LUNG CANCER: MORE PREVALENT THAN YOU THINK

Anthony D Weaver MD

An Equal Opportunity University

Disclosures

Dr. Anthony Weaver has no relationships to disclose.

An Equal Opportunity University

Objectives

1. Analyze the current demographics of lung CA2. Examine common presenting symptoms of lung cancer.3. Discuss the pros and cons of screening for lung cancer in high risk individuals4. Describe appropriate follow up care for primary care patients with findings suspicious of lung cancer.

An Equal Opportunity University

Remember…

The best way to treat lung cancer is to prevent it by not smoking.

“There is an overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema and other serious diseases in smokers. There is no safe cigarette . . . cigarette smoking is addictive, as that term is most commonly used today.”

Philip Morris tobacco company, 1999

Analyze the current demographics of lung CA

Objective 1

An Equal Opportunity University

History

Early 1900s: lung cancer was extremely rare End of 1900s: prevalence second to prostate

cancer in men, breast cancer in women. Lung cancer has passed heart disease as the

leading cause of smoking-related mortality 159,480 deaths in 2013 (NCI lung cancer statistics)

An Equal Opportunity University

Top 5 Causes of Cancer Death for Men

1. Lung & bronchus 28%

2. Prostate 10%

3. Colon & rectum 8%

4. Pancreas 7%

5. Leukemia 5%

Cancer Facts and Figures 2014 at www.cancer.org

An Equal Opportunity University

Top 5 Causes of Cancer Death for Women

1. Lung & bronchus 26%

2. Breast 15%

3. Colon & rectum 9%

4. Pancreas 7%

5. Ovary 5%

Cancer Facts and Figures 2014 at www.cancer.org

An Equal Opportunity University

Kentucky Cancer Deathsper year 2006-2010

Lung and Bronchus 3416 Colon 881 Breast 597 Pancreas 507 Prostate 392 Leukemia 332 Non-Hodgkin Lymphoma 320 Ovary 212

National Cancer Institute State Data

An Equal Opportunity University

5-year survival rates 2001-2007

• 65% for colon cancer • 99% for prostate cancer• 89% for breast cancer• 16% for lung cancer

An Equal Opportunity University

Lung Cancer, 2004-2008

Region Incidence Rate Mortality RateUS* 62.0 52.5#

Kentucky** 100.8 75.1

The KY incidence is 62.6% HIGHER than the US

The KY mortality is 43.0 % HIGHER than the US *Source: SEER*Stat 7.0.4 SEER 17 Registries

**Source: Kentucky Cancer Registry#: Based on 2003-2007 rate

An Equal Opportunity University

Lung/Bronchus Cancer

Leading cause of cancer death in the US and KY. All 120 counties’ death rate above the US

average. The death rate varies from 59 in Larue and

Cumberland counties to 124 in Gallatin County. The highest rates are in eastern KY and

Ohio, Butler, and Muhlenberg counties.

An Equal Opportunity University

Smoking

Up to 90% of lung cancer cases are related to smoking.

9-15% are related to occupational exposure to carcinogens.

The strongest determinant of lung cancer is duration of cigarette smoking, and the risk becomes larger with more cigarettes smoked.

Smoking causes lung cancer in both men and women.

An Equal Opportunity University

Prevalence of Current Smoking by Area Development District, 2010

An Equal Opportunity University

Lung Cancer Incidence by Area Development District, 2004-2008

An Equal Opportunity University

Lung Cancer Mortality by Area Development District, 2004-2008

An Equal Opportunity University

Other Causes of lung cancer

Asbestos exposure Radon exposure Halogen ether exposure Chronic interstitial pneumonitis Inorganic arsenic exposure Radioisotope exposure, ionizing radiation Atmospheric pollution Chromium, nickel exposure Vinyl chloride

An Equal Opportunity University

Lung Cancer Incidence by Area Development District, 2004-2008

Lung Cancer in the Mountains

iLovemountains.org

Objective 2

Examine common presenting symptoms of lung cancer.

