Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the full-text guideline document.
The grades of recommendations (A-D) and levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field.
Presentation and Referral
Symptoms and Signs
D - Patients should be referred urgently for a chest X-ray if they have experienced unexplained or persistent haemoptysis.
D - Patients should be referred for a chest X-ray if any of the following symptoms persist for more than three weeks without an obvious cause:
- Cough
- Chest/shoulder pain
- Dyspnoea
- Weight loss
- Chest signs
- Hoarseness
- Finger clubbing
- Features suggestive of metastases from lung cancer (e.g., brain, bone, liver or skin)
- Persistent cervical/supraclavicular lymphadenopathy
Referral to a Respiratory Physician
D - Patients should be referred urgently to a chest physician if they have any of the following:
- Persistent haemoptysis in smokers or ex-smokers over 40 years of age
- A chest x-ray suggestive or suspicious of 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)
- Stridor (emergency referral).
D - Even with a normal chestxX-ray, patients who have experienced unexplained, nonspecific symptoms (e.g., fatigue potentially attributable to lung cancer) for more than six weeks should be referred urgently to a respiratory physician.
Fast Track Systems
D - 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.
Diagnostic Investigations
Imaging
D - A chest x-ray should be performed on all patients being investigated for the possibility of lung cancer.
D - Contrast enhanced computed tomography (CT) scanning of the chest and abdomen is recommended in all patients with suspected lung cancer, regardless of chest x-ray results.
D - A tissue diagnosis should not be inferred from CT appearances alone.
D - CT scanning should be performed prior to further diagnostic investigations, including bronchoscopy, and the results used to guide the investigation that is most likely to provide both a diagnosis and stage the disease to the highest level.
D - NeoSPECT (Tc-99m depreotide, an imaging agent which binds to somatostatin receptors on malignant tumours) scanning should be considered as an investigation in patients presenting with solitary pulmonary nodules but histological confirmation will usually be required.
C - Positron emission tomography (PET) scanning may be used to investigate patients presenting with solitary lung lesions but histological/cytological confirmation of results will still be required.
Bronchoscopy
B - Patients with central lesions who are otherwise fit should undergo flexible bronchoscopy in order to establish a histological or cytological diagnosis.
B - Visible tumours should be sampled using more than one technique to optimize sensitivity.
B - Bronchoscopy may provide a diagnosis for peripheral lesions, although percutaneous fine needle aspiration (FNA)/biopsy is the preferred approach.
Percutaneous FNA/Biopsy
B - Percutaneous FNA/biopsy should be considered as the preferred diagnostic technique in patients with peripheral lesions.
Sputum Cytology
D - Sputum cytology should only be used in patients with large central lesions, where bronchoscopy or other diagnostic tests are deemed unsafe.
Video-Assisted Thoracoscopy
D - Thoracoscopy should be considered for patients with suspected lung cancer where less invasive means have not achieved histological and cytological confirmation of diagnosis.
Staging
T Stage in Non-Small Cell Lung Cancer (NSCLC)
B - Patients with suspected T3 or T4 disease who are otherwise fit for surgery should not be denied surgical exploration on the basis of a CT alone.
B - Magnetic resonance imaging (MRI) is not recommended in the routine assessment of the T stage except in patients with superior sulcus tumours. It may be of value in selected patients with suspected mediastinal invasion.
C - Thoracoscopy may be considered for more accurate determination of the T stage in patients with suspected mediastinal or chest wall invasion when less invasive techniques have been inconclusive.
D - In patients being considered for curative therapy, pleural effusion should be investigated with pleural aspiration and/or pleural biopsy.
D- The presence of malignant cells is required to categorise the lesion as T4.
N Stage in NSCLC
B - A positive CT scan result for mediastinal lymphadenopathy indicates the need for surgical biopsy of the enlarged nodes, regardless of size or site (with the exception of extensive infiltrating disease).
B - Patients with small peripheral tumours and a negative CT scan of the mediastinum require no further investigation. Otherwise it is reasonable to further investigate the mediastinum with mediastinoscopy or PET prior to performing a thoracotomy.
B - MRI has no role in the routine staging of mediastinal lymphadenopathy.
C - Mediastinoscopy should be used to stage the mediastinum where possible.
C - Inaccessible nodal stations can be staged using thoracoscopy, endoscopic ultrasound (EUS) FNA, endobronchial ultrasound (EBUS) FNA, percutaneous CT guided biopsy, extended cervical mediastinoscopy or parasternal mediastinotomy, as appropriate to the patient's circumstances.
C - Patients with a negative CT scan result for mediastinal adenopathy should proceed to PET, except for those with small peripheral tumours.
C - Patients with a negative PET scan result for mediastinal adenopathy should proceed to thoracotomy.
