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Diagnosis and Management of LungCancer Executive Summary*ACCP Evidence-Based Clinical Practice Guidelines(2nd Edition)

W. Michael Alberts, MD, FCCP, Chair

(CHEST 2007; 132:1S–19S)

Key words: diagnosis; guidelines; lung cancer; management

Abbreviations: ACCP � American College of Chest Physicians; BAC � bronchioloalveolar carcinoma;CIS � carcinoma in situ; Dlco � diffusion capacity of the lung for carbon monoxide; EBUS-NA � endobronchialultrasound-needle aspiration; EUS-NA � endoscopic ultrasound-needle aspiration; FDG � fluorodeoxyglucose;NSCLC � non-small cell lung cancer; PET � positron emission tomography; PS � performance status; SCLC � smallcell lung cancer; SPN � solitary pulmonary nodule; SVC � superior vena cava; TBNA � transbronchial needleaspiration; TTNA � transthoracic needle aspiration

I n the 19th century, lung cancer was an unusualtumor; so much so that single case reports of the

rare cancer were published in the scientific literatureof the day. Things have changed. Other than skincancer, lung cancer is now the most common cancerand is the most frequent cause of death from cancerin both men and women.

In recognition of the importance of lung cancer inthe population and with the rise of evidence-basedmedicine as a basis for diagnosing the disease andmanaging those afflicted, in the year 2000 the Amer-ican College of Chest Physicians (ACCP), through itsHealth and Science Policy Committee, commis-sioned the development of evidence-based guide-lines on the diagnosis and management of lungcancer. The goal was to assist physicians in achievingthe best possible outcomes given the knowledge andcapabilities available at the time. The size of the task

was daunting, but the goal was laudable and theguidelines were successfully published as a Supple-ment to CHEST in January of 2003.

Fortunately, the pace of discovery in the diagnosisand management of lung cancer has quickened. As aresult, the ACCP found it prudent to commission thedevelopment of a second edition of the guidelines.This guideline Supplement is the result of that effortand represents the work of nearly 100 voluntaryfaculty and ACCP staff.

The methodology and grading system used todevelop the second edition of the guidelines may befound in a separate chapter. Rigorous adherence toformal guideline methodology was stressed. Thisattention to process detail and the use of the newlydeveloped ACCP grading system has produced avalid, yet clinically useful document.

In response to suggestions made after the firstedition, several new chapters have been added, such as“Diagnostic Surgical Pathology in Lung Cancer,”“Bronchioloalveolar Lung Cancer,” and “Complemen-tary Therapies and Integrative Oncology in Lung Can-cer.” A number of chapters have been extensivelyreworked to encompass recent knowledge; for exam-ple, “Screening for Lung Cancer, Management ofPatients with Pulmonary Nodules: When is it lungcancer?” (ie, the chapter previously termed the “Soli-tary Pulmonary Nodule”), “Bronchial Intraepithelial

*From H. Lee Moffitt Cancer Center and Research Institute,Tampa, FL.The author has no conflicts of interest to disclose.Manuscript received July 27, 2007; revision accepted July 30, 2007.Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: W. Michael Alberts, MD, MBA, FCCP, ChiefMedical Officer, H. Lee Moffitt Cancer Center and ResearchInstitute, Professor of Medicine, University of South FloridaCollege of Medicine, 12902 Magnolia Dr, Tampa, FL 33612;e-mail: [email protected]: 10.1378/chest.07-1860

CHEST SupplementDIAGNOSIS AND MANAGEMENT OF LUNG CANCER: ACCP GUIDELINES

www.chestjournal.org CHEST / 132 / 3 / SEPTEMBER, 2007 SUPPLEMENT 1S

Downloaded From: http://journal.publications.chestnet.org/ on 09/12/2013

Neoplasia/Early Central Airways Lung Cancer” (ie, thechapter previously termed “The Treatment of EarlyStage Non-small Cell Lung Cancer”), and “PalliativeCare Consultation,” “Quality of Life Measurement,”and “Bereavement for End-of-Life Care in Patientswith Lung Cancer.” All of the chapters have incorpo-rated information and knowledge gleaned from theliterature published since 2002.

Recommendations from each of the chapters arelisted below under their respective chapter titles.For an in-depth discussion or clarification of eachrecommendation, readers are encouraged to readthe specific chapter in question in its entirety.

Summary of Recommendations

Lung Cancer Chemoprevention

1. For individuals with a � 20–pack-yearhistory of smoking or with a history of lungcancer, the use of beta-carotene supple-mentation is not recommended for primary,secondary, or tertiary chemoprevention oflung cancer. Grade of recommendation, 1A

2. For individuals at risk for lung cancerand for patients with a history of lung can-cer, the use of vitamin E, retinoids, N-ace-tylcysteine, and aspirin is not recommendedfor primary, secondary, or tertiary preven-tion of lung cancer. Grade of recommenda-tion, 1A

3. For individuals at risk for lung canceror with a history of lung cancer, budeno-side, cyclooxygenase-2 inhibitors, 5-lipoxy-genase inhibitors, and prostaglandin ana-logs are not recommended for use forprimary, secondary, or tertiary lung cancerchemoprevention outside of the setting of awell-designed clinical trial. Grade of recom-mendation, 2C

4. In individuals at risk for lung cancer orwith a history of lung cancer, the use ofoltipraz as a primary, secondary, or tertiarychemopreventive agent of lung cancer isnot recommended. Grade of recommendation,1B

5. For individuals at risk for lung canceror with a history of lung cancer, the use ofselenium, and anethole dithiolethione, forprimary, secondary, or tertiary lung cancerchemoprevention is not recommended out-side of the setting of a well-designed clinicaltrial. Grade of recommendation, 1B

6. For individuals at risk for lung canceror with a history of lung cancer, there are notyet sufficient data to recommend the use ofany agent either alone or in combination forprimary, secondary, or tertiary lung cancerchemoprevention outside of a clinicaltrial. Grade of recommendation, 1B

Screening for Lung Cancer

1. We do not recommend that low-dosehelical CT be used to screen for lung cancerexcept in the context of a well-designedclinical trial. Grade of recommendation, 2C

2. We recommend against the use of se-rial chest radiographs to screen for thepresence of lung cancer. Grade of recommen-dations, 1A

3. We recommend against the use of sin-gle or serial sputum cytologic evaluation toscreen for the presence of lung cancer.Grade of recommendation, 1A

Diagnostic Surgical Pathology in Lung Cancer

1. When pathologically diagnosing lungcancer, the reporting of histologic type, tu-mor size and location, tumor grade (if appro-priate), lymphovascular invasion, involvementof pleura, surgical margins, and status andlocation of lymph nodes by station is recom-mended. Grade of recommendation, 1B

2. In individuals at risk for lung cancerbut without symptoms or history of cancer,utilization of single or serial sputum cyto-logic examinations to screen for the pres-ence of lung cancer is of insufficient clinicalbenefit and is not recommended. Grade ofrecommendation, 1A

3. In individuals with pleural-based tu-mors, when distinguishing between pleuraladenocarcinoma and malignant mesotheli-oma, a structured approach utilizing a lim-ited panel of histochemical and immunohis-tochemical assays is recommended toincrease the diagnostic accuracy. More chal-lenging cases may need additional studies,including ultrastructural analysis. Grade of rec-ommendation, 1B

4. In individuals with parenchymal-basedtumors, distinguishing between small cellcarcinoma and non-small cell carcinoma ofthe lung is recommended. For challengingcases, a diagnostic panel of immunohisto-chemical assays is recommended to increase

2S Diagnosis and Management of Lung Cancer: ACCP Guidelines


diagnostic accuracy. More challenging casesmay need additional studies, including ultra-structural analysis. Grade of recommendation, 1B

5. For individuals with glandular produc-ing tumors, distinguishing pure bronchi-oloalveolar carcinoma (BAC) from adenocar-cinoma with or without BAC component isrecommended. Grade of recommendation, 1C

6. For individuals with lung tumors whosedifferential includes primary lung carci-noma vs metastatic carcinoma, a directedpanel of immunohistochemical assays is rec-ommended to increase the diagnostic accu-racy. Grade of recommendation, 1C

7. For individuals with lung tumors whohave had an assessment of pathologic fea-tures and staging parameters, the evalua-tion of pathobiological and molecularmarkers is appropriate for protocol investi-gations and is not routinely recommendedfor clinical management. Grade of recom-mendation, 1C

8. For individuals with lung tumors whohave had an assessment of pathologic fea-tures and staging parameters, the determi-nation of occult or micrometastatic disease,utilizing enhanced pathologic or moleculartechniques, is not of sufficient clinical utilityand is not recommended. Grade of recommen-dation, 1C

Management of Patients With Pulmonary Nodules:When Is It Lung Cancer?

