Non–Small Cell Lung Cancer, Version 2.2013

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

Abstract

These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

NCCN: Continuing Education

Accreditation Statement

This activity has been designated to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.

This activity is accredited for 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.

National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-13-011-H01-P

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 70% minimum passing score and complete the evaluation at http://education.nccn.org/node/22017; and 4) view/print certificate.

Release date: June 10, 2013; Expiration date: June 10, 2014

Learning Objectives:

Upon completion of this activity, participants will be able to:

  • Integrate into professional practice the updates to NCCN Guidelines for NSCLC.

  • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for NSCLC.

F1NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 6; 10.6004/jnccn.2013.0084

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Overview

Smoking tobacco is the primary risk factor for lung cancer.1-4 The risk of lung cancer increases with the number of packs of cigarettes smoked per day and the number of years spent smoking (ie, pack-years of smoking history).5-7 Thus, current smokers should be encouraged to quit (http://www.smokefree.gov/),1,8-11 and former smokers should be encouraged to avoid smoking. Agents that can be used to promote smoking cessation include nicotine replacement (eg, gum, inhaler, lozenge, nasal spray, patch), sustained-release bupropion, and varenicline (http://www.ahrq.gov/clinic/tobacco/medsmoktab.htm).8-11 Other risk factors for lung cancer include radon, disease history, family history of lung cancer, and occupational exposure (eg, asbestos, silica, coal smoke, and diesel fumes; see the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Lung Cancer Screening, available online at NCCN.org).1,4,12,13

F2NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 6; 10.6004/jnccn.2013.0084

Currently, most patients with lung cancer are diagnosed at an advanced stage when curative treatment is not possible. Thus, lung cancer has a higher mortality rate than other types of cancer. Only 15.9% of all patients with lung cancer are alive 5 years or more after diagnosis.14 In 2013, an estimated 228,000 new diagnoses and 159,500 deaths from lung and bronchial cancer will occur in the United States.15 Screening with low-dose CT has been shown to decrease the mortality rate from lung cancer.16 Although screening with low-dose CT can be used to identify possible lung cancer, most cases are currently identified through other means (eg, symptoms, including weight loss, long-term cough, dyspnea), because lung cancer screening is not yet widely available and many insurance companies are not currently paying for screening. Early-stage lung cancer is often detected in patients because a chest radiograph or CT scan (obtained for other reasons) incidentally shows a lung nodule or mass. For patients with suspected lung cancer, diagnostic and treatment strategies should be decided in a multidisciplinary setting and on an individual basis to maximize outcomes.

Data show that low-dose CT can be used to detect lung cancer at an early stage when it is more likely curable.16 The NCCN Guidelines for Lung Cancer Screening recommend screening with low-dose CT for select high-risk current and former smokers without symptoms of lung cancer17 (to view the most recent version of these guidelines, visit NCCN.org). Other organizations also recommend screening with low-dose CT for select high-risk patients (eg, American College of Chest Physicians, American Cancer Society, American Lung Association, ASCO, and American Thoracic Society) (http://www.lung.org/lungdisease/lungcancer/lungcancerscreeningguidelines/).18-20

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) discuss management of non-squamous NSCLC (eg, adenocarcinoma), which is the most common type of lung cancer, and also less

F3NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 6; 10.6004/jnccn.2013.0084

common types of lung cancer (eg, squamous cell carcinoma, large cell carcinoma).21 Other types of thoracic cancer are discussed in the NCCN Guidelines for Malignant Pleural Mesothelioma, Small Cell Lung Cancer, and Thymomas and Thymic Carcinomas (to view the most recent version of these guidelines, visit NCCN.org).

Principles of Diagnostic Evaluation

A new section on diagnostic evaluation of suspected lung cancer was added for the 2013 update (see DIAG-A, pages 649 and 650). This new section includes an algorithm for evaluating suspicious lung nodules observed on chest radiograph or CT scan (see DIAG-1 and DIAG-2, page 647 and 648).

