goals of presentation review context of lung cancer screening—why is it important? review data...
TRANSCRIPT
Lung Cancer Screening
Wisconsin Cancer Council SummitMay 28, 2015
William Hocking, M.D.
Goals of PresentationReview context of lung cancer screening—why
is it important?
Review data from NLST supporting screening with low-dose CT (LDCT) scanning
Discuss the pros and cons of LDCT screening and current guidelines
Review the components of a lung cancer screening program
Cancer ScreeningFundamental principle: detection of cancer at
an early, asymptomatic stage will result in more effective treatment and reduced cancer-specific mortality
Ideal screening program Target high risk individuals Use a cost-effective test Exclude individuals without clinically significant
abnormalities
Lung Cancer Epidemiology14% of all US cancers
Leading cause of cancer-related mortality 1.4 million annual deaths worldwide 160,000 annual deaths in U.S.
27% of all cancer deathsExceeds deaths due to colorectal, breast, prostate and
pancreatic cancers combinedLung cancer among never-smokers would be the 6th-8th
most common cause of cancer mortality
Seigel R, CA J Clinicians 2014; 64: 9
Lung Cancer in Wisconsin
4020 estimated cases 2014
3000 estimated deaths 2014
192-257 cases annually seen at Marshfield Clinic
Lung Cancer Risk Factors Environmental factors
Tobacco smoking 85-90% of lung cancers occur in smokers Relative risk 20-30x
Radon222 exposure Indoor cook stoves Other exposures (e.g. asbestos, silica, arsenic) Diet ?
Host factors Family history Specific genetic polymorphisms or mutations Chronic lung disease
Effect of Smoking Cessation on Lung Cancer Incidence
Smoking Status Risk Ratio
Men Women
Current Smoker 1.00 1.00
Quit < 10 years 0.66 0.69
Quit 10-19 years 0.44 0.21
Quit 20-29 years 0.20 0.051
> 30 years 0.10
Never-smoker 0.03 0.051For women > 20 years
Peto R, et al BMJ 2000; 321: 323-9
NSCLC Prognosis
Stage Frequency 5 Year Survival (%)
0 NA 100
IA10
75
IB 55
IIA20
50
IIB 40
IIIA30
15-35
IIIB 5-10
IV 40 5-10
Goals of PresentationReview context of lung cancer screening—why
is it important?
Review data from NLST supporting screening with low-dose CT (LDCT) scanning
Discuss the pros and cons of LDCT screening and current guidelines
Review the components of a lung cancer screening program
Lung Cancer Screening
Until 2010, no evidence existed for a mortality
benefit from screening with chest x-ray, lung CT scanning
or sputum cytology
October 2010 results of the National Lung Screening Trial
(NLST) initially announced followed by a full report
published online June 29, 2011 and in print August
2011
National Lung Screening Trial (NLST)
Randomized, controlled trial comparing low dose CT scans (LDCT) to chest radiograph (CXR) annually for 3 years in high risk population
Powered to detect 20% reduction in lung cancer- specific mortality
55,434 randomized (2520 @ Marshfield Clinic)
Screening conducted at 33 sites in US 2002-2007
NLST Research Team, NEJM 2011; 365: 395
National Lung Screening Trial (NLST) Eligibility and Exclusions
Eligibility Age 55-74 years 30 pack-years smoking history Former smokers quit 15 years
Exclusions Previous lung cancer diagnosis Chest CT within 18 months Hemoptysis Unexplained weight loss >15 lbs.