1. In every patient with a solitary pulmo-nary nodule (SPN), we recommend that cli-nicians estimate the pretest probability ofmalignancy either qualitatively by usingtheir clinical judgment or quantitatively byusing a validated model. Grade of recommen-dation, 1C

2. In every patient with an SPN that isvisible on chest radiography, we recom-mend that previous chest radiographs andother relevant imaging tests be reviewed.Grade of recommendation, 1C

3. In patients who have an SPN that showsclear evidence of growth on imaging tests,we recommend that tissue diagnosis shouldbe obtained unless specifically contraindi-cated. Grade of recommendation, 1C

4. In a patient with an SPN that is stable onimaging tests for at least 2 years, we suggestthat no additional diagnostic evaluation be

performed, except for patients with pureground-glass opacities on CT, for whom alonger duration of annual follow-up shouldbe considered. Grade of recommendation, 2C

5. In a patient with an SPN that is calci-fied in a clearly benign pattern, we recom-mend that no additional diagnostic evalua-tion is necessary. Grade of recommendation, 1C

6. In every patient with an indeterminateSPN that is visible on chest radiography, werecommend that CT of the chest should beperformed, preferably with thin sectionsthrough the nodule. Grade of recommenda-tion, 1C

7. In every patient with an indeterminateSPN that is visible on chest CT, we recom-mend that previous imaging tests should bereviewed. Grade of recommendation, 1C

8. In a patient with normal renal functionand an indeterminate SPN on chest radio-graph or chest CT, we recommend that CTwith dynamic contrast enhancement be con-sidered in centers with experience perform-ing this technique. Grade of recommendation, 1B

9. In patients with low-to-moderate pre-test probability of malignancy (5 to 60%)and an indeterminate SPN that measures atleast 8 to 10 mm in diameter, we recom-mend that fluorodeoxyglucose (FDG)-positron emission tomography (PET) imag-ing should be performed to characterize thenodule. Grade of recommendation, 1B

10. In patients with an SPN that has ahigh pretest probability of malignancy(� 60%), or patients with a subcentimeternodule that measures � 8 to 10 mm indiameter, we suggest that FDG-PET not beperformed to characterize the nodule.Grade of recommendation, 2C

11. In every patient with a SPN, we recom-mend that clinicians discuss the risks andbenefits of alternative management strategiesand elicit patient preferences. Grade of recom-mendation, 1C

12. In patients with an indeterminate SPNthat measures at least 8 to 10 mm indiameterand who are candidates for curative treat-ment, observation with serial

CT scans is an acceptable managementstrategy in the following circumstances:• When the clinical probability of malig-

nancy is very low (� 5%)



• When clinical probability is low (� 30 to40%) and the lesion is not hypermetabolicby FDG-PET or does not enhance � 15Hounsfield units on dynamic contrast CT

• When needle biopsy is nondiagnostic and thelesion is not hypermetabolic by FDG-PET

• When a fully informed patient prefers thisnonaggressive management approach.

Grade of recommendation, 2C13. In patients with an indeterminate

SPN that measures at least 8 to 10 mm indiameter who undergo observation, we sug-gest that serial CT scans be repeated at leastat 3, 6, 12, and 24 months. Grade of recom-mendation, 2C

14. In patients with an indeterminateSPN that measures at least 8 to 10 mm indiameter and who are candidates for cur-ative treatment, it is appropriate to per-form transthoracic needle biopsy or bron-choscopy in the following circumstances:• When clinical pretest probability and find-

ings on imaging tests are discordant; forexample, when the pretest probability ofmalignancy is high and the lesion is nothypermetabolic by FDG-PET

• When a benign diagnosis requiring spe-cific medical treatment is suspected

• When a fully informed patient desiresproof of a malignant diagnosis prior tosurgery, especially when the risk of surgi-cal complications is high.In general, we suggest that transthoracic

needle biopsy be the first choice for patientswith peripheral nodules unless the proce-dure is contraindicated or the nodule isinaccessible. We suggest that bronchosco-pybe performed when an air bronchogramis present or in centers with expertise innewer guided techniques. Grade of recom-mendation, 2C

15. In surgical candidates with an inde-terminate SPN that measures at least 8 to 10mm in diameter, surgical diagnosis is pre-ferred in most circumstances, including:• When the clinical probability of malig-

nancy is moderate to high (� 60%)• When the nodule is hypermetabolic by

FDG-PET imaging• When a fully informed patient prefers un-

dergoing a definitive diagnostic procedure.Grade of recommendation, 1C

16. In patients with an indeterminateSPN in the peripheral third of the lung whochose surgery, we recommend that thora-coscopy be performed to obtain a diagnosticwedge resection. Grade of recommendation, 1C

17. In a patient who chooses surgery withan indeterminate SPN that is not accessible bythoracoscopy, bronchoscopy, or transthoracicneedle aspiration (TTNA), we recommendthat a diagnostic thoracotomy should be per-formed. Grade of recommendation, 1C

18. In patients with a SPN who undergothoracoscopic wedge resection that is foundto be cancer by frozen section, we recom-mend that anatomic resection with system-atic mediastinal lymph node sampling ordissection be performed during the sameanesthetic. Grade of recommendation, 1C

19. In patients with an SPN who arejudged to be marginal candidates for lobec-tomy, we recommend definitive treatmentby wedge resection/segmentectomy (withsystematic lymph node sampling or dissec-tion). Grade of recommendation, 1B

20. For the patient with an SPN who is nota surgical candidate and who prefers treat-ment, we recommend that the diagnosis oflung cancer be confirmed by biopsy, unlesscontraindicated. Grade of recommendation, 1C

21. For the patient with a malignant SPNwho is not a surgical candidate and whoprefers treatment, we recommend referralfor external beam radiation or to a clinicaltrial of an experimental treatment such asstereotactic radiosurgery or radiofrequencyablation. Grade of recommendation, 2C

22. For surgical candidates with subcenti-meter nodules who have no risk factors forlung cancer, the frequency and duration offollow-up (preferably with low-dose CT)should depend on the size of the nodule. Wesuggest that:• Nodules measuring up to 4 mm in diame-

ter need not be followed up, but thepatient must be fully informed of the risksand benefits of this approach

• Nodules measuring � 4 to 6 mm should bere-evaluated at 12 months without the needfor additional follow-up if unchanged

• Nodules measuring � 6 to 8 mm should befollowed up sometime between 6 monthsand 12 months, and then again between



18 months and 24 months if unchanged.Grade of recommendation, 2C

23. For surgical candidates with subcenti-meter nodules who have one or more riskfactors for lung cancer, the frequency andduration of follow-up (preferably with low-dose CT) should depend on the size of thenodule. We suggest that:• Nodules measuring up to 4 mm in diame-

ter should be re-evaluated at 12 monthswithout the need for additional follow-upif unchanged

• Nodules measuring � 4 to 6 mm should befollowed up sometime between 6 monthsand 12 months, and then again between18 months and 24 months if unchanged

• Nodules measuring � 6 to 8 mm should befollowed up initially sometime between 3months and 6 months and then subse-quently between 9 months and 12 months,and again at 24 months if unchanged.

Grade of recommendation, 2C24. For surgical candidates with subcenti-

meter nodules that display unequivocal ev-idence of growth during follow-up, we rec-ommend that definitive tissue diagnosisshould be obtained, either by surgical resec-tion, transthoracic needle biopsy, or bron-choscopy. Grade of recommendation, 1C

25. For individuals with subcentimeternodules who are not candidates for curativetreatment, we recommend limited follow-up(in 12 months) or follow-up when symptomsdevelop. Grade of recommendation, 1C

26. In patients who are candidates forcurative treatment with a dominant SPNand one or more additional small nodules,we recommend that each nodule be evalu-ated individually, as necessary, and curativetreatment should not be denied unless thereis histopathologic confirmation of metasta-sis. Grade of recommendation, 1C

27. In surgical candidates with a solitarypulmonary metastasis, we recommend thatpulmonary metastasectomy be performed ifthere is no evidence of extrapulmonary ma-lignancy and there is no better available treat-ment. Grade of recommendation, 1C

28. In surgical candidates with an SPNthat has been diagnosed as small cell lungcancer (SCLC), we recommend surgical re-section with adjuvant chemotherapy, pro-vided that noninvasive and invasive stagingexclude the presence of regional or distantmetastasis. Grade of recommendation, 1C

29. In patients with an SPN in whomSCLC is diagnosed intraoperatively, we rec-ommend anatomic resection (with system-atic mediastinal lymph node sampling ordissection) under the same anesthetic ifthere is no evidence of nodal involvementand if the patient will tolerate resection.Surgery should be followed by adjuvantchemotherapy. Grade of recommendation, 1C