Diagnostic Evaluation of Lung Nodules

This new diagnostic section describes the evaluation of suspicious pulmonary nodules or masses that are seen on chest radiograph and CT. Patient factors (eg, age, smoking history, occupational exposure) and radiologic characteristics (eg, nodule size, shape, other lung pathology) must be carefully evaluated by a multidisciplinary diagnostic team to help formulate decisions about how to proceed with the workup of a suspicious lung nodule. The NCCN Guidelines recommend biopsy or surgical excision for highly suspicious nodules or further surveillance for nodules with a low suspicion of cancer, depending on the type of nodule and a multidisciplinary evaluation of other patient factors (see DIAG-1, page 647). PET/CT scans also may be used to aid the decision-making process. Several factors, including the size of the pulmonary nodule, whether the nodule is changing in size, and the type of nodule (eg, solid noncalcified nodule vs nonsolid nodule), are used to determine whether the nodule is more or less likely to be lung cancer (see DIAG-2, page 648).22-25

Diagnostic Evaluation of Suspected Lung Cancer

The diagnostic strategy benefits from a multidisciplinary

F4NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 6; 10.6004/jnccn.2013.0084

evaluation that includes thoracic radiologists, thoracic surgeons, and pulmonary physicians. The NCCN Guidelines recommend that the diagnostic strategy be individualized for each patient depending on the size and location of the tumor or nodule, the presence of mediastinal or distant disease, patient characteristics (eg, comorbidities), and local experience. Decisions regarding whether a biopsy (including what type of biopsy) or surgical excision is appropriate depend on several factors, as outlined in the NCCN algorithm (see DIAG-A, pages 649 and 650). In many situations when the suspicion of lung cancer is high and the patient is a surgical candidate, preoperative biopsy may be unnecessary, because it adds time, cost, and procedural risk but is unlikely to alter the plan for surgical resection (ie, pathologic diagnosis is established intraoperatively). However, if an intraoperative diagnosis is risky or difficult or if there is a significant suspicion of an alternative diagnosis, then a preoperative biopsy may be beneficial.

The optimal biopsy approach depends on various factors, including size and location of the nodule, associated lung disease (eg, emphysema), proximity to other structures, and experience and technologies available in the local health care system. Factors to be considered in choosing a biopsy technique include diagnostic yield (sensitivity), diagnostic accuracy (especially true-negative yield), adequacy of tissue volume, risk of the procedure, efficiency (access and timeliness of biopsy), and local experience and expertise. In general, the least-invasive biopsy technique with the highest diagnostic yield should be selected, and the NCCN Guidelines outline general principles to help direct clinicians in this process (see DIAG-A, pages 649 and 650). Radial probe endobronchial ultrasound (EBUS), navigational bronchoscopy, or transthoracic needle aspiration is recommended for patients with suspected peripheral nodules.26-32 Routine bronchoscopy

F5NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

Version 2.2013 © National Comprehensive Cancer Network, Inc. 2013, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 11, 6; 10.6004/jnccn.2013.0084

with (or without) EBUS is preferable for centrally located masses. Mediastinoscopy, EBUS, or navigational bronchoscopy is recommended for patients with suspected nodal disease.33,34 Another general principle is to preferentially biopsy the abnormality that would simultaneously confer the highest tumor stage. For example, in a patient with a suspicious liver lesion or pleural effusion, liver biopsy or thoracentesis would most efficiently obtain a tissue diagnosis and establish stage IV disease. Communication among the pathologist, medical oncologist, and practitioner performing the biopsy is of the utmost importance to ensure that sufficient tissue is obtained and processed properly to facilitate molecular testing for genetic alterations (eg, epidermal growth factor receptor mutations, ALK gene rearrangements).

If pathology results from biopsy or surgical excision indicate a diagnosis of NSCLC (see Principles of Pathologic Review in the NCCN Guidelines for NSCLC; to view the complete version of these guidelines, visit NCCN.org), then further evaluation and clinical staging must be performed so that the patient's health care team can determine the most appropriate and effective treatment plan (see NSCL-1, above). Accurate histology must be determined (eg, adenocarcinoma, squamous cell carcinoma) before initiating systemic therapy; a general diagnosis of NSCLC is not recommended.21 Diagnosis, staging, and planned resection (eg, lobectomy) are ideally a single operative procedure for patients with early-stage disease (see DIAG-A, pages 649 and 650). Confirmation and staging of lung cancer are essential before lobectomy or pneumonectomy, although they can be performed with intraoperative diagnosis and concomitant mediastinal staging. The mediastinal lymph nodes must be assessed, because upstaging can occur in patients with presumed early-stage NSCLC based on imaging alone.34-36

