LUNG CANCER SCREENING: ON WHOM DID YOU DO IT AND ON WHOM DO YOU RESPOND TO THE RESULTS?

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1 LUNG CANCER SCREENING: ON WHOM DID YOU DO IT AND ON WHOM DO YOU RESPOND TO THE RESULTS? DAVID O. WILSON, MD, MHP DIRECTOR GEORGIA COOPER MEMORIAL LUNG CANCER RESEARCH REGISTRY UNIVERSITY OF PITTSBURGH MEDICAL CENTER PITTSBURGH, PA Dr. David Wilson is a long time faculty member in the Division of Pulmonary, Allergy & Critical Care Medicine. He is the founding Director of the Pittsburgh Lung Screening Study (PLuSS), the largest single institution observational study of low dose CT screening for lung cancer, since He is the co-founder and co -Director of the Lung Cancer Multidisciplinary Clinic and Lung Cancer Center at the Hillman Cancer Center of the University of Pittsburgh Cancer Institute (UPCI). He is the Director of the Georgia Cooper Memorial Lung Cancer Research Registry at the University of Pittsburgh. In addition, he sees patients every day, focusing on lung nodules, lung cancer and directs the pulmonary clinic at the Hillman Cancer Center. He introduced endobronchial ultrasound and electronavigational bronchoscopy to Pittsburgh in 2007 and has written extensively about EBUS, lung cancer screening and the relationship between COPD and lung cancer. He is funded by the NIH, NCI and UPCI. Along with his wife Amanda, he has 5 children ages 21-28, and is just now learning what to do with the free time he never had before. OBJECTIVES: Participants should be better able to: 1. Understand who is eligible for lung cancer screening; 2. Understand the risks and benefits of low dose CT scans to allow informed and shared decision making with patients; 3. Learn the basics of a lung cancer screening program. FRIDAY, MARCH 13, :00AM 1

2 Lung Cancer Screening: On Whom Do You Do It and On Whom Do You Respond To The Results? David O. Wilson MD, MPH NAMDRC March 2015 DISCLOSURE Dr. Wilson has received research grants from NIH and NCI, but these do not create a conflict related to the following presentation. 2

3 LDCT Advocates NCCN Nov 2011 ( IASLC Jan 2012 (JTO) ASCO/ACCP May 2012 (JAMA) AATS - July 2012 (JTCVS ) USPSTF - August 2013 (AIM) Medicare (MEDECAC) Dec Adults USPSTF 2013 > 30 pack year smoking history Smoked within past 15 years Grade B = insurance companies are required to cover without co-pay or deductible (ACA) Annals of Int Med

4 Remarks 1) Include counseling of potential benefits & harms 2) Conduct screening at similar centers to NLST multidisciplinary coordinated care (centers of excellence) 3) Incorporate quality metrics 4) Screening is not a substitute for smoking cessation Bach et al JAMA 2012;307: Question 1: Why do we care about LDCT lung cancer screening? A) Lung cancer is the # 1 cause of cancer death in the U. S. B) LDCT has been proven to reduce lung cancer deaths in the U. S. C) It has helped put Dr. Wilson s kids through college D) All of the above 4

5 Question 1 Why do we care about LDCT lung cancer screening? A. Lung cancer is the # 1 cause of cancer death in the U. S. B. LDCT has been proven to reduce lung cancer deaths in the U. S. C. It has helped put Dr. Wilson s kids through college D. All of the above A. 0% 0% 0% 0% B. C. D. CMS LDCT SCREENING REQUIREMENTS (2015) Age years; Asymptomatic (no signs or symptoms of lung disease, no history of lung cancer); Tobacco smoking history of at least 30 pack-years Current smoker or one who has quit smoking within the last 15 years; and 5

6 CMS LDCT SCREENING REQUIREMENTS (2015) For the initial LDCT lung cancer screening service: the beneficiary must receive a written order for LDCT lung cancer screening during a unique lung cancer screening counseling and shared decision making visit, For subsequent LDCT lung cancer screenings: the beneficiary must receive a written order, which may be furnished during any appropriate visit (for example: during the Medicare annual wellness visit, tobacco cessation counseling services, or evaluation and management visit) CMS LDCT SCREENING REQUIREMENTS A lung cancer screening counseling and shared decision making visit includes the following elements (and is appropriately documented in the beneficiary s medical records): 1) Determination of beneficiary eligibility including age, absence of signs or symptoms of lung disease, a specific calculation of cigarette smoking pack-years; and if a former smoker, the number of years since quitting; 2) Shared decision making, including the use of one or more decision aids, to include benefits, harms, follow-up diagnostic testing, over-diagnosis, false positive rate, and total radiation exposure; 3) Counseling on a) the importance of adherence to annual LDCT lung cancer screening, impact of comorbidities and ability or willingness to undergo diagnosis and treatment and b) the importance of maintaining cigarette smoking abstinence if former smoker, or smoking cessation if current smoker. 6