Initial Diagnosis of Lung Cancer

1. In patients suspected of having SCLCbased on radiographic and clinical findings,it is recommended that the diagnosis beconfirmed by the easiest method (sputumcytology, thoracentesis, fine-needle aspirate,bronchoscopy including transbronchial nee-dle aspiration [TBNA] and endobronchial ul-trasound-needle aspiration [EBUS-NA],endoscopic ultrasound-needle aspiration[EUS-NA]), as dictated by the patient’s pre-sentation. Grade of recommendation, 1C

2. In patients suspected of having lungcancer who have an accessible pleural effu-sion, thoracentesis is recommended to diag-nose the cause of the pleural effusion. Gradeof recommendation, 1C

3. In a patients suspected of having lungcancer who have an accessible pleural effu-sion, if pleural fluid cytology is negative(after at least two thoracenteses), thoracos-copy is recommended as the next step ifestablishing the cause of the pleural effu-sion is believed to be clinically important.Grade of recommendation, 1C

4. In patients suspected of having lungcancer who have a solitary extrathoracic sitesuspicious for metastasis, it is recommendedthat tissue confirmation of the metastaticsite be obtained if a fine-needle aspirate orbiopsy of the site are feasible. Grade ofrecommendation, 1C

5. In patients suspected of having lung can-cer who have lesions in multiple distant sitessuspected of metastases but in whom biopsyof a metastatic site would be technically diffi-cult, it is recommended that diagnosis of theprimary lung lesion be obtained by the easiestmethod (sputum cytology, bronchoscopy withTBNA or EBUS-NA, EUS-NA, or TTNA).Grade of recommendation, 1C

6. In patients suspected of having lungcancer who have extensive infiltration of themediastinum based on radiographic studies,



it is recommended that the diagnosis of lungcancer be established by the easiest andsafest method (bronchoscopy with TBNA,EBUS-NA, EUS-NA, TTNA, or mediastinos-copy). Grade of recommendation, 1C

7. In patients suspected of having lungcancer who present with a central lesionwith or without radiographic evidence ofmetastatic disease, in whom a semiinvasiveprocedure such as bronchoscopy or TTNAmight pose a higher risk, sputum cytology isrecommended as an acceptable method ofestablishing the diagnosis. However, thesensitivity of sputum cytology varies by lo-cation of the lung cancer. It is recom-mended that further testing be performedwith a nondiagnostic sputum cytology ifsuspicion of lung cancer remains. Grade ofrecommendation, 1C

8. In patients suspected of having lungcancer who have a central lesion, bronchos-copy is recommended to confirm the diag-nosis. However, it is recommended thatfurther testing be performed if bronchos-copy results are nondiagnostic and suspi-cion of lung cancer remains. Grade of recom-mendation, 1C

9. In expert hands, radial probe ultrasounddevise can increase the diagnostic yield offlexible bronchoscopy while dealing with pe-ripheral lesions � 20 mm in size. Its use canbe considered prior to referring the pa-tient for TTNA. Grade of recommendation, 2B

10. In patients suspected of having lungcancer who have a small (� 2 cm) periph-eral lesion, and who require tissue diagnosisbefore further management can beplanned, TTNA is recommended. However,it is recommended that further testing beperformed if TTNA results are nondiagnos-tic and suspicion of lung cancer remains.Grade of recommendation, 1B

11. In a patient suspected of having lungcancer, the diagnosis of non-small cell lungcancer (NSCLC) made on cytology (sputum,TTNA, or bronchoscopic specimens) ishighly reliable and can be accepted with ahigh degree of certainty. Grade of recommen-dation, 1B

12. The possibility of an erroneous diag-nosis of SCLC on a cytology specimen mustbe kept in mind if the clinical presentationor clinical course is not consistent with that ofSCLC. In such a case, it is recommended that

further testing (biopsy for histologic evalu-ation) be performed to establish a definitivecell type. Grade of recommendation, 1B

Initial Evaluation of the Patient With LungCancer: Symptoms, Signs, Laboratory Tests andParaneoplastic Syndromes

1. It is recommended that patients withknown or suspected lung cancer receivetimely and efficient care. Grade of recom-mendation, 1B

2. It is recommended that all patients withknown or suspected lung cancer have a thor-ough history, physical examination, and stan-dard laboratory tests as a screen for meta-static disease. Grade of recommendation, 1C

3. It is recommended that patients withlung cancer and a paraneoplastic syndromenot be precluded from potentially curativetherapy on the basis of these symptomsalone. Grade of recommendation, 2C

Physiologic Evaluation of the Patient WithSuspected Lung Cancer Being Considered forResection Surgery

1. It is recommended that patients withlung cancer be assessed for curative surgi-cal resection by a multidisciplinary team,which includes a thoracic surgeon specializ-ing in lung cancer, medical oncologist, radi-ation oncologist, and pulmonologist. Gradeof recommendation, 1C

2. It is recommended that patients withlung cancer not be denied lung resectionsurgery on the grounds of age alone. Gradeof recommendation, 1B

3. It is recommended that patients withlung cancer being evaluated for surgerywho have major factors for increased peri-operative cardiovascular risk undergo apreoperative cardiologic evaluation. Gradeof recommendation, 1C

4. In patients being considered for lungcancer resection, spirometry is recom-mended. If the FEV1 is � 80% of predictednormal or � 2 L and there is no evidence ofeither undue dyspnea on exertion or inter-stitial lung disease, the patient is suitablefor resection including pneumonectomywithout further physiologic evaluation. Ifthe FEV1 is � 1.5 L and there is no evidenceof either undue dyspnea on exertion orinterstitial lung disease, the patient is suit-



able for a lobectomy without further physio-logic evaluation. Grade of recommendation, 1C

5. In patients being considered for lungcancer resection, if there is evidence of eitherundue dyspnea on exertion or interstitial lungdisease, even though the FEV1 might be ade-quate, measuring diffusion capacity of thelung for carbon monoxide (DLCO) is recom-mended. Grade of recommendation, 1C

6. In patients being considered for lungcancer resection, if either the FEV1 or DLCO

are � 80% of predicted, it is recommendedthat postoperative lung function be pre-dicted through additional testing. Grade ofrecommendation, 1C

7. In patients with lung cancer being con-sidered for surgery, either a percentage ofpredicted postoperative FEV1 � 40% or apercentage of predicted postoperativeDLCO � 40% indicate an increased risk forperioperative death and cardiopulmonarycomplications with standard lung resection.It is recommended that these patients un-dergo exercise testing preoperatively. Gradeof recommendation, 1C

8. In patients with lung cancer being con-sidered for surgery, either a product ofpercentage of predicted postoperativeFEV1 and percentage of predicted postop-erative DLCO � 1,650 or a percentage ofpredicted postoperative FEV1 � 30% indi-cate an increased risk for perioperativedeath and cardiopulmonary complicationswith standard lung resection. It is recom-mended that these patients be counseled-about nonstandard surgery and nonopera-tive treatment options for their lung cancer.Grade of recommendation, 1C

9. In patients with lung cancer being con-sidered for surgery, a maximum oxygenuptake � 10 mL/kg/min indicates an in-creased risk for perioperative death andcardiopulmonary complications with stan-dard lung resection. These patients shouldbe counseled about nonstandard surgeryand nonoperative treatment options fortheir lung cancer. Grade of recommendation, 1C

10. Patients with lung cancer being con-sidered for surgery who have a maximumoxygen uptake � 15 mL/kg/min and both apercentage of predicted postoperativeFEV1 and DLCO � 40 are at increased riskfor perioperative death and cardiopulmo-

nary complications with standard lung resec-tion. It is recommended that these patients becounseled about nonstandard surgery andnonoperative treatment options for their lungcancer. Grade of recommendation, 1C

11. Patients with lung cancer being con-sidered for surgery who walk � 25 shuttleson two shuttle walks or less than one flight ofstairs are at increased risk for perioperativedeath and cardiopulmonary complicationswith standard lung resection. These patientsshould be counseled about nonstandard sur-gery and nonoperative treatment options fortheir lung cancer. Grade of recommendation, 1C

12. In patients with lung cancer beingconsidered for surgery, a PaCO2 � 45 mmHg is not an independent risk factor forincreased perioperative complications.However, it is recommended that these pa-tients undergo further physiologic testing.Grade of recommendation, 1C

13. In patients with lung cancer beingconsidered for surgery, an arterial oxygensaturation � 90% indicates an increasedrisk for perioperative complications withstandard lung resection. It is recommendedthat these patients undergo further physio-logic testing. Grade of recommendation, 1C