An Equal Opportunity University

Symptoms

Cough 50-75% Wt loss 8-68% Hemoptysis 25-50% Chest pain 27-49% Dyspnea 37-58% Hoarseness/stridor 2-18% Paraneoplastic Synd 10-20% Asymptomatic 7-10%

http://emedicine.medscape.com/article/279960-clinical

Discuss the pros and cons of screening for lung cancer in high risk individuals

Objective 3

An Equal Opportunity University

Screening for Lung CancerScreening with Chest XRAY/Sputum Cytology

Mayo Lung Project• 10,993 smokers: 6 year program of CXR and

sputum q 4 mos vs. annual CXR in the control group

• More cancers diagnosed in screened group but no mortality reduction at 20 yrs (actually higher in screened group

PLCO Cancer Screening Trial ( due 2015, aborted)

• 15,4942 participants (51.6 % current or former smokers)

• Single CXR at baseline and then annually x 3 yrs vs. “usual care” control group

• No difference in incidence or mortality• Only 20% of cancers detected by screening

An Equal Opportunity University

Study Overview Persons undergoing three annual screening

examinations with low-dose computed tomography had a 20% reduction in lung-cancer mortality compared with those screened with annual chest radiography.

An Equal Opportunity University

Study Design

Participants: Smokers/former smokers with a 30 pk-

yr history aged 55-75 years Exclusions: CT within 18 months of the

study, hemoptysis or and unexplained weight loss

53,454 participants: half assigned to CT group and CXR group

An Equal Opportunity University

Screening

Three yearly screenings with either low dose CT or PA/Lat CXRs and followed for 5.5 years

+ Scan included: • any non-calcified nodule or mass measuring

4mm or more• Adenopathy or effusion• If abnormalities were stable at 3rd screening,

they were classified as minor abnormalities

An Equal Opportunity University

Outcome measures

Primary: lung cancer mortality between the two groups

Secondary: death rate from any cause and the incidence of lung cancer in the two groups

Study 90% powered to detect a 21% decrease in mortality

An Equal Opportunity University

Results—stopped 11/10 due to benefit

Positive Result: • 24.2 % CT group, 23.3% were false + • 6.9 % CXR group, 6.5% were false +

False positive results:• 96.4% CT group, 94.5% CXR group

>90% of these resulted in further testing, most often further imaging

An Equal Opportunity University

Adverse events

Procedural complications (all)• 1.4% CT • 1.6% CXRMajor Complications (CT)• .06% (non-lung cancer group)• 11.2% (lung cancer group)Major Complications (CXR)

0.02% (non-lung cancer group)8.2% (lung cancer group)

An Equal Opportunity University

Lung Cancer Diagnosis

• 1060 lung cancers in CT group (645/100,000)• 941 lung cancers in CXR group (572/100,000) • Rate ratio = 1.13

Stage 1A and B Disease• 63% in CT group vs. 47.6% in CXR group• Fewer Stage 4 lesions in CT group than CXR

group

Mortality• 356 deaths from lung cancer in the CT group • 443 deaths from lung cancer in the CXR group• Signicant (20% reduction) in the CT group

(P=0.004)• Reduced all-cause mortality by 6.7% ( P=0.02).

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

Results of Three Rounds of Screening.

Diagnostic Follow-up of Positive Screening Results in the Three Screening Rounds.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Stage and Histologic Type of Lung Cancers in the Two Screening Groups, According to the Result of Screening.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Histologic Type of Lung Cancers in the Two Screening Groups, According to Tumor Stage.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Cause of Death on the Death Certificate, According to Screening Group.

An Equal Opportunity University

USPSTF recommendation

The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.

Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation)

An Equal Opportunity University

USPSTF recommendation

The magnitude of benefit depends on that person's risk for lung cancer… those who are at highest risk are most likely to benefit.

The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure.

False-positive LDCT results occur in a substantial proportion … 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results.

An Equal Opportunity University

USPSTF recommendation

The USPSTF found insufficient evidence on the harms associated with incidental findings.

A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosed—that is, they would not have been detected in the patient's lifetime without screening.

Radiation harms, including cancer …, vary depending on the age at the start of screening; the number of scans received; and the person's exposure to other sources of radiation.

An Equal Opportunity University

CMS Ruling

Since 2009, the CMS has been permitted to add coverage for "additional preventive services" if they are recommended (grade B) or strongly recommended (grade A) by the USPSTF and meet other requirements.

On February 10, 2014, the CMS opened a 30-day public comment period regarding coverage for lung cancer screening. The comments, coming primarily from healthcare providers, were overwhelmingly in favor.

After the public comment period ended on March 12, the CMS will convene a meeting of the Medicare Evidence Development and Coverage Advisory Committee to review the available evidence on lung cancer screening.

