotton, MD, MPH
Eileen Reynolds, MD
Gerald Smetana, MD
Video Production
Last Minute Productions
We would like to thank…
BIDMC Media Services
Series Coordinator
Lizzie Williamson
© 2015 American College of Physicians
The information contained herein should never be
used as a substitute for clinical judgment.