14. In patients with very poor lung func-tion and lung cancer in an area of upper-lobe emphysema, it is recommended thatcombined lung volume reduction surgeryand lung cancer resection be considered ifboth the FEV1 and DLCO are � 20% ofpredicted. Grade of recommendation, 1C

15. It is recommended that all patients withlung cancer be counseled regarding smokingcessation. Grade of recommendation, 1C

Noninvasive Staging of NSCLC

1. For patients with either a known orsuspected lung cancer who are eligible fortreatment, a CT scan of the chest withcontrast including the upper abdomen(liver and adrenal glands) should be per-formed. Grade of recommendation, 1B

2. In patients with enlarged discrete me-diastinal lymph nodes on CT (� 1 cm inshort axis) and no evidence of metastaticdisease, further evaluation of the mediasti-num should be made prior to definitivetreatment of the primary tumor. Grade ofrecommendation, 1B



3. PET to evaluate for mediastinal andextrathoracic staging should be consideredin patients with clinical 1A lung cancerbeing treated with curative intent. Grade ofrecommendation, 2C

4. Patients with clinical IB-IIIB lung can-cer being treated with curative intentshould undergo PET (where available) formediastinal and extrathoracic staging.Grade of recommendation, 1B

5. In patients with an abnormal result onFDG-PET, further evaluation of the medi-astinum with sampling of the abnormallymph node should be performed prior tosurgical resection of the primary tumor.Grade of recommendation, 1B

6. For patients with either known or sus-pected lung cancer who are eligible for treat-ment, MRI of the chest should not routinelybe performed for staging the mediastinum.MRI may be useful in patients with NSCLCwhen there is concern for involvement of thesuperior sulcus or brachial plexus involve-ment. Grade of recommendation, 1B

7. For patients with either known or sus-pected lung cancer, a thorough clinical eval-uation similar to that listed in Table 4 in thischapter should be performed. Grade of rec-ommendation, 1B

8. Patients with abnormal clinical evalua-tions should undergo imaging for extratho-racic metastases. Site-specific symptoms war-rant directed evaluation of that site with themost appropriate study (eg, head CT/MRIplus either whole-body PET or bone scan plusabdominal CT). Grade of recommendation, 1B

9. Routine imaging for extrathoracic me-tastases (eg, head CT/MRI plus eitherwhole-body PET or bone scan plus abdom-inal CT) should be performed in patientswith clinical stage IIIA and IIIB disease(even if they have a negative clinical evalu-ation). Grade of recommendation, 2C

10. Patients with imaging studies consistentwith distant metastases should not be ex-cluded from potentially curative treatmentwithout tissue confirmation or overwhelmingclinical and radiographic evidence of metas-tases. Grade of recommendation, 1B

Invasive Mediastinal Staging of Lung Cancer

1. For patients with extensive mediastinalinfiltration of tumor (and no distant metas-tases), radiographic (CT) assessment of themediastinal stage is usually sufficient with-out invasive confirmation. Grade of recom-mendation, 2C

2. For patients with discrete mediastinallymph node enlargement (and no distantmetastases), invasive confirmation of theradiographic stage is recommended (re-gardless of whether a PET finding is posi-tive or negative in the mediastinal nodes).Grade of recommendation, 1B

3. For patients with discrete mediastinallymph node enlargement (and no distantmetastases), many invasive techniques forconfirmation of the N2,3 node status aresuggested as reasonable approaches (medi-astinoscopy, EUS-NA, TBNA, EBUS-NA,TTNA), given the appropriate experienceand skill. Grade of recommendation, 1B

4. For patients with discrete mediastinallymph node enlargement (and no distantmetastases), a nonmalignant result from aneedle technique (EUS-NA, TBNA, EBUS-NA, TTNA) should be further confirmed bymediastinoscopy (regardless of whether aPET finding is positive or negative in themediastinal nodes). Grade of recommenda-tion, 1C

5. For patients with a radiographicallynormal mediastinum (by CT) and a centraltumor or N1 lymph node enlargement(andno distant metastases), invasive confir-mation of the radiographic stage is recom-mended (regardless of whether a PET findingis positive or negative in the mediastinalnodes). Grade of recommendation, 1C

6. For patients with a central tumor or N1lymph node enlargement (and no distantmetastases), invasive staging is recom-mended. In general, mediastinoscopy issuggested, but EUS-NA or EBUS-NA maybe a reasonable alternative if nondiagnosticresults are followed by mediastinoscopy.Grade of recommendation, 2C

7. For patients with a peripheral clinicalstage I tumor in whom a PET scan showsuptake in mediastinal nodes (and not distantmetastases), invasive staging is recom-



mended. In general, mediastinoscopy issuggested, but EUS-NA or EBUS-NA maybe a reasonable alternative if nondiagnosticresults are followed by mediastinoscopy.Grade of recommendation, 1C

8. For patients with a peripheral clinicalstage I tumor, invasive confirmation of themediastinal nodes is not needed if a PETscan result is negative in the mediastinum.Grade of recommendation, 1C

9. For the patients with a left upper lobecancer in whom invasive mediastinal stag-ing is indicated as defined by the previousrecommendations, it is suggested that in-vasive mediastinal staging include assess-ment of the aortopulmonary windownodes (via Chamberlain, thoracoscopy, ex-tended cervical mediastinoscopy, EUS-NAor EBUS-NA) if other mediastinal nodestations are found to be uninvolved. Gradeof recommendation, 2C

Bronchial Intraepithelial Neoplasia/EarlyCentral Airways Lung Cancer

1. For patients with severe dysplasia,carcinoma in situ (CIS), or carcinoma insputum cytology but with chest imagingstudies showing no localizing abnormality,standard white light bronchoscopy is rec-ommended. Autofluorescence bronchos-copy should be used when available. Gradeof recommendation, 1B

2. For patients being considered forcurative endobronchial therapy to treatCIS in centers where it is available,autofluorescent bronchoscopy may beconsidered to guide therapy. Grade of rec-ommendation, 2C

3. For patients with known severe dyspla-sia or CIS in the central airways, standardwhite light bronchoscopy is recommendedat periodic intervals (3 to 6 months) forfollow-up. Autofluorescence bronchoscopyshould be used when available. Grade ofrecommendation, 2C

4. For patients with superficial squamouscell carcinoma who are not surgical candi-dates, photodynamic therapy, electrocau-tery, cryotherapy, and brachytherapy arerecommended as treatment options. Use ofNd:YAG laser therapy is not recommendedbecause of the risk of perforation. Grade ofrecommendation, 1C

Treatment of NSCLC Stage I and II

1. For patients with clinical stage I and IINSCLC and no medical contraindication tooperative intervention, surgical resection isrecommended. Grade of recommendation, 1A

2. For patients with clinical stage I and IINSCLC, it is recommended that they be eval-uated by a thoracic surgical oncologist with aprominent part of his/her practice focused onlung cancer, even if the patients are beingconsidered for nonsurgical therapies such aspercutaneous ablation or stereotactic bodyradiation therapy. Grade of recommendation, 1B

3. In patients with stage I and II NSCLCwho are medically fit for conventional sur-gical resection, lobectomy or greater resec-tion are recommended rather than sublobarresections (wedge or segmentectomy).Grade of recommendation, 1A

4. In patients with stage I NSCLC whomay tolerate operative intervention but nota lobar or greater lung resection due tocomorbid disease or decreased pulmonaryfunction, sublobar resection is recom-mended over nonsurgical interventions.Grade of recommendation, 1B

5. In patients with stage I NSCLC whoare considered appropriate candidates forthoracoscopic anatomic lung resection (lo-bectomy or segmentectomy), the use ofvideo-assisted thoracic surgery by sur-geons experienced in these techniques isan acceptable alternative to open thora-cotomy. Grade of recommendation, 1B

6. In patients undergoing resection forstage I and II NSCLC, it is recommendedthat intraoperative systematic mediastinallymph node sampling or dissection be per-formed for accurate pathologic staging.Grade of recommendation, 1B

7. For patients with centrally or locallyadvanced NSCLC in whom a complete re-section can be achieved with either tech-nique, sleeve lobectomy is recommendedover pneumonectomy. Grade of recommenda-tion, 1B

8. For patients with N1 lymph node me-tastases (stage II NSCLC) in whom a com-plete resection can be achieved with eithertechnique, sleeve lobectomy is recom-mended over pneumonectomy. Grade of rec-ommendation, 1B



9. For patients with completely resectedstage IA NSCLC, the use of adjuvant che-motherapy is not recommended for routineuse outside the setting of a clinical trial.Grade of recommendation, 1A