JAMA May 20, 2012, Vol 307, No. 22

An Equal Opportunity University

Radiation Exposure

LDCT exposure estimated 1.5 mSv per scan Total exposure estimated 8 mSv per subject Radiation-induced cancer 10-20 years later Benefit greater than risk for NLST group Risk greater than benefit for age ≤ 42

An Equal Opportunity University

Conclusion

“Screening a population of individuals at a substantially elevated risk of lung cancer most likely could be performed in a manner such that the benefits that accrue to a few individuals outweigh the harms that many will experience.

However, there are substantial uncertainties regarding how to translate that conclusion into clinical practice.”

N Engl J Med 368;8 February 21, 2013

Modified Logistic-Regression Prediction Model (PLCOM2012) of Cancer Risk for 36,286 Control Participants Who Had Ever Smoked.

Tammemägi MC et al. N Engl J Med 2013;368:728-736

Tammemägi MC et al. N Engl J Med 2013;368:728-736

N Engl J Med 369;3 July 18, 2013

An Equal Opportunity University

NEJM July 18, 2013

Only 1% of CT-prevented lung-cancer deaths occurred among the 20% at lowest risk

161 patients in the highest-risk quintile would need to be screened to prevent 1 lung cancer death.

In the lowest-risk quintile, 5,276 would need to be screened to prevent 1 lung cancer death.

An Equal Opportunity University

Marty Driesler Project

When compared to the NLST participants, MDLCP participants had higher smoking rates, lower income, lower education level and older age

“Can the US healthcare system afford this screening — what health services should be eliminated to pay for this very expensive endeavor (like childhood immunizations)?”  

An Equal Opportunity University

Lung Cancer: Why the Guilt Trip?

Memorial Sloan-Kettering survey 2000 lung cancer patients 84% current non-smokers “… people who start smoking are generally 12 or

13years old… They were targeted.” “We are going to be faced with an epidemic of lung

cancer for a decade or more if every single person stops smoking today.”

An Equal Opportunity University

Cancer Research—2012 (Federal dollars)

$21,000 per breast cancer death $1400 per lung cancer death.

Describe appropriate follow up care for primary care patients with findings suspicious of lung cancer.

Objective 4

An Equal Opportunity University

Follow-up of pulmonary nodules

Lesion Size Probability of Cancer< 5 mm 0-1%5 -10 mm 6-28%11-20 mm 33-60%21-30 mm 64-82%

Chest 2007; 132 [3 Suppl]: 94S-107S

An Equal Opportunity University

Characteristics of pulmonary nodules

Triangular shape, abutting a fissure

Central calcification

Spiculated nodule Noncalcified Part solid

Benign disease Malignancy

Chest 2007; 132 [3 Suppl]: 94S-107S

Tammemägi MC et al. N Engl J Med 2013;368:728-736

An Equal Opportunity University

PET Scanning

Average sensitivity 0.97 and specificity 0.78 for detecting a malignancy was reported

Useful for searching for systemic spread More sensitive, specific, and accurate than CT scan

for staging mediastinal disease PET scans may influence staging in up to 60% of

cases

An Equal Opportunity University

Population-Based Risk for Complications After Transthoracic Needle Lung Biopsy of a Pulmonary Nodule: An Analysis of Discharge Records*

Retrospective study of 15,856 adults who had a transthoracic needle biopsy of a pulmonary nodule

1.0% of biopsies complicated by hemorrhage 15% pneumothorax 6.6% of all biopsies pneumo + chest tube Those with any complications had longer lengths of stay

(P<0.001) and were more likely to require mechanical ventilation (P = 0.020)

*Soylemez Wiener, et al. Ann Int Med.2011: 155:137-144

Complications after the Most Invasive Screening-Related Diagnostic Evaluation Procedure, According to Lung-Cancer Status.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Complications after the Most Invasive Screening-Related Diagnostic Evaluation Procedure, According to Lung-Cancer Status.

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

An Equal Opportunity University

Remember…

The best way to treat lung cancer is to prevent it by not smoking.

“There is an overwhelming medical and scientific consensus that cigarette smoking causes lung cancer, heart disease, emphysema and other serious diseases in smokers. There is no safe cigarette . . . cigarette smoking is addictive, as that term is most commonly used today.”

Philip Morris tobacco company, 1999