Dr David Baldwin explains how recent developments in the diagnostic, assessment, and treatment pathways are reflected in the updated NICE guideline on lung cancer


Lung cancer is a leading cause of cancer death: each year over 33,500 people die from this disease,1,2 which causes 4000 more deaths than breast and bowel cancer combined.3 Reducing mortality from lung cancer is therefore important if we are to achieve one of the aims of the Cancer Reform Strategy—to save 5000 lives by 2014/15.4 The median survival time for lung cancer in the UK is 202 days, and only 32% of patients survive for 1 year5

The NICE guideline on the management of lung cancer has been updated to reflect the modern approach to selecting the most effective treatment for patients.1,2 This article explains:

  • the importance of the GP’s role in ensuring a positive approach to early diagnosis and supportive management of lung cancer
  • how the update should enable GPs to offer better treatment to more patients.

Why update this guideline?

A significant amount of progress has been made since publication of the 2005 NICE guideline on lung cancer, in particular, the provision of new services such as positron emission tomography (PET) scanning and better access to existing diagnostic techniques. However, although improvements in 5-year survival and surgical resection rates are now being observed, they are modest and we know that there is marked variation in the delivery of active and curative treatments, within the UK.5,6 Increasing resection and treatment rates would allow scope for marked improvement in outcomes, possibly to levels observed in other countries.7 Thus, there is a need to encourage lung cancer teams to select patients correctly so that the most effective treatment can be offered. One of the key short-term surrogate measures for improvement in mortality is 1-year survival and this will be used to look for early signs of progress.4 Achievement of this outcome requires an effective integrated healthcare service that, at first sight, may seem dominated by secondary care, but in reality is critically dependent on primary care, where issues may be more difficult to tackle.

The key role of the GP

Early diagnosis, awareness, and referral
In the UK, almost three-quarters of patients with lung cancer present with advanced disease that is not amenable to curative treatment and 38% of them are first diagnosed following an emergency admission.4 Therefore, one of the key issues faced is how to ensure that patients recognise and report their symptoms early and are referred promptly. Recently, the National Awareness and Early Diagnosis Initiative (NAEDI) was launched to increase awareness of lung cancer symptoms8—GP referral of patients when they present with warning symptoms is key to successful implementation (see Box 1, below).

Communication
Effective integrated care should involve good communication between healthcare professionals and with patients to support them during difficult decision-making. The evidence for effective communication was reviewed and the following recommendations were made:1,2

  • Healthcare professionals should find out what the patient knows, provide accurate and easy-to-understand verbal and written information at appropriate times in the pathway, and support patients and carers as they receive information. The use of purpose-designed decision aids should be considered. There should be clear documentation and patients should be offered a copy. Information should be shared between healthcare professionals, including any advanced decisions (e.g. if the patient does not wish to undergo chemotherapy or invasive procedures). If the patient does not wish to confront issues, this should be respected
  • A lung cancer clinical nurse specialist should be available at all stages of care to support patients and carers.

Smoking cessation
Smoking cessation may seem futile or even cruel when patients have developed lung cancer, but we know that they can improve their survival if they quit smoking.9 Moreover, smoking cessation in the context of surgery reduces postoperative complications, such as with pulmonary rehabilitation. Patients should be advised of these benefits and supported if they wish to quit (e.g. by provision of smoking cessation aids). Surgery should not be postponed to allow patients to stop smoking.1,2

Follow up
A key new recommendation on patient follow up is that individuals are given regular rather than symptom-driven appointments. This is to avoid emergency readmission to hospital, which is often distressing, and to aid early identification and treatment of symptoms. All patients should be offered an initial specialist follow-up appointment to discuss ongoing care within 6 weeks of completing treatment. Thereafter, regular appointments should be provided, rather than relying on patients requesting appointments when they experience symptoms. A lung cancer clinical nurse specialist should offer protocol-driven follow up and it is important to ensure that patients know how to contact him/her.