10. For patients with completely resectedstage IB NSCLC, the use of adjuvant che-motherapy is not recommended for routineuse. Grade of recommendation, 1B

11. For patients with completely resectedstage II NSCLC and good performance sta-tus (PS), the use of platinum-based adju-vant chemotherapy is recommended.Grade of recommendation, 1A

12. For patients with stage I or II NSCLCwho are not candidates for surgery (“medi-cally inoperable”) or who refuse surgery,curative intent fractionated radiotherapy isrecommended. Grade of recommendation, 1B

13. For patients with completely resectedstage IA or IB NSCLC, postoperative radio-therapy is associated with a decreased sur-vival and is not recommended. Grade ofrecommendation, 1B

14. For patients with completely resectedstage II NSCLC, postoperative radiother-apy decreases local recurrence but a sur-vival benefit has not been clearly shown,and therefore postoperative radiotherapy isnot recommended. Grade of recommendation,1B

Treatment of NSCLC Stage IIIA: Incidental(Occult) N2 Disease Found at Thoracotomy(Stage IIIA1–2)

Surgical Considerations

1. In patients with NSCLC who have inci-dental (occult) N2 disease (IIIA2) found atsurgical resection and in whom completeresection of the lymph nodes and primarytumor is technically possible, completion ofthe planned lung resection and mediastinallymphadenectomy is recommended. Gradeof recommendation, 2C

2. In patients with NSCLC undergoingsurgical resection, systematic mediastinallymph node sampling or complete medias-tinal lymph node dissection is recom-mended. Grade of recommendation, 1B

Adjuvant Chemotherapy

3. In patients with resected NSCLC whowere found to have incidental (occult) N2

disease (IIIA1–2) and who have good PS,adjuvant platinum-based chemotherapy isrecommended. Grade of recommendation, 1A

Adjuvant Radiotherapy

4. In patients with resected NSCLC whowere found to have incidental (occult) N2disease (IIIA1–2), adjuvant postoperativeradiotherapy should be considered after ad-juvant chemotherapy to reduce local recur-rence. Grade of recommendation, 2C

Adjuvant Chemoradiotherapy

5. In patients with resected NSCLC whowere found to have incidental (occult) N2disease (IIIA1–2), combined postoperativeconcurrent chemotherapy and radiotherapyis not recommended except as part of aclinical trial. Grade of recommendation, 1B

Treatment of NSCLC Stage IIIA: PotentiallyResectable N2 Disease (Stage IIIA3)

6. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), referralfor multidisciplinary evaluation (which in-cludes a thoracic surgeon) is recom-mended before embarking on definitivetreatment. Grade of recommendation, 1C

7. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), induc-tion therapy followed by surgery is notrecommended except as part of a clinicaltrial. Grade of recommendation, 1C

8. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3) who do re-ceive induction chemoradiotherapy as partof a clinical trial, pneumonectomy is notrecommended. The subsequent surgical re-section in this setting should be limited to alobectomy. If after induction chemoradio-therapy it appears that a pneumonectomy willbe needed, it is recommended that pneumo-nectomy not be performed and treatmentshould be continued with full-dose radiother-apy. Grade of recommendation, 1B

9. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), primarysurgical resection followed by adjuvanttherapy is not recommended except as partof a clinical trial. Grade of recommendation,1C



10. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), surgeryalone is not recommended. Grade of recom-mendation, 1A

11. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), platinum-based combination chemoradiotherapy is rec-ommended as primary treatment. Grade ofrecommendation, 1B

Surgical Considerations

12. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3), surgical de-bulking procedures are not recommended.Grade of recommendation, 1A

13. In NSCLC patients with N2 diseaseidentified preoperatively (IIIA3) who haveincomplete resections, postoperative plati-num-based chemoradiotherapy is recom-mended. Grade of recommendation, 1C

Treatment of NSCLC Stage IIIA: Unresectable,Bulky N2 Disease (Stage IIIA4)

14. In patients with NSCLC who havebulky N2 disease (IIIA4) and good PS,radiotherapy alone is not recommended.Grade of recommendation, 1A

15. In patients with NSCLC who havebulky N2 disease (IIIA4) and good PS, combi-nation platinum-based chemotherapy and ra-diotherapy are recommended. Grade of rec-ommendation, 1A

16. In patients with NSCLC who havebulky N2 disease (IIIA4), good PS, andminimal weight loss, concurrent chemora-diotherapy is recommended over sequen-tial chemoradiotherapy. Grade of recom-mendation, 1A

Treatment of NSCLC Stage IIIB

1. In selected patients with clinicalT4N0-1 NSCLC due to satellite tumor nod-ule(s) in the same lobe, carinal involvement,or superior vena cava (SVC) invasion, it isrecommended that evaluation be per-formed by a multidisciplinary team thatincludes a thoracic surgeon with lung can-cer expertise to determine if the patient isoperable. Surgery is not recommended ifthere is N2 involvement. Grade of Recom-mendation, 1C

2. For patients with stage IIIB NSCLCdue to N3 disease, treatment with neoadju-

vant (induction) chemotherapy or chemora-diotherapy followed by surgery is not rec-ommended. Grade of recommendation, 1C

3. For patients with stage IIIB diseasewithout malignant pleural effusions, PS of 0or 1, and minimal weight loss (< 5%), plat-inum-based combination chemotherapy isrecommended. Grade of recommendation, 1A

4. In patients with stage IIIB NSCLC andPS of 2 or those with substantial weight loss(� 10%), chemoradiotherapy is recom-mended only after careful consideration.Grade of recommendation, 1C

5. For stage IIIB NSCLC patients with PSof 0 or 1 and minimal weight loss (< 5%),concurrent chemoradiotherapy is recom-mended. Grade of recommendation, 1A

6. The most efficacious chemotherapydrugs to be combined with thoracic radio-therapy and the number of cycles of chemo-therapy needed to yield the best results iscurrently uncertain. No one combination che-motherapy regimen can be recommended.Grade of recommendation, 2C

7. For patients with stage IIIB NSCLC,once-daily thoracic radiotherapy plus che-motherapy is recommended. Grade of recom-mendation, 1B

8. For stage IIIB patients and either poorPS or disease too extensive to treat with cur-ative intent and symptoms due to chest dis-ease, palliative radiotherapy is recom-mended. The fractionation pattern should bechosen based on the physician’s judgment andpatient’s needs. Grade of recommendation, 1A

Treatment of NSCLC Stage IV

1. In patients with stage IV NSCLC and agood PS, two-drug combination chemother-apy is recommended. The addition of athird cytotoxic chemotherapeutic agent isnot recommended because it provides nosurvival benefit and may be harmful. Gradeof recommendation, 1A

2. Bevacizumab improves survival com-bined with carboplatin and paclitaxel in aclinically selected subset of the good PS,stage IV NSCLC (nonsquamous histology,lack of brain metastases, and no hemopty-sis). In these patients, bevacizumab addedto carboplatin and paclitaxel should be con-sidered a therapeutic option. Grade of rec-ommendation, 1A



3. In patients with stage IV NSCLC whoare elderly (> 70 to 79 years) single-agentchemotherapy is recommended for mostpatients. Grade of recommendation, 1A

4. However, in patients with stage IVNSCLC who are elderly (> 70 to 79 years)and have a good PS and lack significantcomorbidities, two-drug combination che-motherapy is recommended as an option.Grade of recommendation, 1B

5. In patients with stage IV NSCLC whoare > 80 years old, the benefit of chemo-therapy is unclear and should be decided onbased on individual circumstances. Grade ofrecommendation, 2C

6. In patients with stage IV NSCLC and aPS of 2, chemotherapy is recommendedbased on defined response rates and symp-tom palliation. Grade of recommendation, 1B

7. In patients with stage IV NSCLC and aPS of 2, no specific recommendation can begiven with regard to the optimal chemo-therapeutic strategy. A single phase III trialshowed a survival benefit to a carboplatin-based doublet compared to a single agent ina prospectively planned subset analysis.Grade of recommendation, 2C

8. It is recommended that patient-re-ported health-related quality of life be mea-sured using the FACT-L or European Orga-nization for Research and Treatment ofCancer QLQ-C30 questionnaire because itis a significant prognostic factor for survival.Grade of recommendation, 1A

9. It is recommended that patients withstage IV NSCLC receive adequate educa-tion about the risks and benefits of chemo-therapy to enable active participation in thedecision-making process regarding treat-ment selection. Grade of recommendation, 1C

Special Treatment Issues in Lung Cancer

1. In patients with a Pancoast tumor, it isrecommended that a tissue diagnosis beobtained prior to the initiation of therapy.Grade of recommendation, 1C

