Lung Cancer Screening

Michael I. Ebright, MD, FACS, FCCP Director, Thoracic Surgery, Stamford Hospital Attending Surgeon, New York-Presbyterian/Columbia

Lung Cancer Statistics —  Accounts for the most cancer-related deaths in both men and

women. —  Estimated 228,190 new cases and 159,480 deaths in 2013. —  27% of all cancer deaths. ACS Cancer Facts & Figures, 2013

of therapy and in assessing prognosis. A cancer’s stage is based on the size or extent of the primary (main) tumor and whether it has spread to nearby lymph nodes or other areas of the body. A number of different staging systems are used to classify cancer. A system of summary staging is used for descriptive and statistical analysis of tumor registry data. If cancer cells are present only in the layer of cells where they developed and have not spread, the stage is in situ. If cancer cells have penetrated beyond

percentage of cancer patients who are alive after some designated time period (usually 5 years) relative to people without cancer. It does not distinguish between patients who are cancerfree and those who have relapsed or are still in treatment. While 5-year relative survival is useful in monitoring progress in the early detection and treatment of cancer, it does not represent the proportion of people who are cured because cancer deaths can occur beyond 5 years after diagnosis.

Cancer Death Rates in Men Age-adjusted Cancer Death Rates*, Males by Site, US, 1930-2010 100 Lung & bronchus

Rate per 100,000 male population

80

60

Stomach

Prostate

Colon & rectum

40

20 Leukemia

Pancreas

Liver 0 1930

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

2000

2005

2010

*Per 100,000, age adjusted to the 2000 US standard population. Note: Due to changes in ICD coding, numerator information has changed over time. Rates for cancer of the liver, lung and bronchus, and colon and rectum are affected by these coding changes. Source: US Mortality Volumes 1930 to 1959 and US Mortality Data 1960 to 2010, National Center for Health Statistics, Centers for Disease Control and Prevention. ©2014, American Cancer Society, Inc., Surveillance Research

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Cancer Facts & Figures 2014

more likely to be diagnosed with cancer at a later stage, when treatment can be more extensive and more costly. The Affordable Care Act is expected to substantially reduce the number of people who are uninsured and improve the health care system for cancer patients. For more information on the relationship between health insurance and cancer, see Cancer Facts & Figures 2008, Special Section, available online at cancer.org/ statistics.

What Are the Costs of Cancer? The National Institutes of Health (NIH) estimates that the overall costs of cancer in 2009 were $216.6 billion: $86.6 billion for direct medical costs (total of all health expenditures) and $130.0 billion for indirect mortality costs (cost of lost productivity due to premature death). PLEASE NOTE: These numbers are not

Cancer Death Rates in Women Age-adjusted Cancer Death Rates*, Females by Site, US, 1930-2010 100

Rate per 100,000 female population

80

60

Lung & bronchus

Uterus† 40

Breast

20

Colon & rectum

Stomach

Pancreas

Ovary

0 1930

1935

1940

1945

1950

1955

1960

1965

1970

1975

1980

1985

1990

1995

2000

2005

2010

*Per 100,000, age adjusted to the 2000 US standard population. †Uterus refers to uterine cervix and uterine corpus combined. Note: Due to changes in ICD coding, numerator information has changed over time. Rates for cancer of the lung and bronchus, colon and rectum, and ovary are affected by these coding changes. Source: US Mortality Volumes 1930 to 1959 and US Mortality Data 1960 to 2010, National Center for Health Statistics, Centers for Disease Control and Prevention. ©2014, American Cancer Society, Inc., Surveillance Research

Cancer Facts & Figures 2014

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2010 Estimated cancer deaths

Lung Cancer Survival by Stage

IASLC  2012  

Lung Cancer Stage at Diagnosis

Overall Five-Year Survival only 17%!

Concept of Screening —  Screening is an intervention applied to a normal population —  Goal is to benefit the population —  Must weigh risks to healthy individuals against benefits to

those found to have disease —  Value is linked to: —  Likelihood that the target population will develop the disease —  Effectiveness of treatment

National Lung Screening Trial —  Funded by the National Institutes of Health (NIH) —  53,454 patients enrolled at 33 US medical centers —  Inclusion criteria

—  Age 55-74 —  30 pack-year smoking history —  Active smoker or quit within past 15 years

—  Randomized to Annual Chest X-ray or LDCT Scan for 3 years —  Mean follow-up 6.5 years

new england journal of medicine The

established in 1812

august 4, 2011

vol. 365

no. 5

Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening The National Lung Screening Trial Research Team*

A BS T R AC T Background

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of lowdose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. Methods

From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or sin-

The members of the writing team (who are listed in the Appendix) assume responsibility for the integrity of the article. Address reprint requests to Dr. Christine D. Berg at the Early Detection Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 3112, Bethesda, MD 20892-7346, or at [email protected]. * A complete list of members of the National Lung Screening Trial research team is provided in the Supplementary Appendix, available at NEJM.org.