Conclusions

Most patients with lung cancer are currently identified by symptoms, including weight loss, long-term cough, and dyspnea. For patients with suspected lung cancer, diagnostic and treatment strategies should be decided in a multidisciplinary setting and on an individual basis to maximize outcomes. A new section on diagnostic evaluation of suspected lung cancer was added for the 2013 update of the NCCN Guidelines for NSCLC (to view the most recent version of these guidelines, visit NCCN.org). This new diagnostic section describes the evaluation of suspicious pulmonary nodules or masses that are seen on chest radiograph and CT. Patient factors and radiologic characteristics must be carefully evaluated by a multidisciplinary diagnostic team to help formulate decisions about how to proceed with workup of a suspicious lung nodule. The NCCN Guidelines recommend that the diagnostic strategy be individualized for each patient depending on the size and location of the tumor, the presence of mediastinal or distant disease, patient characteristics, and local experience. The least-invasive biopsy technique with the highest diagnostic yield should be selected; the NCCN Guidelines outline general principles for this process. When obtaining a biopsy specimen, it is essential that the pathologist, medical oncologist, and practitioner confer to ensure that sufficient tissue is obtained and processed properly to facilitate molecular testing. If NSCLC is diagnosed, then further evaluation and clinical staging must be performed so that the patient's health care team can determine the most appropriate and effective treatment plan.

EDITOR: Kerrin M. Green, MA, Assistant Managing Editor, JNCCN—Journal of the National Comprehensive Cancer Network, has disclosed that she has no relevant financial relationships.

CE AUTHORS: Nicole B. Harrold, BS, Manager, Continuing Education and Grants, has disclosed that she has no relevant financial relationships. Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, has disclosed that she has no relevant financial relationships. James Prazak, RPh, Assistant Director, Continuing Education and Grants, has disclosed the following relationships with commercial interests: Bristol-Myers Squibb Company: Pension; Pfizer, Inc: Stockholder; United Healthcare Group: Stockholder; Johnson & Johnson: Stockholder. Miranda Hughes, PhD, Oncology Scientist/Senior Medical Writer, has disclosed that she has no relevant financial relationships.

References

  • 1

    de GrootPMundenRF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am2012;50:863-876.

  • 2

    AlbergAJFordJGSametJM. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines. 2nd ed.Chest2007;132:29S-55S.

  • 3

    Dela CruzCSTanoueLTMatthayRA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med2011;32:605-644.

  • 4

    SecretanBStraifKBaanR. A review of human carcinogens—part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol2009;10:1033-1034.

    • Search Google Scholar
    • Export Citation
  • 5

    JhaPRamasundarahettigeCLandsmanV. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med2013;368:341-350.

    • Search Google Scholar
    • Export Citation
  • 6

    ThunMJCarterBDFeskanichD. 50-year trends in smoking-related mortality in the United States. N Engl J Med2013;368:351-364.

  • 7

    DollRPetoR. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J1976;2:1525-1536.

  • 8

    HaysJTMcFaddenDDEbbertJO. Pharmacologic agents for tobacco dependence treatment: 2011 update. Curr Atheroscler Rep2012;14:85-92.

  • 9

    RigottiNA. Strategies to help a smoker who is struggling to quit. JAMA2012;308:1573-1580.

  • 10

    FioreMCBakerTB. Clinical practice. Treating smokers in the health care setting. N Engl J Med2011;365:1222-1231.

  • 11

    HurtRDEbbertJOHaysJTMcFaddenDD. Preventing lung cancer by treating tobacco dependence. Clin Chest Med2011;32:645-657.

  • 12

    StraifKBenbrahim-TallaaLBaanR. A review of human carcinogens—part C: metals, arsenic, dusts, and fibres. Lancet Oncol2009;10:453-454.

    • Search Google Scholar
    • Export Citation
  • 13

    BaanRGrosseYStraifK. A review of human carcinogens—Part F: chemical agents and related occupations. Lancet Oncol2009;10:1143-1144.

  • 14

    HowladerNNooneAKrapchoM. SEER Cancer Statistics Review 1975-2009 (Vintage 2009 Populations) based on November 2011 SEER data submission. Bethesda, MD: National Cancer Institute; 2012. Available at: http://seer.cancer.gov/csr/1975_2009_pops09/.

