LUNG CANCER SCREENING - PDF Free Download

LUNG CANCER SCREENING Christopher Lettieri MD, FACP, FCCP, FAASM Pulmonary/Critical Care Consultant to the Surgeon General Professor of Medicine Walter Reed National Military Medical Center American College of Physicians Virginia Chapter March 2016

CONFLICT OF INTEREST DISCLOSURES 1. I do not have any potential conflicts of interest to disclose, OR 2. I wish to disclose the following potential conflicts of interest Type of Potential Conflict Details of Potential Conflict Grant/Research Support Consultant Speakers Bureaus Financial support Other 3. The material presented in this lecture has no relationship with any of these potential conflicts, OR 4. This talk presents material that is related to one or more of these potential conflicts, and the following objective references are provided as support for this lecture:

QUESTION Which of the following patients would you obtain CT scanning for lung cancer screening? A. 70 y/o with a 40 pack year history, quit 20 years ago B. 55 y/o current smoker with a 30 pack year history C. Both, but I would obtain a CXR before CT given the radiation risk and concern for future lymphoma D. Neither, I would not screen even high risk patients because screening asymptomatic patients leads to more invasive procedures, risks, and greater costs

LUNG CANCER 2 nd leading cause of cancer in the U.S. #1 cause of cancer-related death in U.S. 222,000 new cases in the U.S. annually 157,000 lung cancer-associated deaths World-wide 1.4 million deaths annually 600% increase in women over past 80 yrs

LUNG CANCER STATISTICS New Cases Deaths (#) Deaths (%) % of All Cancer Deaths Men 115,060 85,600 74.4 28 Women 105,070 71,340 67.9 26 Total 220,130 156,940 71.3 27 American Cancer Society, Cancer Statistics, 2011

US Death Rate (1000) US Death Rate (1000) US Incidence (1000) US Incidence (1000) LUNG CANCER STATISTICS New Lung Cancer - Men New Lung Cancer - Women 300 250 250 200 150 100 50 0 241 116 73 55 44 40 38 28 26 22 200 150 100 50 0 226 109 70 47 43 32 31 24 22 21 100 90 80 70 60 50 40 30 20 10 0 Lung Cancer Deaths - Men 87 28 26 18 13 13 12 10 10 8 Lung Cancer DeathsWomen 80 70 60 50 40 30 20 10 0 72 39 25 18 15 10 8 8 6 5

LUNG CANCER EARLY DETECTION MAY IMPROVE OUTCOMES Large # affected, high mortality rate Most diagnosed late in course of disease 75% present with symptoms due to advanced or metastatic disease not amenable to cure Overall five-year survival rates average 16% Stage I disease > 60% Stage IV disease < 5% Within early lung cancer (Stage I), there is a relationship between tumor size and survival

CT SCREENING FOR LUNG CANCER Earlier detection appears beneficial CXR is insensitive 74-79% of lung cancers missed on CXR Prior studies assessing CT screening did not find substantial benefit > harm New CT technology - lower radiation and cost Renewed Question- Does screening with lowdose CT (LDCT) reduce lung cancer mortality?

Over 250 trials published Radiographic LUNG CANCER SCREENING: A HISTORY OF FAILURE CXR (4 quality RCT, 1968-2010) CT (12 total RCT, 1995-2010) Other screening modalities have failed to show benefit but may have future role Sputum cytology Breath condensate Plasma markers

CT SCREENING FOR LUNG CANCER Initial Studies More identification of early stage (Stage I) lung CA No mortality benefit Lead time / Length time (over diagnosis) biases? Professional Guidelines 2007 ACCP: No evidence for regular screening National Cancer Institute: Inadequate evidence American Cancer Society: Not for routine use 2004 USPSTF: Insufficient evidence to recommend for/against Society of Thoracic Radiology: Not advocated

NATIONAL LUNG CANCER SCREENING TRIAL Prospective Randomized screening trial, CXR versus LDCT. 53,454 high risk participants at 33 institutions Inclusion Criteria Age: 55-74 years old Smoking hx: > 30pkyr hx (active or former who had quit within the previous 15 years) Exclusion Criteria Prior or existing lung malignancy CT Chest within 18 months prior to enrollment Hemoptysis Unexplained weight loss of > 15lbs in the preceding year Randomization CXR annually for 3 years (n = 26,732) LDCT annually for 3 years (n = 26,722)

