© 2015 American College of Physicians The information contained herein should never be used as a substitute for clinical judgment.

A 60-year old woman who is contemplating lung cancer screening November 6, 2014 Richard M. Schwartzstein, MD Phillip M. Boiselle, MD Gerald W. Smetana, MD Deborah Cotton, MD, MPH

THE GUIDELINE: Recommends annual low-dose chest CT screening 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 (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 NEJM 2011;365:395

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%

LUNG CANCER: Incidence and Mortality by Study Year

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 She has Gold class II COPD 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 Hypertension Type 2 diabetes Chronic kidney disease 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 Lives with her husband and son Human services worker 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 Albuterol MDI Gabapentin Fluticasone MDI Glipizide Current Medications Albuterol MDI Gabapentin Fluticasone MDI Glipizide Ipratropium / albuterol MDI Losartan Metformin Atenolol Trazodone Atorvastatin Warfarin Bupropion Diazepam Clopidogrel

OUR PATIENT Well appearing Bp 115/62, HR 83, Weight 178#, BMI 31 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 Do you think that CT screening for lung cancer adds value and in which subsets of patients? 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? 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? 12k U.S. Lung Cancer Deaths per year DC: Hard to interpret this slide….you need to put titles on x and y axes LW: I created the axes, but let me know if you want changes made. He said: “If we think very broadly, it’s been estimated that if CT screening for lung cancer was applied to population in the US that meets screening guidelines, we’d save somewhere between 12,000 and 20,000 deaths from lung cancer each year.” 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 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 Study Sensitivity Specificity PPV NPV NLST 71.1% 62.7% 3.4% 99.2% PLCOm2012 83.0% 62.9% 4.0% 99.5% What is “PLCO m2012” can’t figure out this acronym Prostate, Lung, Colorectal, and Ovarian (PCLO) Cancer Screening Trial, 2012 Model *Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 2012 Model Tammemägi et al NEJM 2013; 368(8):728-36

PERSONALIZED RISK FOR MS D DC: Looks ok, hard to read the small print. LW: I made it as large as I could. He goes over this so briefly that I wouldn’t be too worried about it for the video. 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 DC: I don’t think you mean “competing medical causes”. Perhaps” competing medical problems” or” “competing medical risks” ? LW: Which of Deb’s suggestions do you prefer?

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)

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 Compared to US Census, NLST: 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 DC: Might be more clear if you say She differs from most NLST participants” LW: Done.

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 DC: “participating” should be “participates” LW: I think it is correct, especially with attention to the way in which he discusses it. Perhaps it could be rephrased for clarity? He says: “I think that for her and for other patients this really begins with a commitment to participating in a shared decision making process…”

UNDERSTANDING RISKS AND BENEFITS 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 DC: “mos”is confusing…write out “months” or make the “s” smaller than the “mo” LW: Done.

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. 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 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

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? DC: Poll Title: Would you recommend lung CT screening for cancer for Ms. D? LW: Done.

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.?

Beyond the Guidelines Editors We would like to thank… Our Patient Discussants Phillip Boiselle, MD Richard Schwartzstein, MD Beyond the Guidelines Editors Risa Burns, MD, MPH Eileen Reynolds, MD Deborah Cotton, MD, MPH Gerald Smetana, MD Video Production Last Minute Productions

BIDMC Media Services Series Coordinator 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.