This document summarizes the evidence and guidelines for low-dose CT screening for lung cancer. It discusses the National Lung Screening Trial which found a 20% reduction in lung cancer mortality with low-dose CT screening in high-risk individuals. However, screening also led to many false positives in 96.4% of cases. Guidelines from the USPSTF recommend annual screening for ages 55-80 who have at least a 30 pack-year smoking history if they currently smoke or quit within the past 15 years. Primary care providers have an important role in facilitating shared decision making about the benefits and harms of screening.

1. Kathryn L. Bilello, M.D.
UCSF Clinical Professor of
Medicine
Low Dose CT Screening
for Early Diagnosis of
Lung Cancer

2. -Asymptomatic 64 y/o man with 39 pack-yrs smoking with
discontinuation 10 yrs ago. His father died from lung CA
-Patient’s internist arranged for a screening CT
T.K.

3. 200X

4. 200X TTF-1

5. T.K.
 Moderate-well differentiated adenoCA
of bronchogenic origin
 PFTs normal
 Staging w/u (PET-CT, MRI brain) neg
 Clinical Stage 1A (T1aN0M0)
 Underwent RUL lobectomy
 Final pathology showed poorly
differentiated adenoCA (2.8 cm) with
visceral pleural invasion and neg LN
 Pathologic stage 1B (T2aN0M0)
• 5 year survival almost 60%

6. Lung Cancer Screening
 Rationale for lung cancer screening
 National lung screening trial
 Harms of screening
 Guidelines for screening
 Components of a screening program
 Challenges of a screening program
 Role of primary care provider
 The future

7. Rationale for Lung Cancer Screening
 Lung cancer is the leading cause of
cancer deaths in US and globally
 75% of pts with lung CA present with
locally advanced or metastatic disease
– Overall NSCLC 5 year survival is 15%
 85% of lung cancer smoking-related
 37% of US adults current or former
smokers
 Low dose CT is sensitive at identifying
early stage lung cancers
– Early stage NSCLC 5 yr survival > 70%
ACS. Cancer Facts and Figures 2013

8. Original Article
Reduced Lung-Cancer Mortality with Low-Dose
Computed Tomographic Screening
The National Lung Screening Trial Research Team
N Engl J Med
Volume 365(5):395-409
August 4, 2011

9. National Lung Screening Trial
 RCT comparing LDCT with CXR on
death rate for lung cancer in high risk
population ( involved 33 sites in US)
 Current or former smoker (30 pk- yrs)
 Former smokers had to quit within 15
yrs of study entry
 Ages 55-75 years
 Enrolled 53,454 adults starting in 2002
 Screened annually for 3 yrs followed by
an average of 6.5 yrs of follow up

10. J Clin Oncol 2013; 31:1002-1008
National Lung Screening Trial Design

11. Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer.
The National Lung Screening Trial Research Team. N
Engl J Med 2011;365:395-409
356 in LDCT vs 443 in CXR
1060 in LDCT vs 941 in CXR

12. NLST Findings: The Good News
 20% decrease in lung cancer mortality
in LDCT group compared with CXR
 6.7% reduction in all-cause mortality
 Absolute risk reduction of 3 deaths per
1000 individuals screened
– 14 lung CA deaths not averted per 1000
– Must screen 320 individuals to save one life from
lung cancer
– Must screen 465-601 women with mammography
to save one life from breast cancer
 Stage shift to earlier stage lung CA
with LDCT (twice as many IA)

13. NSLT: The Bad News
 Almost 40% of those screened with
LDCT had a positive screen (nodule >
4 mm) during entire screening period
 Of the positive screens, only 3.6%
represented lung cancer
– false positive 96.4%
 More than 90% of positive screens in
first round of screening led to a
diagnostic evaluation
 Frequency of complications very low
– 1.4% in LDCT vs 1.6% in CXR

14. Benefits and Harms of CT Screening for
Lung CA: A Systematic Review
 Included 8 randomized trials and 18
cohort studies
 20% chance of detecting a nodule per
round of screening (across all trials)
 More than 90% of nodules are benign
(false-positive)
 Leads to further imaging (73% with FP
nodule in NLST) and invasive
procedures (1.2% with FP nodule in
NLST)
JAMA 2012; 307:2418-2429

15. Risks Associated with LDCT Screening
 False-positive results
 False-negative results
– In NLST (LDCT group) 6.2% of those dx
with lung CA had a false-negative screen
 Anxiety
 Radiation exposure
 Overdiagnosis
 Financial Costs

16. Radiation Exposure
 Mean dose in NLST per scan 1.4 mSv
– One fifth the dose of standard CT
– Annual ambient radiation dose 3 mSv
 Mean dose in mammography 0.7 mSv
 Based on risk models from atomic
bombings and medical imaging, LDCT
screening will cause one cancer death
from radiation per 2500 screened
 Risk is low but not trivial
JAMA 2012; 307:2418-2429

17. Overdiagnosis
 Detection of indolent cancers that may
never become symptomatic and are
only detected by screening
 Person dies with lung cancer not from
lung cancer
– Unnecessary surgery
 Using NLST data, more than 18% of
lung CA detected by LDCT were
indolent
– Improve discrimination with biomarkers,
volumetric imaging
JAMA Intern Med 2014; 174:269-274

18. Health Care Costs
 Medicare reimbursement rate $300 for
a CT used as bench mark for self- pay
 CT cost is only a small fraction of
downstream costs related to work up of
a positive screen
 NLST cost-effectiveness analysis
– $81,000 per quality-adjusted life year gained
– Falls below $100,000 threshold some experts
consider to be reasonable in US
– Cost effectiveness ratios vary widely based on
risk group and modeling assumptions
N Engl J Med 2014;371:1793-1802

