1. © 2015 American College of Physicians
The information contained herein should never be used as a substitute for clinical judgment.

2. 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

3. 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 ;160:330

4. 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

5. 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

6. 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% %
Death any cause /100,000
1389
1303
6.7% %

7. LUNG CANCER:
Incidence and Mortality by Study Year

8. 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

9. 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 FEV (58% predicted), FVC 2.64 (79% predicted), FEV1/FVC 56%

10. 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

11. 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

12. 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

13. 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

14. OUR PATIENT
Chest Radiograph

15. MS D’S STORY

16. 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?

17. 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

18. 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

19. Dr. Boiselle Radiology Viewpoint

20. 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

21. 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:

22. 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

23. 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

24. MS D’S RISK CALCULATION
2.9%
Highest Risk

25. COMPARISON LOWER RISK PATIENT
Low Risk

26. 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):

27. 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?

28. 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

29. 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

30. 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)

31. 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

32. 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

33. 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.

34. 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

35. 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…”

36. UNDERSTANDING RISKS AND BENEFITS
False-positive results
Anxiety
Potential for unnecessary testing
Radiation exposure
Financial costs
Over-diagnosis

37. 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:
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.

38. 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”

39. 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

40. 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

41. Dr. Schwartzstein Primary Care Viewpoint

42. 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

43. 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%.

44. 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.

45. 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

46. DIFFERENTIAL RISK WITHIN NLST
Bach et al. Ann Intern Med. 2012

47. 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

48. 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

49. 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?

50. 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

51. Dr. Boiselle and Dr. Schwartzstein: A Discussion

52. 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

53. 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

54. Shared Decision Making

55. 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

56. 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.

57. DR. MARK ZEIDEL
What are the Canadian and European guidelines for lung cancer screening, and how are they approaching these decisions to screen?

58. 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?

59. 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?

60. 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.?

61. 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

62. BIDMC Media Services Series Coordinator
We would like to thank…
BIDMC Media Services
Series Coordinator
Lizzie Williamson

63. © 2015 American College of Physicians
The information contained herein should never be used as a substitute for clinical judgment.