. 2014 Aug;60(8):e395–e404.

Table 2.

Summary of guideline recommendations, literature review, and supporting evidence

GUIDELINE OR REVIEW	*SUMMARY OF RECOMMENDATIONS, LITERATURE REVIEW, OR SUPPORTING EVIDENCE (RATING OR LEVEL OF EVIDENCE^†‡§)**
Factors that increase the risk of lung cancer
• NICE,⁹ 2005	Recommendations (C): current or former smokers; smoking-related COPD; previous exposure to asbestos; previous history of cancer (especially head and neck)
• NICE,⁹ 2005	Summary of literature review (additional risk factors reported): occupational exposure to dust or microscopic particles (eg, wood dust, silica); past medical history of COPD; silicosis or tuberculosis; family history of cancer; exposure to known carcinogens (eg, radon, chromium, nickel)
• NZGG,¹⁰ 2009	Cited NICE 2005 recommendations and literature review
• SIGN,¹⁸ 2005	Recommendations: current or former smokers, especially those older than 40 y; COPD
• SIGN,¹⁸ 2005	Supporting evidence: cited a study that showed 22% of patients diagnosed with lung cancer had coexistent COPD
• ACCP (Kvale,¹⁵ 2006)	Summary of literature review: tobacco smoking; passive cigarette smoke exposure; asbestos, radon, and exposure to selected other carcinogens; COPD; family history of lung cancer

Symptoms and signs that raise suspicion of lung cancer and require further investigation
• NICE,⁹ 2005	Recommendations: Hemoptysis (D) Any of the following unexplained persistent symptoms and signs lasting more than 3 wk (D) or sooner if patients have higher risk of lung cancer (C): chest or shoulder pain; dyspnea; weight loss; chest signs; hoarseness; finger clubbing; dysphagia; cervical or supraclavicular lymphadenopathy; cough with or without any of the above; features suggestive of metastasis from a lung cancer (eg, in brain, bone, liver, or skin) Unexplained changes in existing symptoms in patients with underlying chronic respiratory problems (D) Individuals with a history of asbestos exposure and recent onset of chest pain, shortness of breath, or unexplained systemic symptoms (C)
• NZGG,¹⁰ 2009	Recommendations (C): Unexplained hemoptysis Any of the following unexplained persistent (lasting more than 3 wk or less than 3 wk in people with known risk factors) symptoms and signs: chest or shoulder pain; shortness of breath; weight loss, loss of appetite; abnormal chest signs; hoarseness; finger clubbing; cervical or supraclavicular lymphadenopathy; cough; features suggestive of metastasis from lung cancer (eg, in brain, bone, liver, or skin) Summary of literature review (additional factors reported): dysphagia; fever; pneumonia; superior vena cava obstruction; weakness; wheezing
• SIGN,¹⁸ 2005	Recommendations: Unexplained or persistent hemoptysis (D) Any of the following symptoms persisting for more than 3 wk without an obvious cause: cough; chest or shoulder pain; dyspnea; weight loss; chest signs; hoarseness; finger clubbing; features suggestive of metastases from lung cancer (eg, brain, bone, liver, or skin); persistent cervical or supraclavicular lymphadenopathy (D) Patients with COPD who develop new symptoms (especially weight loss) that might be attributable to lung cancer (√)
• ACCP (Kvale,¹⁵ 2006) and ACCP (Spiro et al,⁴ 2007)	Summary of literature review: Initial symptoms or signs of lung cancer, in order of most to least frequent, included cough; weight loss; dyspnea; chest pain; hemoptysis; bone pain; clubbing; fever; weakness; superior vena cava obstruction; dysphagia; and wheezing and stridor⁴ Provided list of symptoms and signs associated with systemic metastases and paraneoplastic syndromes associated with lung cancer⁴ Supporting evidence: Reported that paraneoplastic syndromes might occur in 10% of patients with lung cancer⁴ Cough is present > 65% patients diagnosed with lung cancer¹⁵ Dyspnea often accompanies cough associated with lung cancer¹⁵

Recommended initial investigation of suspicious lung cancer symptoms
• NICE,⁹ 2005	Recommendation: A chest x-ray scan is the principal diagnostic investigation for lung cancer in primary care (D)
• NZGG,¹⁰ 2009	Recommendation: Urgent chest x-ray scan is recommended in patients presenting with symptoms and signs raising suspicion of lung cancer (C)
• SIGN,¹⁸ 2005	Recommendation: A chest x-ray scan should be performed on all patients being investigated for the possibility of lung cancer (D) Supporting evidence: Partly based on study of 345 patients that showed normal chest x-ray scan findings were seen in only 2% of lung cancer patients; patients with lung cancer often have obstructive features (37%) and pleural effusions (22%)
• ACCP (Spiro et al,⁴ 2007)	Provided laboratory tests that would be useful in evaluating patients for metastatic or paraneoplastic syndromes associated with lung cancer⁴

