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