7 CMS LDCT SCREENING REQUIREMENTS Written orders for both initial and subsequent LDCT lung cancer screenings must contain the following information, which must also be documented in the beneficiaries medical records: Beneficiary date of birth, Actual pack-year smoking history (number); Current smoking status, and for former smokers, the number of years since quitting smoking; Statement that the beneficiary is asymptomatic; and NPI of the ordering practitioner. Question 2: All of the following patients are eligible for LDCT except: A) 62 year old retired insulation worker, 30 pack year smoker who quit 12 years ago B) 58 old female 20 pack a day smoker whose mother & 2 siblings died of lung cancer C) 70 year old veteran 2 pack per day smoker D) 60 year old 40 pack year smoker who quit 10 years ago 7

8 Question 2 All of the following patients are eligible for LDCT except: A. 62 year old retired insulation worker, 30 pack year smoker who quit 12 years ago B. 58 old female 20 pack a day smoker whose mother & 2 siblings died of lung cancer C. 70 year old veteran 2 pack per day smoker D. 60 year old 40 pack year smoker who quit 10 years ago 0% 0% 0% 0% A. B. C. D. 8

9 SURVIVAL STRATIFIED by TUMOR SIZE Patz, Chest 2000 T Re-staging 2010 T1 = T1a (< 2 cm) + T1b (> 2 & < 3 cm) = stage IA T2 = T2a (> 3 & < 5 cm) stage IB T2b (> 5 & < 7 cm) stage IIA T2c ( > 7 cm) T3 stage IIB 9

10 In 1992, ELCAP (Early Lung Cancer Action Program) was born. ELCAP, now I-ELCAP, quickly attracted other institutions. Among the findings: Curability of Stage I lung cancers is 80-90% Annual CT screening allows at least 80% of lung cancers to be diagnosed at Stage I CT screening creates a counseling opportunity that results in greater smoking cessation Costs of CT screening for lung cancer compare favorably with breast, cervical, and colon cancer screenings Henschke CI, et al. Early Lung Cancer Action Project: Overall Design and Findings From Baseline Screening. The Lancet 1999; 354: CT as a SCREENING TOOL Most sensitive imaging modality for detecting pulmonary nodules Single breath hold low dose fast spiral CT = conventional CT High rate of nodules detected = vast numbers of false (+) scans Does CT detection of smaller nodules/cancers improve mortality from lung cancer? (intuitive but unproven until NLST) 10

11 N L S T National Lung Screening Trial National Cancer Institute NEJM 2011;356: NLST DESIGN ARMS Helical CT v. CXR Difference in lung cancer specific mortality 20 % Power 90 % Compliance Contamination Size 85 %CT/80 % CXR 5 % CT/10 % CXR 25,000 each arm 11

12 NLST by the Numbers 53,464 participants (accrued n 18 months) 148,011 participant exams Male 31,545 (59 %) Female 21,919 Age : < 60 22,872 (43 %) ,887 (48 %) > 70 4,705 (8 %) 33 sites in 28 US states Results of Interim Analysis of Primary Endpoint Reported on Oct. 20, 2010 Arm Person years (py) Lung cancer deaths Lung cancer mortality per 100,000 py Reduction in lung cancer mortality Value of test statistic Efficacy boundary CT 144, CXR 143, Deficit of lung cancer deaths in CT arm exceeds that expected by chance, even allowing for multiple looks at the data. 12

13 Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer. The National Lung Screening Trial Research Team. N Engl J Med 2011;365: Cancer statistics, 2015 CA: A Cancer Journal for Clinicians Volume 65, Issue 1, pages 5-29, 5 JAN 2015 DOI: /caac

14 Question 3: All of the following are proven reasons to have a LDCT except: A) It provides a teachable moment for smoking cessation B) It relieves anxiety and guilt about smoking C) It reduces deaths D) LDCT greatly reduces radiation risk without compromising efficacy Question 3 All of the following are proven reasons to have a LDCT: A. It provides a teachable moment for smoking cessation B. It relieves anxiety and guilt about smoking C. It reduces deaths D. LDCT greatly reduces radiation risk without compromising efficacy 0% 0% 0% 0% A. B. C. D. 14

15 Complications after the Most Invasive Screening-Related Diagnostic Evaluation Procedure, According to Lung-Cancer Status. The National Lung Screening Trial Research Team. N Engl J Med 2011;365: NLST - Follow-Up After Screenings 24.2% of all screens had an abnormal result 96.4% of those were false positives 2.5% had invasive test for follow-up (bronchoscopy, thoracoscopy) 1.9% had a biopsy 61 complications, 6 of which were fatal, from 17,053 positive test results (0.4% adverse outcome rate) 7.5% of scans had incidental findings (not lung cancer) which were clinically significant 28 15