NLST Research Team, NEJM 2011; 365: 395
“Positive” LDCT Screen in NLST
Non-calcified nodule > 4 mm (97.6% of positives)
Adenopathy
Pleural effusion
Consolidation, atelectasis
NLST ResultsScreen positivity
T0 27.3% T1 27.9% T2 16.8%
False positivity 96.4% of positive screens are false + Of all LDCTs, 23.3% false +
NLST ResultsWith median follow-up 6.5 years, cancer deaths
LDCT 247 CXR 309
13% excess of lung cancers in LDCT arm—possible overdiagnosis
63% of cancers in LDCT arm stage IA-IB
Number needed to screen to prevent 1 death=320
20% mortality reduction
NLST Research Team, NEJM 2011; 365: 395
NLST Lung Cancer Mortality
NLST Research Team, NEJM 2011; 365: 395
?Overdiagnosis
Complications in NLST
Complicationsa LDCT (%) CXR (%)
Total 1.4 1.6
Patients without lung ca
0.06 0.02
Patient with lung ca 11.2 8.2
Death within 60 days of procedure
1.5 3.9
aMajor: respiratory failure, anaphylaxis, cardiac arrest, BP fistula, MI, CVA, hemothorax, empyema, thromboembolism, brachial plexopathyIntermediate: blood loss, fever, infection, pain, arrhythmia, vocal cord injury or paralysis, pneumothoraxMinor: allergic reaction, bronchospasm, vasovagal reaction, subcutaneous emphysema, ileus
Lung Cancer ScreeningNLST cited as 1 of 10 most important advances in
2011
Estimated potential to save ≈30,000 lives annually in US
Goals of PresentationReview context of lung cancer screening—why
is it important?
Review data from NLST supporting screening with low-dose CT (LDCT) scanning
Discuss the pros and cons of LDCT screening and current guidelines
Review the components of a lung cancer screening program
LDCT Lung Cancer ScreeningPros and Cons
PROS CONS
Reduced lung cancer mortality False + LDCT, resulting in: Anxiety, stress Unnecessary testing
Overdiagnosis
Morbidity and mortality from diagnostic evaluations
Teachable moment for smoking cessation
Radiation exposure and risk of 2nd malignancy
False – examinations
Cost to healthcare system
OverdiagnosisDetection of cancer (usually through screening)
that would not otherwise have become apparent during the individual’s lifetime
Results in unnecessary treatment, morbidity, cost, anxiety and labeling of patient with diagnosis
Occurs in all forms of cancer screening
Overdiagnosis in LDCT Screening
Estimates of overdiagnosis rate NLST 18-22% (comparison of screened to control
arm) COSMOS 25% (based on volume doubling time)
Implications These are probably maximum estimates based on
3-7 years follow-up “Overdiagnosed” cancers predominantly indolent A high proportion of “overdiagnosed” lung
cancers are broncho-alveolar (lepidic growth) carcinomas
LDCT ScreeningRadiation Risk
Radiation exposure LDCT Screening exam (non-contrast) 1.5 mSv (comparable to 6
months normal background radiation) Diagnostic chest CT 7 mSv (2 years background radiation)
Radiation-induced lung cancer risk Individual 0.2-1.0% estimated risk Population estimates
1.8% increase in lung cancers, if 50% of eligible patients are screened over 25 years (Brenner DJ)
3-6 cases/100,000 screened patients over 15-20 years (International Commission on Radiologic Protection)
11.7-20.5 fatal lung cancers/100,000 screened (Italung-CT Trial)
Conclusion: there is some increased individual risk and greater population risk, but benefits of screening outweigh this risk
LDCT Screening Recommendations 2014
Organization 10 Population Other Considerations
USPSTF(2013)
Age 55-80a + >30 pack-years; quit <15
years
NA
AATS(2012)
Age 55-79 + >30 pack-years
Age>50+ 20 pack-years + additional risk
factorb; or lung ca survivor >5 years
ASCO-ACCP(2012)
Age 55-74 + >30 pack-years; quit <15
yearsc
NA
ACS(2013)
Age 55-74 + >30 pack-years; quit <15
yearsc
NA
NCCN(2011)
Age 55-74 + >30 pack-years; quit <15
yearsc
Age >50 + 20 pack years + additional risk
factord
