The strength of recommendation grading (A-D (GPP)) and level of evidence (1++-4) for interventional studies and strength of recommendation grading A (DS) - D (DS) and level of evidence (Ia - IV) for diagnostic studies are defined at the end of the "Major Recommendations" field.
Access to Services
D (GPP) - All patients diagnosed with lung cancer should be offered information, both verbal and written, on all aspects of their diagnosis, treatment and care. This information should be tailored to the individual requirements of the patient, and audio and videotaped formats should also be considered.
D (GPP) - Treatment options and plans should be discussed with the patient and decisions on treatment and care should be made jointly with the patient. Treatment plans must be tailored around the patient's needs and wishes to be involved, and his or her capacity to make decisions.
D (GPP) - The public needs to be better informed of the symptoms and signs that are characteristic of lung cancer, through co-ordinated campaigning to raise awareness.
D - Urgent referral for a chest X-ray should be offered when a patient presents with:
- haemoptysis, or
- any of the following unexplained or persistent (that is, lasting more than 3 weeks) symptoms or signs:
- cough
- chest/shoulder pain
- dyspnoea
- weight loss
- chest signs
- hoarseness
- finger clubbing
- features suggestive of metastasis from a lung cancer (for example in brain, bone, liver or skin)
- cervical/supraclavicular lymphadenopathy
D - If a chest X-ray or chest computerised tomography (CT) scan suggests lung cancer (including pleural effusion and slowly resolving consolidation), patients should be offered an urgent referral to a member of the lung cancer multidisciplinary team (MDT), usually a chest physician.
D - If the chest X-ray is normal but there is a high suspicion of lung cancer, patients should be offered urgent referral to a member of the lung cancer MDT, usually the chest physician.
D - Patients should be offered an urgent referral to a member of the lung cancer MDT, usually the chest physician, while awaiting the result of a chest X-ray, if any of the following are present:
- persistent haemoptysis in smokers/ex-smokers over 40 years of age
- signs of superior vena caval obstruction (swelling of the face/neck with fixed elevation of jugular venous pressure)
- stridor
Emergency referral should be considered for patients with superior vena cava obstruction or stridor.
Diagnosis
D (GPP) - Where a chest X-ray has been requested in primary or secondary care and is incidentally suggestive of lung cancer, a second copy of the radiologist's report should be sent to a designated member of the lung cancer MDT, usually the chest physician. The MDT should have a mechanism in place to follow up these reports to enable the patient's General Practitioner (GP) to have a management plan in place.
D (GPP) - Patients with known or suspected lung cancer should be offered a contrast-enhanced chest CT scan to further the diagnosis and stage the disease. The scan should also include the liver and adrenals.
Chest CT should be performed before:
- A; C(DS) - an intended fibreoptic bronchoscopy
- D (GPP) - any other biopsy procedure
B (DS) - Bronchoscopy should be performed on patients with central lesions who are able and willing to undergo the procedure.
B (DS) - Sputum cytology is rarely indicated and should be reserved for the investigation of patients who have centrally placed nodules or masses and are unable to tolerate, or unwilling to undergo, bronchoscopy or other invasive tests.
B (DS) - Percutaneous transthoracic needle biopsy is recommended for diagnosis of lung cancer in patients with peripheral lesions.
B (DS) - Surgical biopsy should be performed for diagnosis where other less invasive methods of biopsy have not been successful or are not possible.
D (GPP) - Where there is evidence of distant metastases, biopsies should be taken from the metastatic site if this can be achieved more easily than from the primary site.
C; B (DS) - An 18F-deoxyglucose positron emission tomography (FDG-PET) scan should be performed to investigate solitary pulmonary nodules in cases where a biopsy is not possible or has failed, depending on nodule size, position and CT characterisation.
Staging
Non-Small Cell Lung Cancer (NSCLC)
In the assessment of mediastinal and chest wall invasion:
- B (DS) - CT alone may not be reliable
- D (GPP) - other techniques such as ultrasound should be considered where there is doubt
- D (GPP) - surgical assessment may be necessary if there are no contraindications to resection.
C (DS) - Magnetic resonance imaging (MRI) should not routinely be performed to assess the stage of the primary tumour (T-stage) in NSCLC.
B (DS) - MRI should be performed, where necessary to assess the extent of disease, for patients with superior sulcus tumours.
D (GPP) - Every cancer network should have a system of rapid access to FDG-PET scanning for eligible patients.
A (DS) - Patients who are staged as candidates for surgery on CT should have an FDG-PET scan to look for involved intrathoracic lymph nodes and distant metastases.
D (GPP)- Patients who are otherwise surgical candidates and have, on CT, limited (1-2 stations) N2/3 disease of uncertain pathological significance should have an FDG-PET scan.
