What to know and what to make of it

Transcription

1 Lung Cancer Screening: What to know and what to make of it J. Matthew Reinersman, MD Assistant Professor of Surgery Division of Thoracic and Cardiovascular Surgery Department of Surgery University of Oklahoma Health Sciences Center Director, Lung Cancer Screening, Stephenson Cancer Center Attending Physician, Thoracic Surgeon, VA Medical Center, Oklahoma City, OK

2 DISCLOSURE I have no financial relationships or affiliations to disclose. I have no conflicts of interest.

3 Outline Background Observational studies with LDCT Randomized trials with LDCT NSLT- study design and findings Critical issues with screening trials Nodule Management

4 American Cancer Society s estimates for lung cancer in the United States for 2014 About 224,210 new cases of lung cancer (116,000 in men and 108,210 in women) An estimated 159,260 deaths from lung cancer (86,930 in men and 72,330 among women), accounting for about 27% of all cancer deaths

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6 Lung Cancer Survival- 30 years Breast Prostate Colon Lung

7 Oklahoma Statistics 25 th 7 th

8 Stage at presentation Stage IV Stage II or III Stage I ADVANCED LOCALLY ADVANCED LOCALIZED

9 Lung Cancer why screen?? Dismal overall 5-year survival 16% in US (10 % in Europe) Presence of metastatic disease at diagnosis in > 70 85% Local / systemic Major reason for treatment failure 5 year survival of patients with Stage I A is > 70%

10 Historical Notes - Early Screening Trials

11 Historical Notes Early Screening Used CXR and sputum cytology Funded by the US National Cancer Institute in the 1970 s. 3 RCT s (JHH, MSK, Mayo) Mayo Lung Project - screening arm diagnosed early stage cancer 69 % vs 54%. Did not reduce lung cancer mortality 25 year follow up overall mortality higher in the screening arm, not significant.

12 Eras of Lung Cancer Squamous Cell Carcinoma previously more prevelant More centrally located More likely to provide positive sputum cytology

13 Eras of Lung Cancer Squamous Cell Carcinoma previously more prevelant More centrally located More likely to provide positive sputum cytology Adenocarcinoma is more prevalent today Often peripherally located Smaller nodules/ Ground Glass Opacities (GGOs)

14 Spiral CT Introduced new perspective in early detection In 2000, NCI feasibility study (LSS) N = 3318 Low dose CT detect more lung cancer than CXR 48% were Stage I Served as the basis for the National Lung Cancer Screening Trial

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16 Stage I lung cancer identified

17 Observational Studies Henschke (ELCAP) 1999 Sone 2001, Nawa 2002 Sobue 2002 Swensoen 2003 Pastorino 2003 Diederich 2004 Bastarrika 2005 Chong 2005, Novello 2005 MacRedmond 2006 I ELCAP 2006 Callol 2007, Veronesi 2008 Wilson 2008, Menezes 2010 N = 71, 935 Median age 59 Pack Years 41 Nodule rate 14, 890 (21 %) Lung Cancer Detection 1% (range 0.2 % to 2.7%) Stage I cancers 78 %

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22 Lung Cancer screening: Design of randomized LDCT trials Study Country Design Year Started Subjects Enrolled Age Range Number of CT s LSS USA CT vs CR , DANTE Italy CT vs Obs , NLST USA CT vs CR , Years Screen NELSON Ntherlnd CT vs Obs ITALUNG Italy CT vs Obs DLCST Denmark CT vs Obs MILD Italy CT vs Obs LUSI Germany CT vs Obs , , , , ,

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24 SCREENING CENTERS

25 Medically Fit

26 Methods Screening T0 T1 T2 Low dose CT scans acquired with use of multidetector scanners NLST radiologists reviewed studies and determined the outcome of the examination - positive vs negative result Results & recommendation s reported to participant and health care provider within 4 weeks of examination No standardized approach to the evaluation of nodules

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28 Screening Progression Screening Event Image Interpretation Management of Findings Evaluation and Treatment of Potential Cancer

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34 Lung Cancer Specific Mortality 356 vs 443 lung cancer deaths Relative reduction in the rate of death with low dose CT of 20% One death prevented per 320 screened

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40 Issues with Low Dose CT Screening False Positive Results- NLST- false positive rate 96.4 % Seven percent (7%) underwent invasive procedure (bronchoscopy) Risk of major complications NLST low ( 0.06%) Majority after surgery (14%) Futile detection of small aggressive tumors Futile detection of indolent disease lepidic pattern tumors Radiation exposure Increased cost/ Cost Benefit Balance? LDCT - $527 ( 2011 US Dollars) NCCN Individuals eligible screening in US 7 million Annual cost $ billion ( $12 billion/ year lung cancer US) NLST cost- effectiveness analysis - pending

41 Criticism regarding participants - NLST > 90 % of trial participants < 70 with 41% age < 60. Only 48 % were active smokers > 40% with higher levels of education = more motivated and not representative of rural populations Younger, more motivated urban population screened

42 Other methods of screening Biomarkers micro RNAs Aberrantly expressed in cancer Breath analysis Autoflourescence bronchoscopy (blue light bronchoscopy) and Narrow Band Imaging Rely on certain patterns of absorption by abnormal tissues Light emitted at specific wavelengths Useful in detecting pre-invasive endobronchial lesions Computer Aided Nodule Assessment and Risk Yield (CANARY) Management strategy

43 < 8 mm ACCP Guidelines 2013 Follow based on Fleischner Guidelines (2005) > 8 mm Determine Pretest Probability of Cancer Low ( < 5 %) Intermediate ( 5-65%) High ( > 65%)

44 Fleischner Guidelines (2005)

45 Determining the Probability of Malignancy Helps guide management of larger nodules Qualitative Evaluation Quantitative Evaluation Clinical Judgment Mathematical model Refer to Lung Nodule Clinic

46 Lung Nodule Clinics Why is there a need? Lack of use and adherence to guidelines Inconsistencies in published guidelines Varying expertise in physicians managing SPN Litigation? Potential Benefits Adoption of algorithms Multidisciplinary Team Thoracic Surgeon Pulmonologist Oncologist Radiologist

47 Management of Nodules

48 SUMMARY Low dose CT screening of select high risk patients reduces lung cancer specific mortality by 20% Majority of nodules identified in lung cancer screening (>90%) are benign Currently, ONLY patients identified by the NLST trial should undergo screening Only centers with multi-disciplinary coordinated care should provide lung cancer screening High Risk Lung Nodules are best evaluated in a multispecialty lung nodule clinic

49 Unanswered Questions What metrics should be developed to enhance the benefits and minimize the risks of screening? What is the most effective duration or frequency of screening? Role of primary prevention i.e. smoking cessation. Utility of biomarkers and other screening tools ( exhaled breath analysis) in lung cancer screening

50 References Reduced Lung Cancer Mortality with Low Dose Computed Tomographic Screening-NLST. NEJM 2011 Results of Initial Low-Dose Computed Tomographic Screening for Lung Cancer NEJM 2013 Results of the Two Incidence Screenings in the National Lung Screening Trial NEJM 2013 NCCN Clinical Practice Guidelines in Oncology- Lung Cancer Screening- Version 2014 Benefits and Harms of CT screening for lung cancer JAMA 2012 Screening for Lung Cancer CHEST 2013 Screening for Lung Cancer with Low Dose CT: A systematic review to update the US Preventive Services Task Force Recommendation. Ann Internal Med 2013 The National Lung Screening Trial: Overview and Study Design Radiology 2011