Recommendations for the use of chest CT scans in the investigation of suspected lung cancer
• SIGN,¹⁸ 2005	Recommendations: Contrast-enhanced CT scanning of the chest and abdomen is recommended in all patients with suspected lung cancer, regardless of chest x-ray scan findings (D) A tissue diagnosis should not be inferred from CT appearances alone (D) CT scanning should be performed before further diagnostic investigations, including bronchoscopy, and the results should be used to guide the investigation that is most likely to provide both a diagnosis and the stage the disease to the highest level (D) Supporting evidence: Review of 4 CT scan studies showing CT scans have good sensitivity (89%–100%) but low specificity (56%–63%) in differentiating malignant from benign solitary pulmonary nodules, which might be improved with serial scans
• ACCP (Kvale,¹⁵ 2006)	Summary of review: Patients with chest x-ray scan results negative for lung cancer might show positive results with bronchoscopy or CT imaging

Recommendations for further management of symptomatic patients or patients with abnormal results
• NICE,⁹ 2005	Recommendations: A patient who presents with symptoms suggestive of lung cancer should be referred to a team specializing in the management of lung cancer, depending on local arrangements (D) Immediate referral should be considered for signs of superior vena caval obstruction (swelling of the face or neck with fixed elevation of jugular venous pressure) or stridor (C) An urgent referral should be made for any of the following: persistent hemoptysis in smokers or former smokers aged 40 y and older (D); patients with chest x-ray scan findings suggestive of lung cancer (including pleural effusion and slowly resolving consolidation) (D); individuals with a history of asbestos exposure and a chest x-ray scan showing a pleural effusion, pleural mass, or any suspicious lung pathology (C)
• NZGG,¹⁰ 2009	Recommendations: Patients should be referred urgently to specialists if they have persistent hemoptysis and are smokers or former smokers aged 40 y or older or have chest x-ray scan findings suggestive of lung cancer (including pleural effusion or slowly resolving consolidation) (C) A person with risk factors for lung cancer who has consolidation on an initial chest x-ray scan should have a repeat chest x-ray scan within 6 wk to confirm resolution (√)
• Australian,¹⁷ 2004	Recommendation: All individuals with suspected lung cancer should be referred to a specialist with expertise in the management of lung disease for an opinion (IV)
• SIGN,¹⁸ 2005	Recommendations: Patients should be referred urgently to a chest physician for any of the following (D): persistent hemoptysis in smokers or former smokers older than 40 y of age; chest x-ray scan findings suggestive of or suspicious for lung cancer (including pleural effusion and slowly resolving or recurrent consolidation); signs of superior vena caval obstruction (swelling of the face and or neck with fixed elevation of jugular venous pressure); or stridor (emergency referral)
• ACCP (Gould et al,¹⁴ 2007)	Recommendation: In a patient with a single pulmonary nodule, the clinician should estimate the pretest probability of malignancy either qualitatively by using clinical judgment or quantitatively using a validated model (1C)

Recommendations for further management of ongoing suspicion of lung cancer despite normal initial investigation findings
• NICE,⁹ 2005	Recommendation: If chest x-ray scan findings are normal but there is a high suspicion of lung cancer, patients should be offered an urgent referral (D)
• NZGG,¹⁰ 2009	Recommendation: A person should be referred urgently to a specialist if they have normal chest x-ray scan findings but there is a high suspicion of lung cancer (C)
• NZGG,¹⁰ 2009	Supporting evidence: Based on a publication that found up to a quarter of lung cancer patients had negative chest x-ray scan results in primary care in the year before diagnosis in people with common symptoms of lung cancer, with the exception of hoarseness,³¹ suggesting not to over-rely on negative chest x-ray scan findings if there is a suspicion of lung cancer
• SIGN,¹⁸ 2005	Recommendation: Even with normal chest x-ray scan findings, patients who have experienced unexplained, nonspecific symptoms (eg, fatigue) potentially attributable to lung cancer, for more than 6 wk should be referred urgently to a respiratory physician (D)
• ACCP (Gould et al,¹⁴ 2007)	Recommendation: In a patient with a single pulmonary nodule that is stable on imaging tests for at least 2 y, no additional diagnostic evaluation should be performed, except for patients with pure ground-glass opacities on CT, for whom a longer duration of annual follow-up should be considered (2C)
• ACCP (Gould et al,¹⁴ 2007)	Supporting evidence: No evidence was found to suggest extending follow-up beyond 2 y that would detect more malignant nodules or improve patient outcomes