16 Cost (risks) v. Benefits Risks Radiation Costs False positive anxieties Unnecessary tests and invasive procedures Benefit 20 % reduction in lung cancer specific mortality & 6.9 % reduction in all cause mortality Radiation from Chest Imaging Equivalent dose, msv Equivalent # of CXRs (0.04 msv) CXR (PA & lat) 0.08 Mammogram 0.4 Chest CT scan Screening LDCT CTA for PE PET/CT Chest 2012;142:750 16

17 Incremental Cost Effectiveness of LDCT Lung Cancer Screening Black et al. N Engl J Med 2014;371: Cost Of Cervical, Colorectal, Breast, And Lung Cancer Screening Per Life-Year Saved Type Screening Cost per Date of Cost Technique life-year saved original study (2012 dollars) Cervical Pap smear 33, ,162 75,181 Colorectal Colonoscopy 11, ,705 28,95 Breast Mammography 18, ,309 51,274 Lung LDCT (baseline) 18, ,862 LDCT (lowest-cost) 11, ,708 LDCT (highest-cost) 26, ,016 Pyenson B S et al. Health Aff 2012;31:

18 True and False Positive Screens by Screening Round and Trial Arm CT CXR Round 1 N (%) Round 2 N (%) Round 3 N (%) Round 1 N (%) Round 2 N (%) Round 3 N (%) Total positives 7,193 (100) 6,902 (100) 4,054 (100) 2,387 (100) 1,482 (100) 1,175 (100) With lung cancer Without lung cancer 270 (4) 6,923 (96) 168 (2) 6,734 (98) 211 (5) 3,843 (95) 136 (6) 2,251 (94) 65 (4) 1,417 (96) 78 (7) 1,097 (93) Question 4: The simplest way to reduce the false positive rate of LDCT is: A) Do thinner cuts on LDCT B) Have 1 radiologist read all of the scans C) Use 6 mm nodule size cut off to define a positive scan D) Repeat the LDCT in 1 month for all positive scans 18

19 Question 4 The simplest way to reduce the false positive rate of LDCT is: A. Do thinner cuts on LDCT B. Have 1 radiologist read all of the scans C. Use 6 mm nodule size cut off to define a positive scan D. Repeat the LDCT in 1 month for all positive scans 0% 0% 0% 0% A. B. C. D. Cumulative Incidence of False-Positive Test Results in Lung Cancer Screening: A Randomized Trial Croswell Ann Intern Med. 2010;152(8):

20 Definition of a Positive Test Result in Computed Tomography Screening for Lung Cancer: A Cohort Study Henschke Ann Intern Med. 2013;158(4): Definition of a Positive Test Result in Computed Tomography Screening for Lung Cancer: A Cohort Study Henschke Ann Intern Med. 2013;158(4):

21 Consequences of Potential Nodule Thresholds Within the NLST 14 Threshold, mm Nodules, % Cancer, % Cancers, No Lung Cancer Risk Calculators Download the Lung Cancer Risk Calculator Download the Nodule Prediction Calculator (full version) Download the Nodule Prediction Calculator (parsimonious 21

22 Predictive model (AUC=0.754) Risk factor O.R. 95% C.I. p-value (Wald) Sex Female vs. male Age Per year of age Duration cigarette use Per year of use Dose intensity vs. < vs. < vs. < Family history of lung cancer Yes vs. none or unknown Airflow obstruction I vs. none II vs. none III-IV vs. none Radiographic emphysema Trace vs. none <.0001 Mild vs. none Mod-severe vs. none Wilson et al., AJRCCM 2008:178; Cause-Specific Hazard Models Used in the Risk-Prediction Model for Lung-Cancer Death in the Radiography Group of the NLST. Kovalchik SA et al. N Engl J Med 2013;369: Kovalchik NEJM 2013;369:245 22

23 Cumulative Screening Outcomes in the Low-Dose CT Group. Kovalchik SA et al. N Engl J Med 2013;369: Factors included in lung cancer risk prediction models Factor PP Bach PLCO M2012 Age X X X Duration of smoking X X X Smoking intensity X X X Smoking status X X Smoking quit time X X Sex Asbestos exposure X X Race or ethnic group Education Personal history of cancer Family history of lung cancer X X X X Chronic obstructive pulmonary disease Body-mass index X X 23