Conclusion:     Ø  20%  reduc6on  in   lung  cancer   mortality   Ø  6%  reduc6on  in                in  overall  mortality   Ø  Number  needed  to   screen  (NNS)  to   prevent  one  lung   cancer  death  =  320   Ø  NNS  will  drop  in                by  focusing  on                different  cohorts  

NLST Stage by Modality

50% 49%

Organization

Age to Screen

Smoking History

Duration

Additional Patients

55-80

>30 pack years Active/ quit 30 pack years Active/ quit 30 py

Annual

Previously Lung Cancer Annual risk >5%

55-74

>30 py Active/quit 30 py Active/quit 30 py

Annually for 2 years, then biannually

None

Number Needed to Screen (NNS) —  Breast Cancer (Mammography) —  1224 women 40-74yo needed to screen to prevent one death

from breast cancer after 14y of observation

—  Humphrey et al. Ann Intern Med. 2002. USPSTF Summary

—  Colon Cancer (Endoscopy) —  871 patients 55-74yo needed to screen to prevent one death

from colorectal cancer after 3-5y observation —  Schoen et al. NEJM. 2012. 366: 25.

—  Lung Cancer (LDCT) —  320 patients (55-74yo smokers) needed to screen to prevent

one death from lung cancer after 2 years (3 screens) —  NLST. NEJM. 2011. 365: 5.

Individual vs Population Benefit —  Difficult concept to explain to patients —  20% reduction in lung cancer deaths —  16 instead of 20 per 1000 high-risk individuals will die of

lung cancer (20% reduction) —  98.4% chance of not dying of lung cancer vs. 98.0% chance

Why get screened? —  To discover disease at a treatable stage —  Does not prevent disease —  Personal reasons: —  Fear of cancer —  Relief from anxiety —  Reassurance they do not have the disease

Aggressivity vs. Interval Screening Interval

Symptomatic

LDCT Detectable

Tumor Burden

Time (years)

Positive Screen Results —  Rate of positive LDCT: 24% —  More than 90% of positive screening tests led to a diagnostic

evaluation, with the majority resolved with imaging alone —  96.4% were false positives (across 3 scans) —  Positive results generate: —  50% had follow-up CT scan —  8% underwent PET —  10% underwent some invasive procedure (percutaneous biopsy,

bronchoscopy, surgery)

Positive Screen Results —  All complications resulted from workup of suspicious

findings and/or surgery for lung cancer —  Major complications (e.g. pneumothorax, hemothorax)

occurred in only 1.4% of those undergoing procedures —  16 patients died within 60 days of an invasive procedure, 10

of whom had lung cancer and may have died from surgical complications or cancer progression

Risks of Screening —  False Positive Results —  Subsequent Procedural Risks —  Percutaneous biopsy —  Bronchoscopy —  Surgery

—  Overdiagnosis —  Radiation Exposure —  Anxiety

Overdiagnosis —  Overdiagnosis is the detection of a cancer that would not

cause symptoms or result in death over the patient’s lifetime. —  Is a byproduct of screening, which seeks to detect occult disease in asymptomatic individuals. —  Overdiagnosis can result in unnecessary treatment, morbidity, cost, and anxiety —  BUT, it is not possible to distinguish indolent lesions from aggressive tumors prospectively

Overdiagnosis

More than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer. False positives usually resolve with additional imaging, so overdiagnosis rates will decrease with additional scans.

Radiation Risk Procedure

Radiation

Background Radiation

4 mSv/yr

25 cross-country plane flights

1 mSv

Conventional Mammogram (2D)

0.7 mSv

3D Mammogram

1.4 mSv

Standard Chest CT

7 mSv

Low dose Chest CT

1.5 mSv

Cardiac Stress Test

12 mSv

•  For a 50 yo female with a 30 pack-year smoking history, 25 years of annual LDCT scans increases risk by 0.85%, compared with a 17% risk of lung cancer. •  For a similar 50 yo male, risk is increased by 0.23%, compared with a 16% risk of lung cancer. •  Death from radiation exposure- 1:2500; NNS for lung cancer death- 320 •  Radiation risk low but not negligible; main risk is radiation-induced lung cancer. Brenner DJ. Radiology 2004;231:440-5

Anxiety —  Potential adverse psychological effects of false positive screens or

significant incidental findings are a barrier to lung cancer screening —  False positives can occur at a rate of 20-50% —  Incidental findings occur at a rate of 6-14% —  Results from lung screening may not be as immediate as screening for breast or colon cancer, as time is often an important variable

—  2812 participants in NLST underwent

HRQoL, SF-36, and STAI forms at 1-month and 6-month timepoints —  No difference between negative, incidental finding, and false positive screens at 1 and 6 months —  Screening programs that include appropriate pre-screen counseling may have no significant psychological impact on participants who are free of lung cancer Gareen IF et al. Cancer 2014. Figure 2. Mean change in score from baseline and 95% confidence intervals: (A) Physical Component Score (PCS), (B) Mental Component Score (MCS), and (C) STAI Score by time point of data collection.