2. In patients with a Pancoast tumor beingconsidered for curative intent surgical re-section, an MRI of the thoracic inlet andbrachial plexus to rule out tumor invasion ofunresectable vascular structures or the ex-tradural space is recommended. Grade ofrecommendation, 1C

3. In patients with a Pancoast tumorinvolving the subclavian vessels or verte-bral column, it is suggested that resectionbe undertaken only at a specialized cen-ter. Grade of recommendation, 2C

4. In patients with a Pancoast tumor beingconsidered for curative resection, invasivemediastinal staging and extrathoracic imag-ing (head CT/MRI plus either whole-bodyPET or abdominal CT plus bone scan) isrecommended. Involvement of mediastinalnodes and/or metastatic disease represent acontraindication to resection. Grade of rec-ommendation, 1C

5. In patients with a potentially resect-able, nonmetastatic Pancoast tumor (andgood PS), it is recommended that preoper-ative concurrent chemoradiotherapy be ad-ministered prior to resection. Grade of rec-ommendation, 1B

6. In patients undergoing resection of aPancoast tumor, it is recommended thatevery effort be made to achieve a completeresection. Grade of recommendation, 1A

7. It is recommended that resection of aPancoast tumor consist of lobectomy (in-stead of a nonanatomic wedge resection) aswell as the involved chest wall structures.Grade of recommendation, 1C

8. In patients with either a completely orincompletely resected Pancoast tumor,postoperative radiotherapy is not recom-mended because of lack of demonstratedsurvival benefit. Grade of recommendation, 2C

9. In patients with an unresectable, butnonmetastatic Pancoast tumor who havegood PS, definitive concurrent chemother-apy and radiotherapy is recommended.Grade of recommendation, 1C

10. In patients with Pancoast tumors whoare not candidates for curative intent treat-ment, palliative radiotherapy is recom-mended. Grade of recommendation, 1B

11. In patients with a clinical T4N0,1M0NSCLC being considered for curative resec-tion, it is recommend that invasive mediasti-nal staging, and extrathoracic imaging (headCT/MRI plus either whole-body PET or ab-dominal CT plus bone scan) be undertaken.Involvement of mediastinal nodes and/or met-astatic disease represent a contraindication toresection. Grade of recommendation, 1C



12. In patients with a T4N0,1M0 NSCLC,it is recommended that resection be under-taken only at a specialized center. Grade ofrecommendation, 1C

13. In patients with suspected or provenlung cancer and a satellite nodule within thesame lobe, it is recommend that no furtherdiagnostic workup of a satellite nodule isundertaken. Grade of recommendation, 1B

14. In patients with a satellite lesionwithin the same lobe as a suspected orproven primary lung cancer, evaluation ofextrathoracic metastases and confirmationof the mediastinal node status should beperformed as dictated by the primary lungcancer alone, and not modified due to thepresence of the satellite lesion. Grade ofrecommendation, 1C

15. In patients with NSCLC and a satellitefocus of cancer within the same lobe (and nomediastinal or distant metastases), resectionvia a lobectomy is the recommended treat-ment. Grade of recommendation, 1B

16. In patients with two synchronous pri-mary NSCLCs being considered for cura-tive surgical resection, invasive mediastinalstaging and extrathoracic imaging (headCT/MRI plus either whole-body PET orabdominal CT plus bone scan) are recom-mended. Involvement of mediastinal nodesand/or metastatic disease represent a con-traindication to resection. Grade of recom-mendation, 1C

17. In patients suspected of having twosynchronous primary NSCLCs, a thoroughsearch for an extrathoracic primary cancerto rule out the possibility that both of thelung lesions represent metastases is recom-mended. Grade of recommendation, 1C

18. In patients not suspected of having asecond focus of cancer who are found intra-operatively to have a second cancer in adifferent lobe, resection of each lesion is rec-ommended, provided the patient has ade-quate pulmonary reserve and there is no N2nodal involvement. Grade of recommendation,1C

19. In patients with a metachronousNSCLC being considered for curative surgi-cal resection, invasive mediastinal staging andextrathoracic imaging (head CT/MRI plus ei-ther whole-body PET or abdominal CT plusbone scan) are recommended. Involvement of

mediastinal nodes and/or metastatic diseaserepresent a contraindication to resection.Grade of recommendation, 1C

20. In patients with an isolated brain me-tastasis from NSCLC being considered forcurative resection of a stage I or II lungprimary tumor, invasive mediastinal stagingand extrathoracic imaging (head CT/MRI pluseither whole-body PET or abdominal CT plusbone scan) are recommended. Involvement ofmediastinal nodes and/or metastatic diseaserepresent a contraindication to resection.Grade of recommendation, 1C

21. In patients with no other sites of metas-tases and a synchronous resectable N0,1 pri-mary NSCLC, resection or radiosurgical ab-lation of an isolated brain metastasis arerecommended (as well as resection of theprimary tumor). Grade of recommendation, 1C

22. In patients with no other sites ofmetastases and a previously completely re-sected primary NSCLC (metachronous pre-sentation), resection or radiosurgical abla-tion of an isolated brain metastasis isrecommended. Grade of recommendation, 1B

23. In patients who have undergone acurative resection of an isolated brain me-tastasis, adjuvant whole-brain radiotherapyis suggested, although there is conflictingand insufficient data regarding a benefitwith respect to survival or the rate of recur-rent brain metastases. Grade of recommenda-tion, 2B

24. In patients who have undergone cur-ative resections of both the isolated brainmetastasis and the primary tumor, adjuvantchemotherapy may be considered. Grade ofrecommendation, 2C

25. In patients with an isolated adrenalmetastasis from NSCLC being consideredfor curative intent surgical resection, inva-sive mediastinal staging, and extrathoracicimaging (head CT/MRI plus either whole-body PET or abdominal CT plus bone scan)are recommended. Involvement of medias-tinal nodes and/or metastatic disease repre-sent a contraindication to resection. Gradeof recommendation, 1C

26. In patients with a synchronous resect-able N0,1 primary NSCLC, with no othersites of metastases, resection of the primarytumor and an isolated adrenal metastasis isrecommended. Grade of recommendation, 1C



27. In patients with no other sites ofmetastases and a previously completely re-sected primary NSCLC (metachronous pre-sentation), resection of an isolated adrenalmetastasis is the recommended treatmentof choice if the disease-free interval is > 6months and complete resection of the pri-mary NSCLC has been achieved. Grade ofrecommendation, 1C

28. In patients with a NSCLC invadingthe chest wall who are being considered forcurative intent surgical resection, invasivemediastinal staging and extrathoracic imag-ing (head CT/MRI plus either whole-bodyPET or abdominal CT plus bone scan) arerecommended. Involvement of mediastinalnodes and/or metastatic disease represent acontraindication to resection, and definitivechemoradiotherapy is recommended forthese patients. Grade of recommendation, 2C

29. At the time of resection of a tumorinvading the chest wall, we recommend thatevery effort be made to achieve a completeresection. Grade of recommendation, 1B

BAC

1. We recommend the use of the termBAC be reserved for those lung cancers thatmeet the criteria established in the revisedWorld Health Organization classificationsystem for lung tumors. Grade of recommen-dation, 1B

2. For patients with suspected BAC, werecommend a surgical biopsy be used toestablish a histopathologic diagnosis.Grade of recommendation, 1C

3. For patients unable to undergo surgicalbiopsy, the diagnosis of BAC should be madeonly with compatible histopathologic patternon transbronchial or core needle biopsy, anda CT demonstrating a pure ground-glass orpneumonic appearance. Grade of recommenda-tion, 1C

4. For patients whose CT scans showground-glass attenuation or pneumonicconsolidation (suggesting BAC), PET scanresults are often false negative, and there-fore we recommend that a negative PETscan result be followed by additional diag-nostic testing to exclude the presence ofcancer. Grade of recommendation, 1C

5. In patients with suspected BAC whoare good surgical candidates, a sublobarresection may be appropriate, provided the

CT shows a pure ground-glass appearance,intraoperative pathologic consultation con-firms pure BAC without evidence of inva-sion, and surgical margins are free of dis-ease. Grade of recommendation, 1B

6. For patients with good PS and unresect-able BAC, we recommend the use of standardchemotherapy. The use of first-line epidermalgrowth factor receptor-targeted agents shouldbe reserved for patients with poor PS, or thoseenrolled in clinical trials. Grade of recommenda-tion, 2C

Management of SCLC

1. Routine staging of SCLC includes thefollowing: history and physical examination,CBC counts and comprehensive chemistrypanel, CT scan of the chest and abdomen orCT of the chest with cuts going through theentire liver and adrenal glands, CT or MRIof the brain, and bone scan. Grade of recom-mendation, 1B