C - Patients with a positive PET scan result for mediastinal adenopathy require histological confirmation.
M Stage in NSCLC
C - Patients staged as cI-II on the basis of a chest CT and a negative clinical evaluation do not require further investigation to look for extrathoracic metastases.
C - Patients staged as cIII following clinical evaluation may require further investigation for distant metastases.
C - Contrast enhanced head CT or MRI in patients with cI-II disease is not recommended.
B - A positive bone scan in patients with otherwise potentially curable disease must be confirmed by other studies (e.g., plain X-rays, MRI or biopsy).
C - Ultrasound (US), CT or MRI can be used to characterise most benign focal hepatic abnormalities >1cm.
C - A definitive confirmation of a liver metastasis can only be made by needle biopsy.
C - The management of patients with lesions too small to characterise by imaging and not amenable to biopsy is best guided by an estimation of the chance of metastatic disease given the clinical stage and symptoms.
B - It may be reasonable to forego further investigation of adrenal glands <2 cm, in patients who are stage cI-II and who have a negative clinical evaluation
B - Patients having adrenal gland nodules >2 cm, should proceed to further imaging studies and biopsy as necessary.
C - Patients with small pulmonary nodules should not be denied a curative approach without a definitive diagnosis (by biopsy, FNA or wedge resection).
Staging Small Cell Lung Cancer (SCLC)
B - Investigation for distant metastases is recommended when intensive treatment is being considered for patients with SCLC who are considered to be at high risk of having distant metastases.
Surgery
NSCLC
D - Patients with stage I and II lung cancer should be considered for curative surgery whenever possible.
D - Lung resection should be as limited as possible without compromising cancer clearance. Lobectomy remains the procedure of choice for fit patients.
D - Every effort should be made to avoid a futile thoracotomy.
D - Video-assisted thorascopic surgery (VATS) resection, undertaken by an appropriately skilled surgeon, may be offered to selected patients with clinical stage I lung cancer.
B - Systematic mediastinal lymph node dissection is recommended as offering the best compromise between accuracy of staging and containment of morbidity.
D - Patients with superior sulcus tumours not involving the brachial plexus and with negative mediastinoscopy may be considered for resection.
B - Patients with a solitary synchronous or metachronous brain metastasis and otherwise potentially curative lung cancer:
- May be considered for resection of the metastasis
- Should be given adjuvant brain radiotherapy to reduce the risk of local recurrences
SCLC
A - Routine surgery for limited disease SCLC is not recommended.
D - Patients with early stage SCLC may be considered for resection following extensive staging investigation.
Management of Malignant Pleural Effusion
A - Talc is the optimal sclerosant for thoracoscopic pleurodesis in patients with a malignant pleural effusion who are fit enough to undergo sedation or general anaesthesia.
A - In patients who are unfit for a thoracoscopic procedure, tube thoracostomy pleurodesis using talc slurry should be performed.
Radiotherapy
NSCLC
B - Patients with NSCLC stage I and II who are medically inoperable or who do not consent to surgery should be offered radical radiotherapy.
B - Patients meeting the following criteria should be offered radical radiotherapy:
- IIIA or IIIB disease, as long as the tumour can be safely encompassed within a radical radiotherapy volume
- World Health Organization (WHO) performance status (PS) 0 or 1
- Less than 10% weight loss
A - Patients having radical radiotherapy should be given Continuous Hyperfractionated Accelerated Radiation Therapy (CHART) (54Gy/36F/12 days) in preference to 60Gy/30F/6W.
Small Cell and NSCLC
A - Patients with thoracic symptoms and good performance status not suitable for radical radiotherapy should be considered for more fractionated, higher dose regimens of palliative radiotherapy, such as 39Gy/13F.
A - Patients with thoracic symptoms and poor performance status not suitable for radical radiotherapy should receive palliative radiotherapy with regimens of 10Gy/1F or 16Gy/2F.
B - Patients with single brain metastases should be offered resection followed by whole brain radiotherapy.
A - Patients with lung cancer and symptomatic bone metastases should be treated with a single 8Gy fraction of palliative radiotherapy.
A - Selected patients with unresectable and/or multiple brain metastases and good performance status should be considered for fractionated palliative radiotherapy (e.g., 20Gy/5F).
Chemotherapy
Chemotherapy for Patients with Stage IIIB and IV NSCLC
A - Chemotherapy with a platinum-based combination doublet regimen should be considered in all patients who are not suitable for curative resection or radical radiotherapy and are fit enough to receive it.
A - Selected older patients with stage III/IV NSCLC should be offered chemotherapy.
A - For patients with advanced NSCLC the number of chemotherapy cycles should not exceed four.
