goals of presentation review context of lung cancer screening—why is it important? review data...

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?