aBased on modeling predictionsbCOPD, environmental or occupation exposure, prior cancer, thoracic RT, genetic or family historycNLST eligibility criteriadcancer history, lung disease, family history of lung ca, radon or occupational exposure
USPSTF Recommendations
Lung Cancer ScreeningCoverage
ACA requires private insurance coverage without cost-sharing for USPSTF “A” or “B” recommendations
CMS coverage decisions are independent of ACA requirement
LDCT Lung Cancer ScreeningCMS (Medicare) Coverage
Medicare Evidence Development and Advisory Committee (MEDCAC) recommended against approval 4-30-14, based on Complications of screening Radiation exposure Uncertainty about benefit of screening in
Medicare-aged population
NLST Results by AgeParameter 65+ <65
PPV 4.9% 3.0%
Screen-detected cancer
394/104 188/104
Lung cancer resection
Overall 73.2% 75.6
Stage I 93.0% 96.9%
Surgical mortality 1.0% 1.8%
False + 27.7% 22.0%
Invasive procedures after false+
3.3% 2.7%
5-year all cause survival
55.1% 64.1%
NNTS to prevent 1 death
245 364Pinsky PF, et al Ann Int Med 2014; 161: 627-33
NLST Results by AgeLDCT screening is more efficient in the 65+ age
group (but no data on patients >76 years old at time of screening)
Higher false + rate in 65+ group
Higher rate of invasive diagnostic procedures in 65+ group, but equivalent ratio of invasive procedures to lung cancer deaths averted (5.9) in both age groups
Both age groups had comparably high rates of surgical resection and low surgical mortality; this may in part reflect a “healthy volunteer” effect Pinsky PF, et al Ann Int Med 2014; 161:
627-33
NLST and AgeTake Home Message
“. . . LDCT screening seems to involve similar tradeoffs for persons who meet NLST eligibility criteria in both the older and younger age groups. Until there is new and direct evidence to the contrary, it does not seem reasonable to exclude persons aged 65 to 74 years from access to screening.”
Gould MK, Ann Int Med 2014; 161: 672-3
LDCT Lung Cancer ScreeningCMS (Medicare) Coverage
CMS approval 2-5-15 “. . . evidence is sufficient to add a lung cancer
screening counseling and shared decision making visit, and for appropriate beneficiaries, annual screening for lung cancer with low dose computed tomography (LDCT), as an additional preventive service benefit under the Medicare program . . .”
LDCT ScreeningCost-Effectiveness
Incremental cost-effectiveness ratios $52,000/life-year gained $81,000/quality life-year gained
Higher cost-effectiveness Women Higher risk individuals Current vs former smokers Older age
Estimates vary with assumptions
Adding smoking cessation program improves cost-effectiveness estimates
Black WC, et al NEJM 2014; 371: 1793-802
LDCT Screening CostMarshfield Clinic
Standard fee $250
Covered by WI Medicare and Medicaid
Commercial coverage variable
Much of the total screening-related cost results from diagnostic evaluation of positive LDCTs
How Can We Improve Efficiency and Effectiveness of LDCT
Screening? Improve selection criteria by refined risk
prediction models PLCO M2012 (Tammemagi MC, et al NEJM 2013)
Liverpool Lung Project Risk Model (Raji OY, et al Ann Int Med 2012)
Use of modified criteria for positive scans—e.g. Lung-RADS (Pinsky PF, Ann Int Med 2015)
How Can We Improve Efficiency and Effectiveness of LDCT
Screening? Improve selection criteria by refined risk
prediction models PLCO M2012 (Tammemagi MC, et al NEJM 2013)
Liverpool Lung Project Risk Model (Raji OY, et al Ann Int Med 2012)
Use of modified criteria for positive scans—e.g. Lung-RADS (Pinsky PF, Ann Int Med 2015)
Targeting LDCT Screening by Risk of Lung Cancer Death
5 year lung cancer death risk quintiles Q5 > 2.00% Q4 1.24-
2.00% Q3 0.85-
1.23% Q2 0.56-
0.84% Q1 0.15-
0.55%Kovalchik SA, et al NEJM 2013; 369: 245-54
PLCOM2012
