low dose ct screening for early diagnosis of lung cancer
TRANSCRIPT
Kathryn L. Bilello, M.D.UCSF Clinical Professor of
Medicine
Low Dose CT Screening for Early Diagnosis of
Lung Cancer
-Asymptomatic 64 y/o man with 39 pack-yrs smoking withdiscontinuation 10 yrs ago. His father died from lung CA-Patient’s internist arranged for a screening CT
T.K.
200X
200X TTF-1
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%
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
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
Original Article Reduced Lung-Cancer Mortality with Low-Dose
Computed Tomographic Screening
The National Lung Screening Trial Research Team
N Engl J MedVolume 365(5):395-409
August 4, 2011
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
J Clin Oncol 2013; 31:1002-1008
National Lung Screening Trial Design
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
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)
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
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
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
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 trivialJAMA 2012; 307:2418-2429
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 imagingJAMA Intern Med 2014; 174:269-274
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
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
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
Components of a LDCT Screening Program as Proposed by Major
Organizations
CHEST 2013; 143 (5) (suppl):e78S-e92SCHEST 2015; 147(2):295-303
“In 2011, there were 8.9 million NLST-eligible smokers and 20.3 million NLST-ineligible smokers as well as 94million current and former smokersof all ages in the U.S.”
N Engl J Med 2013; 369:245-254
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
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
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
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
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
Features Included in a Personalized Risk Calculator
Targeting LDCT According to Risk of Lung-Cancer Death
N Engl J Med 2013; 369:245-54
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
Lung Nodule SizeWhat 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
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)
Lung-RADS
Ann Intern Med 2016; 162:485-491
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
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
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
Prim Care Clin Office Pract 2014; 41:307-330
Prim Care Clin Office Pract 2014; 41:307-330