B (DS) - Patients who are candidates for radical radiotherapy on CT should have an FDG-PET scan.
A - Patients who are staged as N0 or N1 and M0 (stages I and II) by CT and FDG-PET and are suitable for surgery should not have cytological/histological confirmation of lymph nodes before surgical resection.
B (DS) - Histological/cytological investigation should be performed to confirm N2/3 disease where FDG-PET is positive. This should be achieved by the most appropriate method. Histological/cytological confirmation is not required:
- where there is definite distant metastatic disease
- where there is a high probability that the N2/N3 disease is metastatic (for example, if there is a chain of high FDG uptake in lymph nodes).
B (DS) - When an FDG-PET scan for N2/N3 disease is negative, biopsy is not required even if the patient's nodes are enlarged on CT.
D (GPP) - If FDG-PET is not available, suspected N2/3 disease, as shown by CT scan (nodes with a short axis > 1cm), should be histologically sampled in patients being considered for surgery or radical radiotherapy.
D (GPP) - An MRI or CT scan should be performed for patients with clinical signs or symptoms of brain metastasis.
D (GPP) - An X-ray should be performed in the first instance for patients with localised signs or symptoms of bone metastasis. If the results are negative or inconclusive, either a bone scan or an MRI scan should be considered.
Small Cell Lung Cancer
D (GPP) - SCLC should be staged by a contrast-enhanced CT scan of the patient's chest, liver and adrenals and by selected imaging of any symptomatic area.
Surgery with Curative Intent for Patients with NSCLC
D - Surgical resection is recommended for patients with stage I or II NSCLC who have no medical contraindications and adequate lung function.
C - For patients with stage I or II NSCLC who can tolerate lobar resection, lobectomy is the procedure of choice.
D - Pending further research, patients with stage I or II NSCLC who would not tolerate lobectomy because of comorbid disease or pulmonary compromise should be considered for limited resection or radical radiotherapy.
D (GPP) - For all patients with stage I or II NSCLC undergoing surgical resection -- usually a lobectomy or a pneumonectomy -- clear surgical margins should be the aim.
C - Sleeve lobectomy offers an acceptable alternative to pneumonectomy for patients with stage I or II NSCLC who have an anatomically appropriate (central) tumour. This has the advantage of conserving functioning lung.
C - For patients with T3 NSCLC with chest wall involvement who are undergoing surgery, complete resection of the tumour should be the aim by either extrapleural or en bloc chest wall resection.
D (GPP) - All patients undergoing surgical resection for lung cancer should have systematic lymph node sampling to provide accurate pathological staging.
D (GPP) - In patients with stage IIIA (N2) NSCLC detected through preoperative staging, surgery alone is associated with a relatively poor prognosis. Therefore, these patients should be evaluated by the lung cancer MDT.
Radical Radiotherapy Alone for Treatment of NSCLC
D (GPP) - Radical radiotherapy is indicated for patients with stage I, II or III NSCLC who have good performance status (WHO 0, 1) and whose disease can be encompassed in a radiotherapy treatment volume without undue risk of normal tissue damage.
D (GPP) - All patients should undergo pulmonary function tests (including lung volumes and transfer factor) before having radical radiotherapy for NSCLC.
D (GPP) - Patients who have poor lung function but are otherwise suitable for radical radiotherapy should still be offered radiotherapy, provided the volume of irradiated lung is small.
A - Patients with stage I or II NSCLC who are medically inoperable but suitable for radical radiotherapy should be offered the CHART regimen.
A - Patients with stages IIIA or IIIB NSCLC who are eligible for radical radiotherapy and who cannot tolerate or do not wish to have chemoradiotherapy should be offered the CHART regimen.
D (GPP) - If CHART is not available, conventionally fractionated radiotherapy to a dose of 64 to 66 Gy in 32 to 33 fractions over 6 1/2 weeks or 55 Gy in 20 fractions over 4 weeks should be offered.
Chemotherapy for NSCLC
A - Chemotherapy should be offered to patients with stage III or IV NSCLC and good performance status (WHO 0, 1 or a Karnofsky score of 80-100), to improve survival, disease control and quality of life.
D (GPP) - Chemotherapy for advanced NSCLC should be a combination of a single third-generation drug (docetaxel, gemcitabine, paclitaxel or vinorelbine) plus a platinum drug. Either carboplatin or cisplatin may be administered, taking account of their toxicities, efficacy and convenience.
A - Patients who are unable to tolerate a platinum combination may be offered single-agent chemotherapy with a third-generation drug.
A - Docetaxel monotherapy should be considered if second-line treatment is appropriate for patients with locally advanced or metastatic NSCLC in whom relapse has occurred after previous chemotherapy.