Recommendations for the use of sputum cytology in the investigation of suspected lung cancer
• NICE,⁹ 2005	Recommendation: Sputum cytology is not a discriminatory investigation in symptomatic patients (C)
• NZGG,¹⁰ 2009	Recommendation: Sputum cytology is not recommended for the investigation of lung cancer (√)
• Australian,¹⁷ 2004	Recommendation: Sputum cytology is recommended to help establish a positive diagnosis of lung cancer in individuals with a central pulmonary mass (III)
• Australian,¹⁷ 2004	Supporting evidence: Based on 5 studies. The sensitivity of sputum cytology increases with the number of specimens obtained—from about 50% with a single specimen up to almost 90% with 3 or more specimens. The use of induced ultrasonic nebulized sputum and optimal processing also increases the sensitivity of sputum cytology for the detection of lung cancer. Sensitivity is highest with centrally placed squamous cell carcinomas and lowest with both peripheral tumours and centrally placed small cell carcinomas. In an editorial,³² a specificity of 97.9% was reported
• SIGN,¹⁸ 2005	Recommendation: Sputum cytology should only be used in patients with large central lesions, for whom bronchoscopy or other diagnostic tests are deemed unsafe (D)
• SIGN,¹⁸ 2005	Supporting evidence: Based on 3 studies that showed a wide variation in sensitivity (10% to 97%) in diagnosis of lung cancer that was dependent upon the techniques of sample collection
• ACCP (Rivera and Mehta,¹⁶ 2007)	Recommendation: In a patient suspected of having lung cancer who presents with a central lesion with or without radiographic evidence of metastatic disease, in whom a semi-invasive procedure such as bronchoscopy or transthoracic needle aspiration might pose a higher risk, sputum cytology is recommended as an acceptable method of establishing the diagnosis. However, the sensitivity of sputum cytology varies by the location of the lung cancer. It is recommended that further testing be performed with a nondiagnostic sputum cytology test if the suspicion of lung cancer remains (1C)
• ACCP (Rivera and Mehta,¹⁶ 2007)	Supporting evidence: Based on 17 studies with a pooled sensitivity of 66% and pooled specificity of 99% for sputum cytology. Sensitivity was highly variable across studies with no explanation

Recommended wait timelines
• NICE,⁹ 2005	Recommendation: A report of chest x-ray scan findings should be made back to the referring primary health care professional within 5 d
• NZGG,¹⁰ 2009	Recommendation: After urgent referral for chest x-ray scan, the scan should be completed and reported within 1 wk (√)
• SIGN,¹⁸ 2005	Recommendations: Patients referred to a respiratory physician should be seen promptly, ideally within 2 wk (√) Pathways for patients with suspected or confirmed lung cancer should be reviewed by managed clinical networks with a view to implementing fast-track models for assessing these patients

ACCP—American College of Chest Physicians, COPD—chronic obstructive pulmonary disease, CT—computed tomography, NICE—National Institute for Health and Care Excellence, NZGG—New Zealand Guidelines Group, SIGN—Scottish Intercollegiate Guidelines Network.

For NICE, a rating of C means the recommendation is based directly on level III evidence or extrapolated from level I or level II evidence; a rating of D means the recommendation is based directly on level IV evidence or extrapolated from level I, level II, or level III evidence. Levels of evidence are defined by NICE as follows: Ia—systematic review or meta-analysis of randomized controlled trials; Ib—at least 1 randomized controlled trial; IIa—at least 1 well designed controlled study without randomization; IIb—at least 1 well designed quasi-experimental study, such as a cohort study; III—well designed non-experimental descriptive studies, case-control studies, and case series; IV—expert committee reports and opinions or clinical experience of respected authorities.

^†

For NZGG, a rating of C means the recommendation is supported by international expert opinion. In the NZGG guideline, where no evidence is available, best practice recommendations are made based on the experience of the Guideline Development Team or on feedback from consultation within New Zealand; these recommendations are identified by √. Levels of evidence for the Australian 2004 guideline are defined as follows: III-1—evidence obtained from well designed pseudo-randomized controlled trials (alternate allocation or some other method); III-2—evidence obtained from comparative studies with concurrent controls and allocation not randomized (cohort studies), case-control studies, or interrupted time series with a control group; III-3—evidence obtained from comparative studies with historical control, 2 or more single-arm studies, or interrupted time series without a parallel control group; IV—evidence obtained from case series, either posttest or pretest and posttest.

^‡

For SIGN, a rating of D means the recommendation is based on level 3 or 4 evidence or is extrapolated evidence from studies rated as 2+. Recommended best practice based on the clinical experience of the guideline development group is identified by √. Levels of evidence are defined by SIGN as follows: 2+ ratings are well conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal; 2- ratings are case-control or cohort studies with a high risk of confounding or bias and a substantial risk that the relationship is not causal; 3 ratings are nonanalytic studies (eg, case reports, case series); 4 ratings are expert opinion.

^§

For the ACCP guidelines, evidence graded as low to very low quality is based on observational studies or case series; 1C evidence is low to very low quality.