A - Second line chemotherapy with docetaxel 75 mg/m2 (three weekly) should be considered for stage IIIB/IV NSCLC patients with good performance status.
Chemotherapy for Patients with SCLC
A - Combination intravenous chemotherapy should be considered for SCLC patients over 70 years of age with performance status 0-2.
A - A regimen containing a platinum agent and etoposide is recommended for first line treatment of patients with SCLC.
A - In patients with SCLC the recommended number of chemotherapy cycles is three to six.
B - Second line chemotherapy in patients with SCLC should be considered depending on the duration of response to first line chemotherapy and on patients' performance status and wishes.
B - Maintenance chemotherapy following first line treatment is not recommended.
Reducing Toxicity in NSCLC and SCLC
A - The routine use of growth factors in supporting patients during chemotherapy is not recommended.
A - Amifostine should not be used with cisplatin (<80 mg/m2) outwith clinical trials.
Administration of Chemotherapy
D - Staff should be experienced and trained in safe prescribing, preparation and administration of chemotherapy and be involved in ongoing continuous professional development and reappraisal.
D - Hospital based administration of chemotherapy should take place during the working day in designated areas equipped to deal with any medical emergencies.
Combined Modalities
Preoperative (Neoadjuvant) Chemotherapy in NSCLC Patients Undergoing Curative Surgery Plus Radiotherapy
D - There is no role for preoperative chemoradiation outside clinical trials.
Postoperative (Adjuvant) Chemotherapy in NSCLC Patients Undergoing Curative Surgery
A - Adjuvant chemotherapy should be considered for resected NSCLC, but discussed fully given the small margin of benefit, risk of toxicity and uncertainty as to which group of patients is most likely to benefit.
Postoperative (Adjuvant) Radiotherapy in NSCLC Patients Undergoing Curative Surgery
A - Patients with NSCLC who have had complete tumour resection should not receive postoperative radiotherapy, except as part of a randomised trial.
Neoadjuvant and Adjuvant Chemotherapy in NSCLC Patients Undergoing Radical Radiotherapy
A - Platinum-based combination chemotherapy should be considered for good performance status patients with locally advanced disease who are to be treated with radical radiotherapy at standard fractionation (e.g., 60Gy/30F/6W).
Consolidation Thoracic Radiotherapy in Patients with Limited SCLC Disease
A - Consolidation thoracic radiotherapy should be considered for patients with limited disease SCLC who have achieved complete response or partial response following chemotherapy.
Prophylactic Cranial Radiotherapy in SCLC Patients with Limited Disease
A - Prophylactic cranial radiotherapy should be offered to patients with limited disease SCLC achieving remission after chemotherapy.
Endobronchial and Vascular Therapies
Endobronchial Treatments
D - Photodynamic therapy (PDT) may be useful as a treatment option for early stage lung cancer in patients who are inoperable for medical reasons.
D - Photodynamic therapy may contribute to the control of pulmonary symptoms in patients with locally advanced disease.
D - Endobronchial treatments such as brachytherapy, electrocautery, cryosurgery, Nd-YAG laser therapy and stents, may be useful in relieving malignant airway obstruction where standard treatments (e.g., external beam radiotherapy) have failed.
Management of Superior Vena Cava Obstruction (SVCO)
B - In patients with SVCO due to SCLC, chemotherapy/radiotherapy is recommended as initial treatment, but stenting may be considered for relapse or persistent SVCO.
Multidisciplinary Teams, Follow Up and Communication
Role of the Multidisciplinary Team
D - All patients with a diagnosis of lung cancer should have their treatment and management planned and directed by a multidisciplinary team.
D - Allied health professional services should be offered to all patients with lung cancer.
Follow Up
B - Follow up by clinical nurse specialists should complement conventional arrangements.
D - Hospital follow up should be continued where hospital treatment or specialist advice is still required, or whilst clinical trials are ongoing.
D - After surgery, the surgeon should follow up all patients initially: later follow up should be according to local policy.
D - After palliative therapy is completed, follow up should be agreed between the oncologist, respiratory physician, general practitioner (GP) and palliative care team.
Communication
A - Communication skills training should be provided across the Multidisciplinary Team (MDT).
Supportive and Palliative Care
Specialist Palliative Care Services
B - All patients with lung cancer should have access to a specialist palliative care team.
Symptom Management
D - Symptoms should be assessed regularly and appropriate interventions initiated by the full multidisciplinary team.
Definitions:
Levels of Evidence
1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias
1+: Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1 -: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2++: High quality systematic reviews of case control or cohort studies; high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+: 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-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3: Non-analytic studies (e.g., case reports, case series)
4: Expert opinion
Grades of Recommendation
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.
A: At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D: Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group
