1. Lung Cancer Screening with Low Dose Computed Tomography Todd Robbins, MD Co-Director, Multidisciplinary Thoracic Oncology Program

2. Lung Cancer Deaths Most common cause of death from cancer worldwide Most common cause of death from cancer in men and women More deaths per year in USA then breast, colorectal and prostate combined Despite advances in diagnosis, staging and treatment only 18% of patients with lung cancer are alive at 5 years post diagnosis.

3. Evolution of Lung Cancer Screening Serial chest x-rays Serial sputum cytology Early efforts at CT screening

4. Early CT Screening Studies Negatives included uncontrolled and biased Positives included CT to be more sensitive for detecting cancerous and non-cancerous nodules. Low dose CT scan was an effective screening tool with radiation exposure decreased by 75-80% as compared to conventional diagnostic CT. Specific protocols in these studies showed potential harms of screening including unnecessary invasive procedures among patients could be minimized by relying heavily on non-invasive surveillance screening.

5. National Lung Screening Trial (NLST) Over 50,000 patients 33 US centers 54-74 years old 30 pack per year smoking history Former smokers having quit within 15 years Randomly assigned to 3 rounds of annual screening with low dose CT or Chest X-ray

6. Results of NLST Annual screening with chest x-ray did NOT reduce mortality when compared to no screening. 20% reduction of lung cancer mortality with low dose CT screening when compared to chest x-ray screening which was equivalent to no screening (247 vs 309 deaths per 100,000 patient years of follow-up). In absolute terms this translated to approximately 3 to 4 fewer deaths from lung cancer per 1,000 high risk patients who underwent LDCT screening. To put in context, the magnitude of benefit is at least as great if not greater as that reported for breast cancer mortality with annual mammographic screening among women 50-59 years old.

7. NLST Screening Details 39% of patients in LDCT group had at least 1 positive result. 95% of these were falsely positive Most of these patients had follow-up imaging and after 3 rounds of screening a small minority underwent invasive tissue sampling (needle biopsy 2%, bronchoscopy 4%, surgical biopsy 4%) 73% of the non-surgical biopsies were benign 24% of the surgical biopsies were benign 1% of the invasive tissue sampling patients had a complication but only 20% of the complications occurred in patients with benign disease.

8. Guidelines for Lung-Cancer Screening with Low-Dose CT Endorsement of Shared OrganizationYearTarget PopulationRecommendationDecision MakingAdditional Comments American Academy of Family Physicians2013 Persons with a high risk of lung cancer on the basis of age and smoking history Insufficient evidence to recommend screeningYes Screening cannot be recommended on the basis of a single study conducted in major medical centers American Association for Thoracic Surgery2012Not specified Screen should be conducted in environments in which there are multidisciplinary teams for managing indeterminate and positive screening scans; desirable to create a program that supports smoking cessation Tier 1 Persons 55-79 yr of age with >30 pack-yr smoking history Recommendation on the basis of data from well-designed randomized, controlled trials Tier 2 Persons 50-79 yr of age with >20 pack-yr smoking history and another risk factor for lung cancer Recommendation on the basis of data from nonrandomized trials Tier 3 Lung-cancer survivors who have completed 4 yr of surveillance without recurrenceConsensus opinion American Cancer Society2013Persons meeting the NLST criteria Discussion about screening should be initiatedYes Recommends only if there is access to a high volume, high-quality lung cancer screening and treatment center

9. Guidelines for Lung-Cancer Screening with Low-Dose CT (continued) Endorsement of Shared OrganizationYearTarget PopulationRecommendationDecision MakingAdditional Comments American College of Chest Physicians, American Society of Clinical Oncology, and American Thoracic Society2012Persons meeting the NLST eligibility criteria Grad 2B recommendation (i.e., conditional recommendation based on moderate-quality evidence) that screening should be offeredYes Suggest that screening be conducted in centers similar to those where NLST was conducted; screening is of a substitute for smoking cessation American Lung Association2012Persons meeting the NLST eligibility criteria Screening with low-does CT should be recommended Choice to undergo screening must be an individual one; every patient should have the information required to make an informed decision Patients should be referred to a facility that uses best practices for CT screening; smoking cessation is the best method of reducing lung cancer risk among those who smoke National Comprehensive Cancer Network2012 Patients should have a full understanding of risks and benefits Multidisciplinary screening programs will be helpful; smokers should always be encouraged to quit smoking Category 1Persons meeting the NLST eligibility criteriaHigh-level evidence Category 2B Persons >50 yr of age with >20 pack yr smoking history and one additional risk factor for lung cancerLower-level evidence and consensus opinion U.S. Preventive Services Task Force2013 Persons meeting the NLST eligibility criteria, with upper limit for age extended to 80 yr Grade B recommendation (moderate certainty of moderate net benefit)Yes Moderate net benefit depends on accuracy of image interpretation that is similar to the accuracy at NLST centers and resolution of most false positive results without invasive procedures; smoking cessation is the most important intervention to prevent lung cancer

10. LDCT Screening Recommendations December 2013, US Preventive Services Task Force April 2014, The Medicare Evidence Development and Coverage Advisory Committee Late 2014 – Early 2015, Centers for Medicare and Medicaid Services

11. Areas For Continued Discussion Optimization of selection of candidates for screening Uncertainty whether LDCT screening can be performed safely and effectively in real world practices Benefit of access to smoking cessation services in conjunction with screening

12. Lung Cancer Screening with Low-Dose Computed Tomography (CT) The National Lung Screening Trial (NLST) showed that screening with low-dose CT reduced the risk of death from lung cancer by 20% among persons 55 to 74 years of age who had a smoking history of at least 30 pack-years and were current smokers or were former smokers who had quit within the previous 15 years. Risks of screening include frequent false positive findings that often require CT surveillance and less commonly lead to invasive biopsy or surgery that reveals benign findings. Most guidelines recommend that high-risk smokers and former smokers be offered screening with low-dose CT and engaged in a process of shared, informed decision making to weigh the pros and cons and make an individualized choice There is concern that the favorable balance between the benefits and harms of screening observed in the idealized conditions of the NLST may be difficult to replicate when lung-cancer screening is introduced in diverse clinical practice settings. Current smokers should be advised that screening is not a substitute for smoking cessation. Patients with positive screening-testing results are more likely than those with negative results to quit smoking, but the effect of participating in a screening program on the rate of smoking cessation is uncertain.

13. LATE BREAKING NEWS Centers for Medicare and Medicaid Services (CMS) said Monday that LDCT would be reimbursed once per year for beneficiaries who fit the criteria of the National Lung Screening Trial (NLST) However, there were additional criteria: 1) Beneficiary would need a written order obtained during a “lung cancer screening counseling and shared decision making visit” from a physician, PA, Nurse Practioner, or Clinical Nurse Specialist. 2) Radiologist and imaging center criteria approval. 3) On subsequent screening, the written order could be from an annual wellness visit, tobacco cessation counseling visit, or other visit.