© 2015 American College of Physicians

The information contained herein should never be used as a substitute for clinical judgment.

Discussants BI Section Editor Moderator

BEYOND THE GUIDELINES:

Medicine Grand Rounds

Richard M. Schwartzstein, MD

Phillip M. Boiselle, MD

Gerald W. Smetana, MD

Deborah Cotton, MD, MPH

A 60-year old woman who is contemplating lung cancer screening

November 6, 2014

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

Ann Intern Med, March 14 2014;160:330

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

• 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

(NLST)

NEJM 2011;365:395

NLST: RESULTSSingle 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%

LUNG CANCER:Incidence and Mortality by Study Year

OUR PATIENTMedical 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 PATIENTMedical 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 PATIENTPast 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 PATIENTSocial 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 PATIENTCurrent Medications

• Albuterol MDI• Fluticasone MDI• Ipratropium / albuterol

MDI• Atenolol• Atorvastatin• Bupropion• Clopidogrel

• Gabapentin• Glipizide• Losartan• Metformin• Trazodone• Warfarin• Diazepam

OUR PATIENTPhysical 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 PATIENTChest Radiograph

MS D’S STORY

QUESTIONSFor 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 MedicineDeputy Editor, Annals of Internal Medicine

• Phillip M. Boiselle, MDProfessor of Radiology, HMSDepartment of Radiology, BIDMC

• Richard M. Schwartzstein MD Professor of Medicine, HMSPulmonary 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, MPHPhillip Boiselle, MDRichard Schwartzstein, MD

Dr. BoiselleRadiology Viewpoint

I . DOES CT SCREENING ADD VALUE?

No Screen Screen0

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Chart Title

12k

Patients screened versus not screened

U.S

. Lun

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per y

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HIGHER RISK = HIGHER POTENTIAL BENEFIT

Highest Quintile NLST: • 60-fold greater

number of prevented lung cancer deaths

• Fewer false-positive results per screen-prevented cancer (65 vs 1648, P<0.0001)

• Smaller # needed to screen (5276 vs 161) Kovalchik et al NEJM 2013; 369:245-254

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

Tammemägi et al NEJM 2013; 368(8):728-36

Study Sensitivity Specificity PPV NPVNLST 71.1% 62.7% 3.4% 99.2%PLCOm2012 83.0% 62.9% 4.0% 99.5%

*Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 2012 Model

PERSONALIZED RISK FOR MS D

Tammemägi et al NEJM 2013; 368(8):728-36

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 et al 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

I I . 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 QUALITYACR Quality Initiatives• Practice Parameters• Lung-RADS reporting/data• Site AccreditationACCP 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)

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 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 false-positive

• 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. SchwartzsteinPrimary 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 et al. NEJM 2013

DIFFERENTIAL RISK WITHIN NLST

Bach et al. Ann Intern Med. 2012

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 co-morbidities that may required greater multi-disciplinary 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

E D I TO R ’ S S U M M A RYAG R E E M E N T: ST R AT I F Y R I S K

• 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 PatientDiscussants

Phillip Boiselle, MDRichard Schwartzstein, MD

Beyond the Guidelines EditorsRisa Burns, MD, MPH Eileen Reynolds, MDDeborah Cotton, MD, MPH Gerald Smetana, MD

Video ProductionLast Minute Productions

We would like to thank…

BIDMC Media Services

Series CoordinatorLizzie Williamson

© 2015 American College of Physicians

The information contained herein should never be used as a substitute for clinical judgment.