Box 1: Early diagnosis, awareness, and referral1,2

The public needs to be better informed of the symptoms and signs that are characteristic of lung cancer; coordinated campaigning to raise awareness can help achieve this objective. Prompt attention to warning symptoms and promotion of public awareness of these signs will help to ensure that patients have the best chance of early diagnosis.

Referral
Offer urgent referral for a chest X-ray 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
    • hoarseness
    • weight loss
    • chest signs
    • finger clubbing
    • features suggestive of metastasis from a lung cancer (e.g. in brain, bone, liver, or skin)
    • cervical/supraclavicular lymphadenopathy
  • Offer urgent referral to a member of the lung cancer multidisciplinary team, usually a chest physician:
    • if lung cancer is indicated by an X-ray or computed tomography scan of the chest (including pleural effusion and slowly resolving consolidation)
    • if the chest X-ray is normal, but there is a high suspicion of lung cancer
    • while awaiting the result of a chest X-ray, if any of the following are present:
      • persistent haemoptysis in smokers/ex-smokers aged >40 years
      • signs of superior vena caval obstruction (swelling of the face/neck with fixed elevation of jugular venous pressure)
      • stridor.

Modernising diagnosis and treatment

Much of the updated NICE guideline is focused on modernising the diagnostic and staging approach, assessing fitness in detail, and encouraging the application of active treatments with the overall aim of reducing variation in standards of care and increasing active treatment rates. It is important that the GP has a feel for the often complex issues that the patient and healthcare professionals have to face. This understanding will help GPs to supply this modern approach to staging and diagnosis when patients come to them with difficult decisions that need to be made.

Selection of patients with lung cancer for intervention is often complex because of the need to be familiar with the diagnosis, stage, and the patient’s fitness for potential treatment. Fitness may influence the extent to which diagnosis and stage is pursued, and at all times the patient’s informed preferences must be respected. The new evidence-based diagnostic and staging algorithm for lung cancer is shown in Figure 1 (see below). It is of note that this pathway starts with a combined clinical and computed tomography (CT) assessment. The latter greatly increases the accuracy of the clinical assessment, providing essential diagnostic and staging information. On the basis of this information, the clinician must choose, with the patient, the most effective sequence of tests that provides the most information about diagnosis and staging, with the least risk. Careful consideration should be given before carrying out a test that only gives diagnostic pathology when information on staging is also needed to guide treatment.1,2


Investigations
The NICE guideline incorporates more specific recommendations on the use of diagnostic and staging tests that fit with the algorithm, including the need for samples that are sufficient to allow tumour sub-typing and the measurement of predictive markers that are essential if the correct systemic therapy is to be given now and when new treatments become available. Some of the recommendations are summarised below and should be read in conjunction with Figure 1 (see below):1,2

  • PET-CT and endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS)-guided needle biopsy should be available in every cancer network
  • Audits of the local test performance of EBUS, EUS, and non-ultrasound-guided transbronchial needle aspiration (TBNA) should be performed
  • As modern chemotherapy requires that tumours are accurately classified, diagnostic samples should be adequate to permit pathological sub-typing and measurement of predictive markers
  • Assessment of mediastinal lymph nodes requires a different approach if treatment depends on whether they are positive for lung cancer cells; the size and hence the probability of being malignant dictates which test is used:
    • Mediastinal nodes are considered significantly enlarged if they are ?10 mm short axis on CT
    • Neck ultrasound with biopsy is the first test if neck nodes are seen on CT
    • For lymph nodes that are 10–20 mm maximum short axis (intermediate probability of malignancy), there may be more difficulty in sampling them without ultrasound guidance, but this will depend on local expertise in non-guided TBNA; furthermore, clarification of likely involvement may be required
      prior to tissue sampling. Therefore there is the option for PET-CT, EBUS/EUS-guided TBNA, or non-ultrasound-guided TBNA to be the first test
    • Neck ultrasound or non-ultrasound-guided TBNA (during standard bronchoscopy) are the preferred options for nodes >20 mm maximum short axis on CT (high probability of malignancy).