The development of this section included a review of the following technology appraisal. "Docetaxel, paclitaxel, gemcitabine and vinorelbine for non-small cell lung cancer. NICE Technology Appraisal No. 26 (2001)". The appraisal is therefore now obsolete and has been replaced by the guideline.
Combination Treatment for NSCLC
B - Patients with stage I, II or IIIA NSCLC who are suitable for resection should not be offered preoperative chemotherapy unless it is part of a clinical trial.
A - Preoperative radiotherapy is not recommended for patients with NSCLC who are able to have surgery.
A - Postoperative radiotherapy is not recommended for patients with NSCLC after complete resection.
D - Postoperative radiotherapy should be considered after incomplete resection of the primary tumour for patients with NSCLC, with the aim of improving local control.
A - Adjuvant chemotherapy should be offered to NSCLC patients who have had a complete resection, with discussion of the risks and benefits.
B - Patients who are pathologically staged as II and III NSCLC following resection should not receive postoperative chemoradiotherapy unless it is within a clinical trial.
A - Patients with stage III NSCLC who are not suitable for surgery but are eligible for radical radiotherapy should be offered sequential chemoradiotherapy.
Treatment of Small Cell Lung Cancer (SCLC)
D - Patients with SCLC should be offered an assessment that includes evaluation of the major prognostic factors: performance status, serum lactate dehydrogenase, liver function tests, serum sodium, and stage.
All patients with SCLC should be offered:
- A - platinum-based chemotherapy
- A - multidrug regimens, because they are more effective and have a lower toxicity than single-agent regimens.
A - Four to six cycles of chemotherapy should be offered to patients whose disease responds. Maintenance treatment is not recommended.
A - Patients with limited-stage SCLC should be offered thoracic irradiation concurrently with the first or second cycle of chemotherapy or following completion of chemotherapy if there has been at least a good partial response within the thorax. For patients with extensive disease, thoracic irradiation should be considered following chemotherapy if there has been a complete response at distant sites and at least a good partial response within the thorax.
D (GPP) - Patients undergoing consolidation thoracic irradiation should receive a dose in the range of 40 Gy in 15 fractions over 3 weeks to 50 Gy in 25 fractions over 5 weeks.
A - Patients with limited disease and complete or good partial response after primary treatment should be offered prophylactic cranial irradiation.
D (GPP) - Second-line chemotherapy should be offered to patients at relapse only if their disease responded to first-line chemotherapy. The benefits are less than those of first-line chemotherapy.
Palliative Interventions and Supportive and Palliative Care
This section focuses on palliative interventions and supportive and palliative care for patients with lung cancer and therefore only evidence specific to lung cancer was reviewed. An absence of evidence does not imply that nothing can be done to help, and supportive and palliative care multidisciplinary teams - in particular specialist palliative care teams - have an important role in symptom control.
D (GPP) - Supportive and palliative care of the patient should be provided by general and specialist palliative care providers in accordance with the NICE guidance "Improving supportive and palliative care for adults with cancer."
D (GPP) - Patients who may benefit from specialist palliative care services should be identified and referred without delay.
A - External beam radiotherapy should be considered for the relief of breathlessness, cough, haemoptysis or chest pain.
A - Opioids, such as codeine or morphine, should be considered to reduce cough.
D - Debulking bronchoscopic procedures should be considered for the relief of distressing large-airway obstruction or bleeding due to an endobronchial tumour within a large airway.
D - Patients with endobronchial symptoms that are not palliated by other means may be considered for endobronchial therapy.
D - Patients with extrinsic compression may be considered for treatment with stents.
A - Non-drug interventions based on psychosocial support, breathing control and coping strategies should be considered for patients with breathlessness.
D (GPP) - Non-drug interventions for breathlessness should be delivered by a multidisciplinary group, co-ordinated by a professional with an interest in breathlessness and expertise in the techniques (for example, a nurse, physiotherapist or occupational therapist). Although this support may be provided in a breathlessness clinic, patients should have access to it in all care settings.
D (GPP) - Patients with troublesome hoarseness due to recurrent laryngeal nerve palsy should be referred to an ear, nose and throat specialist for advice.
A - Patients who present with superior vena cava obstruction should be offered chemotherapy and radiotherapy according to the stage of disease and performance status.
B - Stent insertion should be considered for the immediate relief of severe symptoms of superior vena caval obstruction or following failure of earlier treatment.
D - Corticosteroids and radiotherapy should be considered for symptomatic treatment of cerebral metastases in lung cancer.
D (GPP) - Other symptoms, including weight loss, loss of appetite, depression and difficulty swallowing, should be managed by multidisciplinary groups that include supportive and palliative care professionals.
B - Pleural aspiration or drainage should be performed in an attempt to relieve the symptoms of a pleural effusion.
B - Patients who benefit symptomatically from aspiration or drainage of fluid should be offered talc pleurodesis for longer-term benefit.
