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