Modified logistic regression prediction model for lung cancer risk
Model variables: age, race, education, BMI, COPD, history of cancer, family history of lung cancer, smoking status, smoking intensity, duration of smoking, smoking quit time
Selection CriteriaNLST vs PLCOM2012
Tammemagi MC, et al NEJM 2013; 368: 728-36
How Can We Improve Efficiency and Effectiveness of LDCT
Screening? Improve selection criteria by refined risk
prediction models PLCO M2012 (Tammemagi MC, et al NEJM 2013)
Liverpool Lung Project Risk Model (Raji OY, et al Ann Int Med 2012)
Use of modified criteria for scan assessment—e.g. Lung-RADS (Pinsky PF, Ann Int Med 2015)
Lung-RADS Nodule Surveillance
http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/LungRADS/AssessmentCategories.pdf
Application of Lung-RADS to NLST
Parameter Baseline (%) After Baseline (%)
Lung-Rads
NLST Lung-Rads
NLST
Sensitivity 84.9 93.5 78.6 93.8
False + 12.8 26.6 5.3 21.8
PPV 6.9 3.8 11.0 3.5
NPV 99.81 99.90 99.81 99.93
Retrospective application of Lung-RADS criteria to NLST
75% reduction in false +
Uncertain impact of sensitivity on lung cancer mortality
Pinsky PF, et al Ann Int Med 2015
Goals of PresentationReview context of lung cancer screening—why
is it important?
Review data from NLST supporting screening with low-dose CT (LDCT) scanning
Discuss the pros and cons of LDCT screening
Review the components of a lung cancer screening program
Implementation of LDCT Screening Program
American College of Chest Physicians and American Thoracic Society issued policy statement October 2014
Nine essential components of LDCT screening program
Mazzone PJ, et al Chest 2014
ACCP/ATS Principles for High-Quality Lung Cancer Screening
Programs Use of existing guidelines such as USPSTF to determine
who to screen, how frequently and how long
Use of ACR-STR specifications for performance of LDCT
Use of consistent definition of “positive” LDCT exam
Use of structured reporting system, such as Lung-RADS
Availability of multi-disciplinary clinical team for management of lung nodules and lung cancers
Use of evidence-based nodule management algorithms
Mazzone PJ, et al Chest 2014
ACCP/ATS Principles for High-Quality Lung Cancer Screening Programs-2
Inclusion of smoking cessation program with screening
Standardized communication to referring provider and patient
Patient and provider education programs are part of screening program
Data collection (nodules, cancers, complications)
Support for research into all aspects of lung cancer screening
Development of multi-society/multi-disciplinary oversight and credentialing body
Mazzone PJ, et al Chest 2014
LDCT Screening—Many Questions Remain
Who should be screened (what are optimal selection criteria)?
How frequently should screening occur?
When should screening begin, and how long should screening continue?
What are the health risks of LDCT screening, including radiation exposure?
Can LDCT be combined with biomarker studies to improve effectiveness?
Future Role of Biomarkers
Currently no established role in screening
In the future will likely be helpful Risk models Screening
Summary Lung cancer is the #1 cause of cancer mortality
Data from NLST demonstrate a 20% mortality reduction from LDCT screening of high-risk population
In appropriate populations, the benefits of screening outweigh the harms
LDCT screening now covered by CMS and most insurers
Implementation of an effective screening program is complex and requires multi-disciplinary collaboration, organization, data collection, quality improvement
There remain many unanswered questions that can be addressed by continued data collection and research
WCC should support and monitor development of high-quality lung cancer screening programs in Wisconsin
Thank You For Your Attention
Questions?