2. PET scanning is not recommended inthe routine staging of SCLC. Grade of rec-ommendation, 2B

3. Patients with extensive-stage diseaseshould receive four to not more than six cyclesof cisplatin- or carboplatin-based combinationchemotherapy. Cisplatin could be combinedwith either etoposide or irinotecan. Grade ofrecommendation, 1B

4. After chemotherapy, patients achievinga complete response outside the chest and acomplete or partial response in the chestcould be offered consolidative thoracic ra-diation therapy in the chest. Grade of recom-mendation, 2C

5. Outside of a clinical trial, maintenancetreatment for patients with extensive-stage orlimited- stage disease achieving a partial orcomplete remission is not recommended.Grade of recommendation, 1B

6. Relapsed or refractory patients withSCLC should be offered further chemother-apy. Grade of recommendation, 1B

7. Elderly patients with good PS (EasternCooperative Oncology Group PS of 0 or 1)with intact organ function should be treatedwith platinum-based chemotherapy. Gradeof recommendation, 1A

8. Elderly patients with poor prognosticfactors such as poor PS or medically signif-icant concomitant comorbid disease may



still be considered for chemotherapy. Gradeof recommendation, 2C

9. Outside of a clinical trial, there is no rolefor either dose dense/intense initial/inductionor maintenance treatment for extensive-stage or limited-stage SCLC. Grade of recom-mendation, 1A

10. Patients with limited-stage SCLCshould be treated with combined concur-rent chemoradiotherapy. Patients requirereferral to a radiation oncologist and a med-ical oncologist for the consideration of com-bined modality treatment. Grade of recom-mendation, 1A

11. If the PS and comorbid illnesses allow,patients with limited-stage disease shouldbe treated with chemotherapy and radiationtherapy administered concurrently. Gradeof recommendation, 1C

12. In patients eligible to receive earlyconcurrent chemoradiotherapy, patientsshould be treated with accelerated hyperfrac-tionated radiation therapy concurrently withplatinum-based chemotherapy. Grade of rec-ommendation, 1B

13. Patients with limited-stage SCLCachieving a complete remission or resectedpatients with stage I disease should be of-fered PCI. Grade of recommendation, 1B

14. Patients with extensive stage SCLCachieving a complete remission shouldbe offered PCI. Grade of recommendation,1C

15. In patients with SCLC and stage Idisease who are being considered for cura-tive intent surgical resection, invasive medi-astinal staging and extrathoracic imaging(head CT/MRI, abdominal CT plus bonescan) followed by a platinum-based chemo-therapy should be offered. Grade of recom-mendation, 1A

16. In patients with stage I SCLC whohave undergone curative intent surgical re-section, platinum-based adjuvant chemo-therapy is recommended. Grade of recom-mendation, 2C

17. Patients with mixed SCLC/NSCLChistology should be treated the same aspatients with SCLC. All treatment recom-mendations made for SCLC should applyto this category of patients. Grade of rec-ommendation, 2C

Complementary Therapies and IntegrativeOncology in Lung Cancer

1. It is recommended that all patientswith lung cancer be specifically asked aboutthe use of complementary and alternativetherapies. Grade of recommendation, 1C

2. It is recommended that all patientswith lung cancer be given guidance aboutthe advantages and disadvantages of com-plementary therapies in an open, evi-dence-based, and patient- centered man-ner by a qualified professional. Grade ofrecommendation, 1C

3. In lung cancer patients, mind-body mo-dalities are recommended as part of a multi-modality approach to reduce anxiety, mooddisturbances, or chronic pain. Grade of recom-mendation, 1B

4. In lung cancer patients with anxiety orpain, massage therapy delivered by an on-cology-trained massage therapist is recom-mended as part of a multimodality treat-ment approach. Grade of recommendation, 1C

5. The application of deep or intensepressure is not recommended near cancerlesions or anatomic distortions, such aspostoperative changes, as well as in pa-tients with a bleeding tendency. Grade ofrecommendation, 2C

6. For lung cancer patients, therapiesbased on putative manipulation of bioen-ergy fields are not recommended. Grade ofrecommendation, 1C

7. Acupuncture is recommended as acomplementary therapy when pain is poorlycontrolled or when side effects, such asneuropathy or xerostomia from other mo-dalities, are clinically significant. Grade ofrecommendation, 1A

8. Acupuncture is recommended as a com-plementary therapy when nausea and vomit-ing associated with chemotherapy are poorlycontrolled. Grade of recommendation, 1B

9. Electrostimulation wristbands are notrecommended for managing chemothera-py- induced nausea and vomiting. Grade ofrecommendation, 1B

10. When the lung cancer patient doesnot stop smoking despite use of other op-tions, a trial of acupuncture is recom-mended to assist in smoking cessation.Grade of recommendation, 2C



11. In patients with lung cancer sufferingfrom symptoms such as dyspnea, fatigue,chemotherapy-induced neuropathy, orpostthoracotomy pain, a trial of acupunc-ture is recommended. Grade of recommenda-tion, 2C

12. In patients with a bleeding tendency,it is recommended that acupuncture be per-formed by qualified practitioners and usedcautiously. Grade of recommendation, 1C

13. It is recommended that dietary sup-plements, in particular herbal products, beevaluated for side effects and potential in-teraction with other drugs. Those that arelikely to interact with other drugs, such aschemotherapeutic agents, should not beused concurrently during chemotherapy orradiation, or prior to surgery. Grade of rec-ommendation, 1B

14. In lung cancer patients who either failor decline antitumor therapies, it is recom-mended use of botanical agents occur onlyin the context of clinical trials. Grade ofrecommendation, 1C

15. It is recommended that patients beadvised to avoid therapies promoted as “al-ternatives” to mainstream care. Grade ofrecommendation, 1A

Follow-up and Surveillance of the Lung CancerPatient Following Curative Intent Therapy

1. In lung cancer patients treated withcurative intent therapy, follow-up for com-plications related to the curative intenttherapy should be managed by the appro-priate specialist and should probably last atleast 3 to 6 months. At that point, the patientshould be reevaluated by the multidisci-plinary tumor board for entry into an ap-propriate surveillance program for detect-ing recurrences and/or metachronoustumors. Grade of recommendation, 2C

2. In lung cancer patients treated withcurative intent therapy, and those havingadequate performance and pulmonaryfunctions, surveillance with a history, phys-ical examination, and imaging study (eitherchest radiography or CT) is recommendedevery 6 months for 2 years and then annually.All patients should be counseled on symptomrecognition and be advised to contact theirphysician if worrisome symptoms were recog-nized. Grade of recommendation, 1C

3. Ideally, surveillance for recognition ofa recurrence of the original lung cancerand/or development of a metachronous tu-mor should be coordinated through a mul-tidisciplinary team approach. If possible,the physician who diagnosed the primarylung cancer and initiated the curative intenttherapy should remain as the health-careprovider overseeing the surveillance pro-cess. Grade of recommendation, 2C

4. In lung cancer patients following cura-tive intent therapy, use of blood tests, PETscanning, sputum cytology, tumor markers,and fluorescence bronchoscopy is not cur-rently recommended for surveillance. Gradeof recommendation, 2C

5. Lung cancer patients who smoke shouldbe strongly encouraged to stop smoking, andoffered pharmacotherapeutic and behavioraltherapy, including follow-up. Grade of recom-mendation, 1A

Palliative Care in Lung Cancer

1. All lung cancer patients and their fam-ilies must be reassured that pain can berelieved safely and effectively. All patientsshould be questioned regularly about theirpain, using the patient’s self-report of painand a simple rating scale as the primarysource of assessment. Grade of recommenda-tion, 1A

2. For all patients, individualize medica-tions that are used to control pain. Admin-ister medications regularly, and treat painappropriately. Document the effectivenessof pain management at regular intervals dur-ing treatment. Grade of recommendation, 1A

3. For all patients with mild-to-moder-ate pain, manage the pain initially withacetaminophen or an nonsteroidal antiin-flammatory drug, assuming there are nocontraindications to their use. Use opioidswhen pain is more severe or when itincreases. Grade of recommendation, 1B

4. For any patient, if it is anticipated thatthere will be a continuous need for opioidmedication, meperidine is not recom-mended. It has a short duration of action,and its metabolite normeperidine is toxicand can cause CNS stimulation resulting indysphoria, agitation, and seizures. Grade ofrecommendation, 1B



5. For patients whose pain is not con-trolled by pure analgesic medications, ad-junctive medications such as tricyclicantidepressants, anticonvulsants, and neu-roleptic agents will often augment the ef-fects of pure analgesic medications. Grade ofrecommendation, 1C