Fitness
There are new recommendations on risk assessment for surgery and the need to be prepared to reconsider patients’ fitness after treatment of underlying medical conditions. A trimodal approach to the assessment of patients for surgery is recommended, which includes assessment of:

  • operative mortality:
    • Use of a global risk score, such as Thoracoscore, to estimate the risk of death should be considered if evaluating surgery as an option for patients with non-small-cell lung cancer (NSCLC). The patient should be informed of the risk before they provide consent for surgery
  • cardiovascular morbidity:
    • This can be minimised by early optimisation of treatment, avoidance of surgery within 30 days of myocardial infarction, seeking a cardiology opinion for active cardiac conditions (including stents) or three or more risk factors, and by considering revascularisation, if indicated, prior to surgery for lung cancer
  • likelihood of postoperative dyspnoea:
    • Spirometry (and transfer factor where breathlessness is disproportionate or there is other lung pathology) combined with segment counting should be used to estimate postoperative lung function. Shuttle-walk testing or cardiopulmonary exercise testing may be used to clarify risk of dyspnoea in borderline patients. Patients with postoperative values <30% may still be offered resection if they accept the risk of dyspnoea.
Figure 1: Diagnostic and staging clinical pathway 1,2

Diagnostic and staging clinical pathway Diagnostic and staging clinical pathway

CT=computed tomography; MDT=multidisciplinary team; PET=positron emission tomography; US=ultrasound; MRI=magnetic resonance imaging; EBUS=endobronchial ultrasound; EUS=endoscopic ultrasound; TBNA=transbronchial needle aspiration
National Institute for Health and Care Excellence (NICE) (2011) CG121. Lung cancer: The diagnosis and treatment of lung cancer. London: NICE. Reproduced with permission. Available at: www.nice.org.uk/guidance/CG121


Treatment modalities

A number of new recommendations have been made about surgery, radiotherapy, combination treatments, and therapy of small-cell lung cancer (SCLC) and are discussed below.

Treatment with curative intent

  • Open or thoracoscopic lobectomy should be offered as first-choice treatment to patients with NSCLC who are medically fit and suitable for treatment with curative intent. Lung parenchymal-sparing operations (segmentectomy or wedge resection) should be considered in patients with smaller tumours (T1a-b, N0, M0) and borderline fitness, and if a complete resection can be achieved1,2
  • Radical radiotherapy is indicated for patients with stage I, II, or III NSCLC who have good performance status (World Health Organization 0 or 1) and whose disease can be encompassed in a radiotherapy treatment volume without undue risk of normal tissue damage. Radiotherapy techniques have advanced considerably since publication of the 2005 NICE guideline and it is reasonable for centres to offer these techniques (including stereotactic body irradiation and 4-D planning) to patients. These treatments have the advantage of reducing the risk of damage to normal tissue (estimated by using measurements such as V20)1,2
  • All patients who are potentially suitable for multimodality treatment (surgery, radiotherapy, and chemotherapy in any combination) should be assessed by a thoracic oncologist and a thoracic surgeon1,2
  • Patients receiving radical radiotherapy should be part of a national quality assurance programme1,2
  • Combination treatment for patients with NSCLC offers the chance of improved outcomes from surgical treatment and better outcomes for non-surgical treatment. Thus chemoradiotherapy should be considered where surgical treatment is not possible.1,2

Assessment and treatment of SCLC

  • Healthcare professionals should arrange for patients with SCLC to receive an assessment by a thoracic oncologist within 1 week of deciding to recommend treatment. Patients with limited disease should be offered concurrent chemoradiotherapy or sequential chemoradiotherapy if this is not tolerated1,2
  • Surgery should be considered in patients with early-stage SCLC (T1-2a, N0, M0)1,2
  • Patients with extensive disease should be offered platinum-based combination chemotherapy if they are fit enough. Patients with relapsed disease should be offered second-line combination chemotherapy although there is little evidence of benefit if they have not responded to first-line treatment1,2
  • Prophylactic cranial irradiation should be offered to all patients with SCLC if their disease has not progressed on first-line treatment.1,2 If considering the use of topotecan, refer to Technology Appraisal (TA) 184.10