24 Positive Fraction 6-year lung cancer risk To anticipate your experience in a lung cancer screening program, respond to each of the following Currently smoking questions. How old are you? At what age did you become a regular cigarette smoker? Are you currently smoking cigarettes or have you quit? At what age did you last quit smoking cigarettes? During the entire time you smoked, how many cigarettes did you smoke daily, on average? Your Total Score is 0 (Risk Level 1). Refer to the Table to learn the experience of NLST participants who had a risk profile similar to yours. The Table shows lung cancer risk for each of four Risk Levels. The Table expresses risk as the percentage of NLST participants who received a lung cancer diagnosis in the six years after a low-dose computed tomography (LDCT) or conventional chest x-ray (CXR) screening. The Table shows the Range of Risk associated with the Scores covered by each Risk Level and the Average Risk observed in NLST. Range of Risk Average Risk Risk Level Score LDCT CXR LDCT CXR 1 ( 20%) ( 40%) ( 30%) ( 10%) Integrated plots of the predictiveness and classification performance of the models. Calibrated to NLST LDCT Calibrated to PLuSS Risk Percentile 24

25 Prevented Lung Cancer Death) Based on the Quintile of Risk Within the NLST 6 5-y Risk of Lung Cancer Death, % FP per Prevented Lung Cancer Death All ,648 5, > Number Needed to Screen Unresolved Questions Who should be screened Who should interpret the screening CT scans and whom do you respond to the results 25

26 Pittsburgh Lung Screening Study PLuSS Observational study of demographics, blood, spirometry and annual low-dose CT chest 2002 present Designed to construct high risk cohort for lung cancer studies Designed for population based study and blood/tissue acquisition for basic SPORE researchers Table 3. Univariable and Multivariable Cox Analysis Exploring the Independent Association of the Studied Variables with LC Diagnosis in the PLuSS Cohort P value HR 95% CI Univariable Cox analysis Age >60 vs. < Sex, male vs. female BMI <25 vs. > Pack-years >60 vs. < Active smoker Years of former smoker Family history LC, yes vs. no GOLD I-II vs. III-IV Emphysema, yes vs. no Multivariable Cox analysis Age >60 vs. < BMI <25 vs. > Pack-years >60 vs. < Emphysema, yes vs. no AJRCCM 2015;191:285 26

27 Figure 2. Kaplan-Meier survival curves showing the lung cancer risk profile of patients in the low- and high-risk groups from the derivation cohort. Patients in the high-risk group (chronic obstructive pulmonary disease lung cancer screening scores 7 10 points) have a significant higher probability of lung cancer diagnosis than those in the lower risk group. Published in: Juan P. de-torres; David O. Wilson; Pablo Sanchez-Salcedo; Joel L. Weissfeld; Juan Berto; Arantzazu Campo; Ana B. Alcaide; Marta García-Granero; Bartolome R. Celli; Javier J. Zulueta; Am J Respir Crit Care Med 191, Lung cancer ascertainment in P-IELCAP ( ) and PLuSS ( ) in terms of number of participants screened according to the strategy employed: NLST, NLST/E, P-IELCAP(E) or PLuSS(E). 27

28 From: Trends in the Proportion of Patients With Lung Cancer Meeting Screening Criteria JAMA. 2015;313(8): doi: /jama % 44% Figure Legend: Temporal Pattern of Coverage Proportion by US Preventive Services Task Force Screening Criteria in Olmsted County, Minnesota, Error bars indicate 95% confidence intervals. Date of download: 2/26/2015 Copyright 2015 American Medical Association. All rights reserved. Cases not meeting USPSTF criteria (220/393 = 56%) Age < 55 (13.5 %), > 80 (12.2 %) = 45% < 30 pack years (23%) = 37% Quit > 15 years (22%) = 40% JAMA. 2015;313(8):

29 Wilson et al. AJRCCM 2008;178:

30 Wilson et al. AJRCCM 2008;178: Nodule Management Probability of malignancy for nodules < 8mm is low but follow-up is often aggressive. Why? 1) Lack of knowledge, completeness or conformance with guidelines 2) Radiologists lack of knowledge of risk factors (ie, smoking) 3) Weight placed on nonspecific characteristics of nodules (shape, spiculation, calcification, location) 4) Community bias toward overly aggressive management of lung nodules 30

31 % CA (% prev) < 1 % (90 %) 1-2 % (5 %) 5-15 % (2 %) >15 % (2 %) LDCT Reporting System Standardized interpretation (LUNG-RADS) with automated letter to patient and ordering provider All positive results funneled to same person (CRNP) Teleconsultation or nodule clinic Pre-auth for costly (PET) or invasive procedures (?) 31

32 Components for High Quality Lung Cancer Screening 1) Collect data on all enrolled subjects, nodules detected, management & outcomes of testing including cancers diagnosed 2) > 90% of screened subjects must meet eligibility criteria 3) Consistent policy about frequency & duration of screening 4) LDCT in accordance with ACR-STR technical specifications 5) Structured reporting system (LungRADS) 6) Lung nodule management algorithms & monitoring 7) Smoking cessation Chest 2015;147:

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