DISCUSSION

. Regression Analyses Examining the Association Between Change From Baseline (PCS and MCS) and Score (STAI)b and Screen nd Study Arm, Adjusted for Potential Confounding Factorsa

Anxiety

Cost of Screening —  Additional $1.3 - 2.0 billion to national health care

expenditure to avoid 8100 premature cancer deaths —  Additional cost of screening to avoid one lung cancer death is

$240,000 —  Assumes screening uptake rate of 50-75% among NLST-

qualified individuals Goulart BH et al., JNCCN, 2012.

Smoking Cessation —  The most important tool for prevention of lung cancer

death remains smoking cessation —  Lung Cancer Screening is considered a “teachable moment” where smoking cessation counseling may have a greater impact —  Several studies have shown that the cost-effectiveness of lung cancer screening may be significantly augmented by a concomitant smoking cessation program —  All lung cancer screening programs should be paired with an organized smoking cessation program

Interpretation of Results —  Lack of Standardization

—  Fleishner Guidelines? —  NCCN Guidelines? —  Nothing clearly designed for interpretation of screening scans in a

high-risk lung cancer population

—  Fear of underreporting and negligence —  Overuse of such phrases as “cannot exclude malignancy,”

“differential diagnosis includes malignancy,” “clinical correlation advised” —  Lung-RADS Version 1.0 —  American College of Radiology, released April 2014 —  Designed to standardize LDCT screening reporting and

recommendations

Lung RADS Version 1.0 Assessment Categories Release date: April 28, 2014

Category

Category Descriptor

Incomplete

Negative

Category

0 No nodules and definitely benign nodules

Findings prior chest CT examination(s) being located for comparison part or all of lungs cannot be evaluated

Management

Probability of Malignancy

Estimated Population Prevalence

Additional lung cancer screening CT images and/or comparison to prior chest CT examinations is needed

n/a

1%

Continue annual screening with LDCT in 12 months

< 1%

90%

6 month LDCT

1 2%

5%

3 month LDCT; PET/CT may be used when there is a 8 mm solid component

5 15%

2%

chest CT with or without contrast, PET/CT and/or tissue sampling depending on the *probability of malignancy and comorbidities. PET/CT may be used when there is a 8 mm solid component.

> 15%

2%

As appropriate to the specific finding

n/a

10%

no lung nodules 1

nodule(s) with specific calcifications: complete, central, popcorn, concentric rings and fat containing nodules solid nodule(s): < 6 mm new < 4 mm

Nodules with a very low

Benign likelihood of becoming a Appearance clinically active cancer due or Behavior to size or lack of growth

part solid nodule(s): 2

< 6 mm total diameter on baseline screening non solid nodule(s) (GGN): < 20 mm OR 20 mm and unchanged or slowly growing category 3 or 4 nodules unchanged for 3 months

Probably Benign

Probably benign finding(s) short term follow up suggested; includes nodules with a low likelihood of becoming a clinically active cancer

solid nodule(s): 6 to < 8 mm at baseline OR new 4 mm to < 6 mm 3

part solid nodule(s) 6 mm total diameter with solid component < 6 mm OR new < 6 mm total diameter non solid nodule(s) (GGN) 20 mm on baseline CT or new solid nodule(s): 8 to < 15 mm at baseline OR growing < 8 mm OR

4A

new 6 to < 8 mm part solid nodule(s: 6 mm with solid component 6 mm to < 8 mm OR

Suspicious

Findings for which additional diagnostic testing and/or tissue sampling is recommended

with a new or growing < 4 mm solid component endobronchial nodule solid nodule(s) 15 mm OR 4B

new or growing, and 8 mm part solid nodule(s) with: a solid component 8 mm OR

4X

Other

Prior Lung Cancer

Clinically Significant or Potentially Clinically Significant Findings (non lung cancer) Modifier for patients with a prior diagnosis of lung cancer who return to screening

a new or growing 4 mm solid component Category 3 or 4 nodules with additional features or imaging findings that increases the suspicion of malignancy

S

modifier may add on to category 0 4 coding

C

modifier may add on to category 0 4 coding

Lung-RADSVersion 1.0, American College of Radiology

IMPORTANT NOTES FOR USE: 1) Negative screen: does not mean that an individual does not have lung cancer 2) Size: nodules should be measured on lung windows and reported as the average diameter rounded to the nearest whole number; for round nodules only a single diameter measurement is necessary

Right Lower Lobe Nodule 61yo male 40 pack-year smoker Quit 3m ago 1.7cm nodule

Right Lower Lobe Nodule —  Would be considered LungRADS Category 4B —  Probability of malignancy >15% —  Recommend further workup (diagnostic CT, PET, possibly

tissue confirmation) —  Underwent right lower lobectomy and MLND —  Pathology: 1.8cm moderately differentiated adenocarcinoma

(w/ LVI), Stage IA (T1aN0M0) —  Likely screening success

Left Superior Segment GGO

2010: 17mm diameter 2014: 23mm diameter

Left Superior Segment GGO —  Would be considered LungRADS Category 2 —  Probability of malignancy