Lung Cancer Screening: To Screen or Not to Screen?

Transcription

1 Lung Cancer Screening: To Screen or Not to Screen? Lorriana Leard, MD Co-Director of UCSF Lung Cancer Screening Program Vice Chief of Clinical Activities UCSF Pulmonary, Critical Care, Allergy & Sleep Medicine Disclosures No financial disclosures Pulmonologist Co-Director of UCSF Lung Cancer Screening Program Member of National Comprehensive Cancer Center Lung Cancer Screening Guidelines Committee Overview Overview 1

2 American Cancer Society, Cancer Facts and Figures American Cancer Society, Cancer Facts and Figures Overview Single best way to prevent lung cancer deaths is to never start smoking, and if already smoking, to quit permanently. NLST 2011 American Cancer Society, Cancer Facts and Figures

3 Overview Why consider it? Is there a good screening test? Is it worth it? Why Lung Cancer Screening? Overall Survival for Non Small Cell Lung Cancer by Clinical Stage High prevalence (1 in 13 to 1 in 15 in US) High mortality #1 cancer killer in US #2 cause of death in US Risk factors to target screening Tobacco exposure Occupational history Family histroy Outcomes related to stage at diagnosis Goldstraw et. al. J Thorac Oncol Aug;2(8):

4 Ideal Screening Test Should Benefit screened individuals Increase life expectancy Detect disease when course can be altered with treatment NOT be dangerous / painful NOT have unacceptable FP results that necessitate invasive tests or cause anxiety NOT be harmful to the population who do not have the disease Patz et. al. NEJM 2000: 343; Bach et al. Chest 2003; 123: 72S-82S. And What About the? False-positive results: Detection of benign nodules requiring serial procedures Futile detection of small aggressive tumors or indolent disease Complications from diagnostic work-up Anxiety of test findings Radiation exposure Cost Potential Screening Tests Potential Screening Tests CXR: (6+ Large RCTs) Increased detection of early stage lung cancers But no reduction in mortality Sputum Cytology (with CXR) no reduction in mortality Chest CT Low Dose Chest CT Humphrey LL et. al. Lung cancer screening: An Update for the USPSTF

5 CXR vs. CT Low Dose Chest CT (LDCT) Early stage lung cancers are hard to visualize with conventional chest x-rays Investigators turned to CT in the hopes of finding more cases at an early, resectable (curable) stage CT Scan Observational Studies Sone et al. 1998, 2001 Sabue et al Nawa et al Study N Population Design Results Diedrich et al Swensen et al. 2002, 2003, 2005 (Mayo) Henschke et al. 1999, 2001, 2006 (I-ELCAP) 5,483 54% M (40-74) 46% smokers 1,611 88% M (40-79) 86% smokers 7,956 79% M (40-69) 77% smokers % M (40-79) All smokers % M (50-85) All 20pyr 31,567?% M (40-85) 83% smokers Annual x 2 yrs Q6 month x 5 yr Annual x 1 yr Annual x 2 yrs Annual x 4 yrs Annual x 1 yr 88% Stage I 77% Stage I 79% Stage I 85% Stage I 100% Stage I 58% Stage I 76% Stage I 61% Stage I 85% Stage I Screening by Low-Dose CT Observational studies of LDCT: 1. Detects more lung cancer than CXR 2. Majority of lung cancers detected are Stage I 3. Detects more non-cancerous than cancerous nodules 4. Incidence rate of new malignancy at annual screening is % Henschke, Clin Cancer Res

6 I-ELCAP Study in NEJM 2006 Survival and Stage Single arm observational study of 31,567 current or former smokers with LDCT Screening resulted in diagnosis of Lung Cancer in 484 subjects 412 (85%) Stage I Estimated 10 year survival rate was 88% (92% if resection w/in 1 mo.) Survival at 5 years All Patients Lung Cancer Survival and Stage 60 Stage I 5 Stage IV 80 Stage I (screened populations) Survival IELCAP Investigators. NEJM 2006; 355: Sries LAG et all. SEER Cancer Statistics Review, , National Cancer Institute ( Evaluation of Screening Test Screening test should be evaluated in randomized controlled trials (RCT) to minimize methodological biases. Lead-time bias Length bias Overdiagnosis Most important outcomes are diseasespecific and overall mortality (not just survival) NEJM June 29,

7 National Lung Screening Trial (NLST) Age years History of cigarette smoking > 30 pack yrs If former smokers, quit within 15 years Results of NLST Exclusions: Prior diagnosis of lung cancer Chest CT within 18 months Hemoptysis Unexplained weight loss NEJM June 29, 2011 NEJM June 29, 2011 NEJM June 29, 2011 Overview 7

8 Regular vs. Low Dose Chest CT Nodules are common Study Year # Patients % Nodules I-ELCAP , Lung Screening Study , Mayo , Milan , ELCAP , Nodules are common and the majority are benign NLST: initial CT screening Study Year # Patients % Nodules % Malignant I-ELCAP , Lung Screening Study , Mayo , Milan , % CTs positive (nodules 4 mm) Additional evaluation 80% imaging 4% Bronchoscopy 4% Surgery 2% CT guided biopsy ELCAP ,

9 Role of CT in initial work-up of nodule CT determines next step of w/u 1. Look for definitively benign features 2. Assess likelihood of malignancy 3. Determine next step in management Do nothing Benign Ca+ Fat CT follow-up Size <1.5 cm No malignant features Immediate action (surgery, biopsy, PET) Size >1.5 cm Malignant features (spiculation, growth) Benign patterns of calcification Old TB Old TB CT determines next step of w/u diffuse Hamartoma central Old cocci Do nothing Benign Ca+ Fat CT follow-up Size <1.5 cm No malignant features Immediate action (surgery, biopsy, PET) Size >1.5 cm Malignant features (spiculation, growth) popcorn concentric 9