B - For patients with bone metastasis requiring palliation and for whom standard analgesic treatments are inadequate, single-fraction radiotherapy should be administered.
D - Spinal cord compression is a medical emergency and immediate treatment (within 24 hours), with corticosteroids, radiotherapy and surgery where appropriate, is recommended.
D (GPP) - Patients with spinal cord compression should have an early referral to an oncology physiotherapist and an occupational therapist for assessment, treatment and rehabilitation.
Service Organization
D - All patients with a likely diagnosis of lung cancer should be referred to a member of a lung cancer MDT (usually a chest physician).
D - The care of all patients with a working diagnosis of lung cancer should be discussed at a lung cancer MDT meeting.
A- Early diagnosis clinics should be provided where possible for the investigation of patients with suspected lung cancer, because they are associated with faster diagnosis and less patient anxiety.
D - All cancer units/centres should have one or more trained lung cancer nurse specialists to see patients before and after diagnosis, to provide continuing support, and to facilitate communication between the secondary care team (including the MDT), the patient's GP, the community team and the patient. Their role includes helping patients to access advice and support whenever they need it.
D - Patients who have lung cancer suitable for radical treatment or chemotherapy, or need radiotherapy or ablative treatment for relief of symptoms, should be treated without undue delay, according to the Welsh Assembly Government and Department of Health recommendations (within 31 days of the decision to treat and within 62 days of their urgent referral).
A - Patients who cannot be offered curative treatment, and are candidates for palliative radiotherapy, may either be observed until symptoms arise and then treated, or be treated with palliative radiotherapy immediately.
D (GPP) - When patients finish their treatment a personal follow-up plan should be discussed and agreed with them after discussion with the professionals involved in the patient's care. GPs should be informed of the plan.
A - After completion of their treatment, patients with an expectation of life of more than 3 months should have access to protocol-controlled, nurse-led follow-up.
D - Patients who have had attempted curative surgery for NSCLC or radical radiotherapy should be followed up routinely by a member of the MDT for up to 9 months to check for post-treatment complications. Thoracic imaging should be part of the review.
D - For patients who have had attempted curative surgery for NSCLC, any routine follow-up should not extend beyond 5 years.
D - Patients who have had palliative radiotherapy or chemotherapy should be followed up routinely at 1 month after completion of treatment. A chest X-ray should be part of the review if clinically indicated.
D - Patients with lung cancer -- in particular those with a better prognosis -- should be encouraged to stop smoking.
D (GPP) - The opinions and experiences of lung cancer patients and carers should be collected and used to improve the delivery of lung cancer services. Patients should receive feedback on any action taken as a result of such surveys.
Definitions:
Levels of Evidence for Intervention Studies
1++: High quality meta-analyses, systematic reviews of randomized 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, bias, or chance and a high probability that the relationship is causal
2+: Well-conducted case control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal
2-: Case-control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3: Non-analytic studies (for example, case reports, case series)
4: Expert opinion
Levels of Evidence for Studies of the Accuracy of Diagnostic Tests
Ia: Systematic review (with homogeneity)* of level-1 studies**
Ib: Level-1 studies**
II: Level-2 studies*** Systematic reviews of level-2 studies
III: Level-3 studies**** Systematic reviews of level-3 studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience without explicit critical experience, based on physiology, bench research, or first principles.
*Homogeneity means there are no or minor variations in the directions and degrees of results between individual studies that are included in the systematic review.
**Level-1 studies are studies:
- That use a blind comparison of the test with a validated reference standard (gold standard)
- In a sample of patients that reflects the population to whom the test would apply.
***Level-2 studies are studies that have only one of the following:
- Narrow population (the sample does not reflect the population to whom the test would apply)
- Use a poor reference standard (defined as that where the 'test' is included in the 'reference', or where the 'testing' affects the 'reference')
- The comparison between the test and reference is not blind
- Case-control studies
****Level-3 studies are studies that have at least two or three of the features listed above.
Grading of Recommendations on Interventions
Grade A:
- At least one meta-analysis, systematic review, or randomized control trial (RCT) rated as 1++, and directly applicable to the target population, or
- A systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
- Evidence drawn from a National Institute for Health and Clinical Excellence (NICE) technology appraisal
Grade 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+
Grade 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++
Grade D:
- Evidence level 3 or 4, or
- Extrapolated evidence from studies rated as 2+, or
- Formal consensus
D (GPP):
A good practice point (GPP) is a recommendation for best practice based on the experience of the Guideline Development Group
Grading of Recommendations on Diagnostic Tests
Grade A (DS): Studies with level of evidence Ia or Ib
Grade B (DS): Studies with level of evidence II
Grade C (DS): Studies with level of evidence III
Grade D (DS): Studies with level of evidence IV
(DS = diagnostic studies)