NATIONAL LUNG CANCER SCREENING TRIAL CT CXR Abnormal Findings 24.2% 6.9% False Positive 96.4% 94.5% Other Clinical Significant Findings Detected 7.5% 2.1% Lung Cancers (total) 1,060 941 CA found on imaging 649 (61.2%) 279 (29.6%) Missed on Initial Screen (or developed after initial screen) 367 (34.6%) 525 (55.8%) NEJM 2011

Lung Cancer-Specific Mortality LDCT: 356 deaths (247 per 100,000 person-years) CXR: 443 deaths (309 per 100,000 person-years) Lung cancer cause of death in 25% of all patients 50% of those in CXR arm LDCT: 6.7% reduction in all cause mortality 20% reduction in mortality from lung cancer (p=0.004)

NATIONAL LUNG CANCER SCREENING TRIAL - SUMMARY CT did detect more cancers at earlier stage and lead to a 20% reduction in mortality But 320 persons need to be screened w/ LDCT to prevent 1 death High false positive rate CT 24.2% positive 4% True Positive, 96% False Positive CXR 6.9% positive 5% True Positive, 95% False Positive

LDCT arm complications 1.4% overall rate 0.06% of +CT w/o CA 11.2% of +CT w/ca 16 deaths 59 deaths per 100,000 Death from invasive diagnostic procedure LUNG CANCER SCREENING: RISK VS BENEFIT CXR arm complications 1.6% overall rate 0.02% of +CXR w/o CA 8.2% of +CXR w/ CA 10 deaths 37 deaths per 100,000 RR = 1.59 RRI = 0.59 or 59% ARI = 4.5 deaths per 100,000 person-years (recall ARR = 62 per 100,000 person-years) NNH = 22,222 person-years (4,444 @ T 5 )

BENEFITS OF CT SCANNING FOR LUNG CA Detects more cancers Finds cancer at smaller size/lower stage Results suggest improved survival Secondary effect improves smoking cessation Can identify other abnormalities

DOWNSIDE OF CT SCANNING FOR LUNG CA Identifies non-ca nodules that require following More CTs Risk for unnecessary procedures Psychologic impact Potential for over diagnosis Failure of screening (many Cancers missed) Increased costs Radiation exposure Lead time bias

DOWNSIDE OF CT SCANNING FOR LUNG CA Increase in unnecessary procedures and related complications UPitt program 34% of thoracotomies and VATS yielded non-ca diagnoses NELSON Study 27% invasive procedures for benign disease Wilson et al. AJRCCM 2008:956-961 Van Klaveren et al. NEJM 2009; 361

LEAD TIME BIAS Early detection leads to perception of increased survival without altering course Increased survival due to longer interval after a diagnosis is made with screening compared to one made after onset of symptoms

LENGTH TIME BIAS Screening detects clinically insignificant cancers Slow-growing cancers less likely to cause symptoms may be preferentially detected by screening

Theoretical risk of radiation-associated malignancy No epidemiologic studies demonstrate direct causality Average Radiation Dose: CXR PA/LAT (0.1 msv) Mammography (0.4 msv) LDCT Chest (1.5 msv) Diagnostic Chest CT (8 msv) Virtual Colonoscopy (10 msv) CTPA (15 msv) Very low risk for additional malignancy, lifetime (1/100,000)

USPSTF RECOMMENDATIONS

NCCN LUNG CANCER SCREENING GUIDELINES Low risk: <50y/o, <20pyh, no additional risk factors - not recommended Mod risk: >50y/o, >20pyh, no additional risk factors not recommended High risk: 55-74y/o, >30pyh (current or quit < 15 yrs) screen w/baseline LDCT High Risk-2: >50y/o, >20pyh + additional risk factosr - screen w/ baseline LDCT

ADDITIONAL RISK FACTORS Heavy second hand smoke exposure Radon exposure Prior malignancy especially lymphomas, cancer of the head and neck, and smoking-related cancers FH of lung cancer COPD Pulmonary fibrosis Occupational exposure silica, cadmium, asbestos, arsenic, beryllium, chromium, diesel fumes, and nickel

CURRENT RECOMMENDATIONS Consider/Offer annual lung cancer screening with LDCT for the following 55-74 years old (80y/o if healthy) 30 pack year history of of smoking current or quit within 15 years No other comorbidity that limits life-expectancy or treatment options willing to undergo curative treatment Continue until 81y/o; stopped smoking >15 years, or no longer healthy to undergo treatment ACCP, ACS, ALA, USPSTF, NCCN same recs except age limit