    • Search Google Scholar
    • Export Citation
  • 15

    SiegelRNaishadhamDJemalA. Cancer statistics, 2013. CA Cancer J Clin2013;63:11-30.

  • 16

    AberleDRAdamsAMBergCD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med2011;365:395-409.

  • 17

    WoodDEEapenGAEttingerDS. Lung cancer screening. J Natl Compr Canc Netw2012;10:240-265.

  • 18

    WenderRFonthamETBarreraEJr. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin2013;63:107-117.

  • 19

    JaklitschMTJacobsonFLAustinJH. The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg2012;144:33-38.

    • Search Google Scholar
    • Export Citation
  • 20

    BachPBMirkinJNOliverTK. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA2012;307:2418-2429.

  • 21

    TravisWDBrambillaENoguchiM. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol2011;6:244-285.

    • Search Google Scholar
    • Export Citation
  • 22

    ArmatoSG3rdMcLennanGBidautL. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI): a completed reference database of lung nodules on CT scans. Med Phys2011;38:915-931.

    • Search Google Scholar
    • Export Citation
  • 23

    MacMahonHAustinJHGamsuG. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology2005;237:395-400.

    • Search Google Scholar
    • Export Citation
  • 24

    NaidichDPBankierAAMacmahonH. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology2013;266:304-317.

    • Search Google Scholar
    • Export Citation
  • 25

    GodoyMCNaidichDP. Overview and strategic management of subsolid pulmonary nodules. J Thorac Imaging2012;27:240-248.

  • 26

    YasufukuKNakajimaTFujiwaraT. Role of endobronchial ultrasound-guided transbronchial needle aspiration in the management of lung cancer. Gen Thorac Cardiovasc Surg2008;56:268-276.

    • Search Google Scholar
    • Export Citation
  • 27

    JensenKWHsiaDWSeijoLM. Multicenter experience with electromagnetic navigation bronchoscopy for the diagnosis of pulmonary nodules. J Bronchology Interv Pulmonol2012;19:195-199.

    • Search Google Scholar
    • Export Citation
  • 28

    ChaoTYChienMTLieCH. Endobronchial ultrasonography-guided transbronchial needle aspiration increases the diagnostic yield of peripheral pulmonary lesions: a randomized trial. Chest2009;136:229-236.

    • Search Google Scholar
    • Export Citation
  • 29

    PaoneGNicastriELucantoniG. Endobronchial ultrasound-driven biopsy in the diagnosis of peripheral lung lesions. Chest2005;128:3551-3557.

    • Search Google Scholar
    • Export Citation
  • 30

    Du RandIABarberPVGoldringJ. Summary of the British Thoracic Society guidelines for advanced diagnostic and therapeutic flexible bronchoscopy in adults. Thorax2011;66:1014-1015.

    • Search Google Scholar
    • Export Citation
  • 31

    LeongSJuHMarshallH. Electromagnetic navigation bronchoscopy: a descriptive analysis. J Thorac Dis2012;4:173-185.

  • 32

    HsiaDWJensenKWCurran-EverettDMusaniAI. Diagnosis of lung nodules with peripheral/radial endobronchial ultrasound guided transbronchial biopsy. J Bronchology Interv Pulmonol2012;19:5-11.

    • Search Google Scholar
    • Export Citation
  • 33

    RintoulRCTournoyKGEl DalyH. EBUS-TBNA for the clarification of PET positive intra-thoracic lymph nodes-an international multi-centre experience. J Thorac Oncol2009;4:44-48.

    • Search Google Scholar
    • Export Citation
  • 34

    DefranchiSAEdellESDanielsCE. Mediastinoscopy in patients with lung cancer and negative endobronchial ultrasound guided needle aspiration. Ann Thorac Surg2010;90:1753-1757.

    • Search Google Scholar
    • Export Citation
  • 35

    YasufukuKPierreADarlingG. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg2011;142:1393-1400.e1.

    • Search Google Scholar
    • Export Citation
  • 36

    BilleAPelosiESkanjetiA. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg2009;36:440-445.

    • Search Google Scholar
    • Export Citation

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    NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2013

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