10 Size and likelihood of cancer Spiculated border 89% nodules with spiculation = cancer Increased incidence of lymphatic and vascular invasion Occasionally seen with granulomatous diseases Adenocarcinoma Cocci Swensen. Radiology 2005; 235: 259 Malignant doubling time = 1-16 months Range for cancers = days Any growth suspicious 2 years of stability -> benign Growth 2/2011 8/2010 2/2010 2/2009 Density: which of the following is likely malignant? 10

11 Ground Glass Opacities (GGO) Nodule density % malignant Solid 11 Adenocarcinoma in situ Adenocarcinoma Mixed solid/ggo 48 GGO 59 Li. Radiology 2004; 233: 793 Ground glass +/- pseudocavitation Less associated with smoking Slow growth rate PET negative Dense Strongly associated with smoking Rapid growth rate Poor prognosis PET positive CT determines next step of w/u Follow-up recommendations Nodule size Low-risk patient High-risk patient Do nothing CT follow-up Immediate action (surgery, biopsy, PET) 4 mm No follow-up 12 months >4-6 mm 12 months 6-12 months months Benign Ca+ Fat Size <1.5 cm No malignant features Size >1.5 cm Malignant features (spiculation, growth) 6-8 mm 6-12 months months >8 mm 3 months 9 months 24 months 3-6 months 9-12 months 24 months 3 months 9 months 24 months Fleischner Guidelines. Radiology 2005; 237:

12 Follow-up of ground glass nodules 100% 5 yr survival of adenocarcinoma in situ Wedge resection (difficult to palpate) Average doubling time (days) Adenocarcinoma in situ: 567 Invasive adenocarcinoma with lepidic growth: 384 Squamous cell carcinoma: 122 Follow-up of ground glass nodules <5 mm no follow-up > 5 mm Initial follow-up at 3-6 months Subsequent yearly follow-up Development of solid components Overview False Positive CT: Complications of Invasive Procedures Major complication: 0.4% Thoracotomy, thoracoscopy, mediastinoscopy: 5.5% Bronchoscopy: 0.9% CT guided biopsy: 0% Death: <0.1% (6 in 17,053) NEJM June 29,

13 Radiation Risk Radiation Exposure Background radiation dose Background radiation dose in Denver 25 cross-country airplane flights Standard chest CT Low dose chest CT Tc-99m sestamibi 1 day stress/rest 3 msv/yr 5 msv/yr 1 msv 6 msv 1.5 msv 12 msv Low dose chest CT: UCSF low dose chest CT: 1.5 msv 0.7 msv What has made reduction of exposure possible? 4 MDCT > 16 MDCT > 64 MDCT ASIR (30-40% reduction) Veo (80% reduction) Overview No Lung Cancer Screening Recommended Until Now! Until the NLST, no screening modality had been identified to reduce lung cancer mortality Thus, until now, no recommendations for a screening strategy for lung cancer. 13

14 Lung Cancer Screening Guidelines May 20, 2012 in JAMA US Preventative Services Task Force American Society of Clinical Oncology American College of Chest Physicians American Cancer Society (interim statement) Have not yet incorporated NLST results into Guidelines National Comprehensive Cancer Network American Lung Association ACCP / ACSO Recommendation Lung Cancer Screening Guidelines For smokers and former smokers aged 55 to 74 years who have smoked for 30 pack-years or more and either continue to smoke or have quit within the past 15 years, we suggest that annual screening with low-dose computed tomography (LDCT) should be offered over both annual screening with chest radiograph or no screening, but only in settings that can deliver the comprehensive care provided to National Lung Screening Trial (NLST) participants. (Grade of recommendation: 2B.) JAMA. 2012;307(22). US Preventative Services Task Force 1. National Comprehensive Cancer Network 2. American Lung Association 3. American Society of Clinical Oncology American College of Chest Physicians American Cancer Society Has NOT yet incorporated NLST results into Guidelines Have published guidelines recommending Lung Cancer Screening under limited conditions 14

15 NCCN 2012 Guidelines: Initial Screening Lung cancer screening. J Natl Compr Canc Netw Feb 1; 10(2): NCCN 2012 Guidelines: Follow-Up ALA Guidelines: Counseling Patients Lung cancer screening. J Natl Compr Canc Netw Feb 1; 10(2): ALA Executive Summary April 23,

16 Overview about LDCT Lung Cancer Screening Optimal population for screening Cost-effectiveness of screening Optimal work-up for abnormal findings Optimal screening interval and number of years of screening Who should do the screening American Cancer Society Interim Guidance on Lung Cancer Screening Overview : Lung Cancer Screening Today Screening with LDCTs Detects early stage lung cancers in asymptomatic individuals Has high "false positive" rate leading to additional testing (serial imaging invasive procedures) Decreases lung cancer mortality by 20% and all cause mortality by 6.7%. 16

17 Recommendations for Lung Cancer Screening Today Wait for Recommendations by the US Preventative Services Task Force OR Recommendations for Lung Cancer Screening Today Follow strict criteria for high risk individuals Lung cancer screening CT scans should be at a center with radiologic, diagnostic, and treatment capabilities similar to those in the NLST trial Patient and physicians must be committed to close follow up Special Thanks to: Brett Elicker, MD Chief of Cardiac and Pulmonary Imaging for sharing his LDCT slides UCSF Lung Cancer Screening Program 17