19. Screening for Lung Cancer: U.S.
Preventive Services Task Force
Recommendation Statement
 Adults aged 55-80 yrs who have a 30 pack-
year smoking history and currently smoke or
have quit smoking within the past 15 years
 Screen annually until age 80 or have
discontinued smoking for 15 years
 Grade B recommendation
 Screening may not be appropriate for
patients with significant comorbidities
Ann Intern Med 2014; 160:330-338

20. USPSTF also recommends:
 Screening should occur in the setting
of an organized program
 Shared decision making with
discussion of benefits and risks
 Smoking cessation counseling
 Standardized approach to scanning,
image interpretation, and management
 Adherence to quality standards
 Maintenance of a registry
 Validation that outcomes are similar to
those reported in NLST

21. Components of a LDCT Screening
Program as Proposed by Major
Organizations
CHEST 2013; 143 (5) (suppl):e78S-e92S
CHEST 2015; 147(2):295-303

22. “In 2011, there were 8.9 million NLST-
eligible smokers and 20.3 million
NLST-ineligible smokers as well as 94
million current and former smokers
of all ages in the U.S.”
N Engl J Med 2013; 369:245-254

23. Who Is Paying For Screening?
 Affordable Care Act requires private
insurers to cover screening in 2015
– Based on the USPSTF grade B
recommendation for screening
 Medicare (effective February 2015)
– Covers yearly screening for medicare
beneficiaries aged 55-77
– 30 pack-years
– Current or former smokers (quit < 15 yrs)
– Written order for screening
– Also covers a visit for counseling and
shared decision making

24. Who Is Responsible for Initiating
Screening?
 Traditionally the role of PCPs
 Do PCPs have the knowledge, skills
and time to advise pts on screening?
– If not, how do we provide the tools?
 UCSF Fresno Lung Nodule Program
– Currently, LNP is not a screening program
– Infrastructure for screening already exists
– Once a LN is identified, pt can be referred

25. Key Elements to Include in a Conversation about Screening for Lung Cancer with the Use of
Low-Dose CT.
Gould MK. N Engl J Med 2014;371:1813-1820

26. Shared Decision Making
 Consider the individual’s risk profile
 Consider the risk for death from a
competing cause (other than lung CA)
 Consider patient preferences/anxiety

27. Optimizing risk profiles for
screening
 Applying risk models to screening
decreases the number needed to
screen, reduces false positive results
and maximizes the number of lung
cancer deaths preventable by LDCT
 Risk calculators (available on-line)
– Memorial Sloan Kettering
– Brock University

28. Features Included in a
Personalized Risk Calculator

29. Targeting LDCT According to Risk
of Lung-Cancer Death
N Engl J Med 2013; 369:245-54

30. Should screening be opened up to high risk
individuals who don’t meet NLST criteria?
 Improving Selection Criteria for Lung Cancer
Screening: The Potential Role of Emphysema
– Am J Respir Crit Care Med 2015; 191:924-931
 Lung Cancer in Pts with COPD: Development and
Validation of the COPD Lung CA Screening Score
– Am J Respir Crit Care Med 2015; 191:285-291
 Experience with a CT Screening Program for
Individuals at High Risk for Developing Lung CA
– Similar rates of lung cancer in NCCN risk group 2 (> 50 yrs
old, > 20 pk yrs, all former smokers, one additional RF eg
hx of smoking-related CA, FH lung CA in1st degree
relative, chronic lung disease, pulmonary carcinogen)
– J Am Coll Radiol 2015; 12:192-197

31. Lung Nodule Size
What Defines a Positive Screen?
 NLST defined diameter > 4 mm
positive
 In NLST, nodules 4-6 mm accounted
for almost 50% of positive screens but
were associated with lung cancer in
less than 1% of participants
 Lung RADS adopts 6 mm as the
minimum threshold for a positive
screen

32. Lung-Rads
 Lung-Reporting and Data System
 Analogous to BI-RADS which is used
to report breast imaging
 Standardized system for interpreting
and reporting LDCT screening exams
 Provides management algorithms
based on likelihood of malignancy
 Launched in 2014 (ACR website)

33. Lung-RADS
Ann Intern Med 2016; 162:485-491

34. Lung-Rads
 With Lung-Rads, it is estimated that
approximately 9 of every 10 persons
screened will not require further imaging
between annual scans
 Retrospective application of Lung-Rads to
previously screened populations (eg NLST)
associated with significant increase in PPV
of a lung nodule with a small decrease in
sensitivity (small number of lung CA missed)
 We await prospective performance of Lung-
Rads
Ann Intern Med 2015; 162:485-491

35. The Future of Lung Cancer Screening
 Optimizing risk profiles
 Improving lung nodule algorithms
– Capturing nodule phenotypes more
predictive of lung cancer
– Improving quantitative assessment of
growth (volumetric analysis)
 Incorporating biomarkers (exhaled breath or
serum)
– To identify whom to screen
– To determine likelihood of CA in a
screened nodule

36. Screening for Lung CA: Conclusions
 Lung cancer is prevalent and lethal
 20% U.S. popln continues to smoke
 LDCT screening offers the promise of
reducing the number of patients dying
from lung cancer
 Enthusiasm for screening must be
tempered by potential harms
 Best practice is to follow guidelines:
– Smoking cessation
– Shared decision making before LDCT
– Screen in context of a structured program

37. Prim Care Clin Office Pract 2014; 41:307-330

38. Prim Care Clin Office Pract 2014; 41:307-330