6. For all patients, administer medica-tions by mouth because of convenienceand cost- effectiveness. In patients withlung cancer who cannot take pain medica-tions by mouth, rectal and transdermal ad-ministration are recommended. Administra-tion of analgesics by the IM route is notrecommended because of pain, inconve-nience, and unreliable absorption. Grade ofrecommendation, 1C

7. For all patients receiving opioids, be-cause constipation is common anticipate it,treat it prophylactically, and constantlymonitor it. Grade of recommendation, 1B

8. Encourage all patients to remain activeand to care for themselves whenever possi-ble. Avoid prolonged immobilization when-ever possible. Grade of recommendation, 1B

9. In patients who have pain associatedwith muscle tension and spasm, it is recom-mended that complimentary methods forpain relief such as cutaneous stimulationtechniques (heat and cold applications),acupuncture, psychosocial methods of care,and pastoral care be incorporated into thepain management plan, but not as a substitutefor analgesics. Grade of recommendation, 1C

10. For patients with advanced lung can-cer, provide palliative radiation therapy tocontrol pain. Palliative chemotherapy to de-crease pain and other symptoms is recom-mended, even though the increase in sur-vival may be only modest. Grade ofrecommendation, 1B

11. In patients with lung cancer who havepain unresponsive to standard methods ofpain control, referral to a specialized painclinic or palliative care consultant is recom-mended. Grade of recommendation, 1C

12. For all lung cancer patients who com-plain of dyspnea, it is recommended thatthey be evaluated for potentially correct-able causes, such as localized obstruction ofa major airway, a large pleural effusion,pulmonary emboli, or an exacerbation ofcoexisting COPD or congestive heart falure.If one of these problems is identified, treat-

ment with appropriate methods is recom-mended. Grade of recommendation, 1C

13. For all lung cancer patients whose dys-pnea does not have a treatable cause, opioidsare recommended. Also recommended areother pharmacologic approaches such as oxy-gen, bronchodilators, and corticosteroids.Grade of recommendation, 1C

14. For all lung cancer patients with dys-pnea, it is recommended that nonpharma-cologic and noninterventional treatmentsbe considered, such as patient and familyeducation, breathing control, activity pac-ing, relaxation techniques, fans, and psycho-social support. Grade of recommendation, 2C

15. For all lung cancer patients who havetroublesome cough, it is recommended thatthey be evaluated for treatable causes.Grade of recommendation, 1B

16. For all lung cancer patients who havetroublesome cough without a treatablecause, it is recommended that opioids beused to suppress the cough. Grade of recom-mendation, 1B

17. For patients with lung cancer whohave pain due to bone metastases, externalradiation therapy is recommended for painrelief. A single fraction of 8 Gy is as effectiveas higher fractionated doses of external ra-diation therapy for immediate relief of pain.Grade of recommendation, 1A

18. For patients with lung cancer whohave pain due to bone metastases, higherfractionated doses of radiation therapy pro-vide a longer duration of pain relief, lessfrequent need for retreatment, and fewerskeletal-related events than does a singlefraction. Grade of recommendation, 1A

19. For patients with lung cancer whohave painful bone metastases, bisphospho-nates are recommended together with ex-ternal radiation therapy for pain relief.Grade of recommendation, 1A

20. For patients with lung cancer whohave painful bone metastases refractory toanalgesics, radiation, and bisphosphonates,radiopharmaceuticals are recommendedfor pain relief. Grade of recommendation, 1B

21. In patients with lung cancer who havepainful bone metastases to long bones and/orweight-bearing bones and a solitary well-de-fined lytic lesion circumferentially involving� 50% of the cortex and an expected survival� 4 weeks with satisfactory health status,



surgical fixation is recommended to mini-mize the potential for a fracture. Intramed-ullary nailing is the preferred approach,especially for the femur or the humerus.Grade of recommendation, 1C

22. In patients with lung cancer who havesymptomatic brain metastases, dexametha-sone at 16 mg/d is recommended during thecourse of definitive therapy with a rapidtaper and discontinuation within 6 weeks ofcompletion of definitive therapy (either sur-gery or radiation therapy). Grade of recom-mendation, 1B

23. Patients with NSCLC and an isolatedsolitary brain metastasis should be consid-ered for a curative resection of the lungprimary tumor, as long as a careful searchfor other distant metastases or mediastinallymph nodes has been performed and resultsare negative. Grade of recommendation, 1C

24. In patients with no other sites ofmetastases and a synchronous resectableN0,1 primary NSCLC, resection or radio-surgical ablation of an isolated brain metas-tasis should be undertaken (as well as resec-tion of the primary tumor). Resection of theisolated solitary brain metastases should befollowed by whole-brain radiotherapy.Grade of recommendation, 1B

25. For cancer patients with lung cancerwho have new onset of back pain, sagittalT1-weighted MRI of the entire spine isrecommended for diagnostic purposes. Otherdiagnostic studies such as plain radiographs,bone scans, or CT myelograms are not recom-mended. Grade of recommendation, 1C

26. For patients with lung cancer andepidural spinal cord metastases who are notparetic and ambulatory, prompt treatmentwith high-dose dexamethasone and radio-therapy is recommended. Grade of recom-mendation, 1B

27. When there is symptomatic radio-graphically confirmed compression of thespinal cord, neurosurgical consultationmust be sought and, if appropriate, sur-gery should be performed immediatelyand should then be followed by radiationfor patients with metastatic epidural spi-nal cord compression and generally goodPS. Grade of recommendation, 1A

28. For all lung cancer patients with large-volume hemoptysis, bronchoscopy is recom-mended to identify the source of bleeding,

followed by endobronchial management op-tions such as argon plasma coagulators, Nd-YAG laser, and electrocautery. Grade of rec-ommendation, 1C

29. In lung cancer patients with symptom-atic malignant pleural effusions, thoracen-tesis is recommended as the first drainageprocedure for symptom relief. Grade of rec-ommendation, 1C

30. In lung cancer patients with symp-tomatic pleural effusions that recur afterthoracentesis, chest tube drainage andpleurodesis are recommended. Grade ofrecommendation, 1B

31. In patients with SVC obstruction fromsuspected lung cancer, definitive diagnosis byhistologic or cytologic methods is recom-mended before treatment is started. Gradeof recommendation, 1C

32. In patients with symptomatic SVCobstruction due to SCLC, chemotherapy isrecommended. Grade of recommendation, 1C

33. In patients with symptomatic SVCobstruction due to NSCLC, stent insertionand/or radiation therapy are recommended.Stents are also recommended for SCLC orNSCLC symptomatic patients with SVC ob-struction who do not respond to chemother-apy or radiation therapy. Grade of recom-mendation, 1C

34. For patients with a malignant tracheo-esophageal or bronchoesophageal fistula,stenting of esophagus, airway, or bothshould be considered for symptomatic re-lief. Attempts at curative resection oresophageal bypass of the involved airwayand/or the esophagus are not recom-mended. Grade of recommendation, 1C

35. It is recommended that all patientswith lung cancer be evaluated for the pres-ence of depression and, if present, treatedappropriately. Grade of recommendation, 1C

Palliative Care Consultation, Quality of LifeMeasurements, and Bereavement for End-of-LifeCare in Patients With Lung Cancer

1. For all patients with advanced lungcancer (and their families), it is recom-mended that palliative care be integratedinto their treatment, including those pur-suing curative or life-prolonging thera-pies. Grade of recommendation, 1C



2. For patients with advanced lung can-cer, it is recommended that palliative andend-of-life care include involvement of apalliative care consultation team, whichshould be made available. Grade of recom-mendation, 1C

3. For patients with advanced lung can-cer, it is recommended that standardizedevaluations with symptom assessment andabbreviated disease-specific health-re-lated quality-of-life questionnaires shouldbe administered by the responsible mem-ber of the health-care team at the appro-priate frequency. Grade of recommenda-tion, 1B

4. It is recommended that clinicians ofpatients who die from lung cancer extendcommunication with the bereaved familyand friends after death. Grade of recommen-dation, 1C

5. For patients with lung cancer, proac-tive interventions, such as those listed be-low, are recommended to improve griefoutcomes:a. Informing the patient and family of fore-

seeable death within weeksb. Forewarning family of impending deathc. Enabling effective palliative care, fo-

cused on spiritual, existential, physical,and practical concerns.

Grade of recommendation, 1C6. It is recommended that clinicians of

dying patients with lung cancer encouragecaregivers to maintain a healthy lifestyleduring the period of caregiver burden, aswell as during bereavement. Grade of recom-mendation, 1C

7. It is recommended that clinicians ofpatients dying from lung cancer honor ritualsof death and mourning in a culturally sensi-tive manner. Grade of recommendation, 1C



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