Management of endobronchial obstruction
There are now a variety of treatments for endobronchial obstruction (e.g. electrocautery, cryotherapy, stents, brachytherapy, thermoablation), which many patients may benefit from. The NICE guideline recommends that patients are monitored for endobronchial obstruction and that these techniques are made available to enable early treatment of such individuals.1,2

Chemotherapy for NSCLC was not reviewed owing to potential conflict with a number of single technology appraisals that were already published or in progress (TA162, TA181, and TA192).11–13

Implementation tools

NICE has developed the following tools to support implementation of Clinical Guideline 121 on Diagnosis and treatment of lung cancer. The tools are now available to download from the NICE website: www.nice.org.uk/CG121

Baseline assessment tool

The baseline assessment tool is an Excel spreadsheet that can be used by organisations to identify if they are in line with practice recommended in NICE guidance and to help them plan activity that will help them meet the recommendations.

Clinical audit report

Audit tools aim to assist organisations with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. They consist of audit criteria and data collection tool(s) and can be edited or adapted for local use.

Costing report

Costing reports are estimates of the national cost impact arising from implementation based on assumptions about current practice, and predictions of how it might change following implementation of the guideline.

Costing template

Costing templates are spreadsheets that allow individual NHS organisations and local health economies to estimate the costs of implementation taking into account local variation from the national estimates, and they quickly assess the impact the guideline may have on local budgets.

Slide set

The slides provide a framework for discussing the NICE guideline with a variety of audiences and can assist in local dissemination. This information does not supersede or replace the guidance itself.


Implementation

All healthcare professionals and patients should understand that a modern approach to early presentation, assessment, and treatment can improve survival and mortality in lung cancer. A nihilistic approach is not appropriate. In secondary care, this requires a dedicated multidisciplinary team that is keen to develop the expertise in diagnostics and therapeutics, and deliver a patient-centred service.

Approximately 40% of cancer-related 2-week wait referrals prove to have lung cancer,14 a proportion far higher than for breast or bowel cancer. The challenge in primary care is to refer more in the hope that some patients will be diagnosed earlier. In practice, this means that more patients should: have chest X-rays when they present with warning symptoms; and be referred where there is a high index of suspicion. Furthermore, in patients at increased risk (e.g. people over a certain age, current smokers, or with chronic obstructive pulmonary disease) there should be a willingness to repeat chest X-rays when symptoms change.

Conclusion

Lung cancer survival is beginning to improve and more patients are being offered potentially curative treatment such as surgical resection and new radiotherapy techniques. The challenge we face is to offer more patients these therapies by encouraging early presentation, prompt referral, expert diagnostic, staging, and fitness assessment, and ensuring that all patients have access to specialists who are willing to offer the latest treatments. Sadly there is likely to remain a majority of patients who will need palliative treatments and supportive care that is best provided by an integrated care approach.

  • Commissioners should ensure that primary care has access to radiology and smoking cessation services as prevention and early diagnosis of lung cancer are key responsibilities for GP practices
  • Commissioners will need to work with their local cancer network to ensure that NICE-recommended specialist services are available locally or at a tertiary centre
  • Specialist chemotherapy regimens should be agreed between commissioners and providers through cancer networks, and the costs specified in contracts
  • It is recommended that patients have access to a specialist lung cancer nurse and commissioners should ensure that such a post is complementary to primary and community services, including palliative care
  • Contracts should specify how chemotherapy and specialist nurse contacts are paid—there will be a new mandatory tariff for chemotherapy and external beam radiotherapy in 2012.a
  1. National Institute for Health and Care Excellence. The diagnosis and treatment of lung cancer (update). London: NICE, 2011. Available at: www.nice.org.uk/guidance/CG121/NICEGuidance/pdf/English
  2. National Collaborating Centre for Cancer. The diagnosis and treatment of lung cancer (update). London: NICE, 2011. Available at: www.nice.org.uk/guidance/CG121/Guidance
  3. Cancer research UK website. Cancer mortality—UK statistics. info.cancerresearchuk.org/cancerstats/mortality/ (accessed 1 December 2011)
  4. .Department of Health. Improving outcomes: a strategy for cancer. London: DH, 2011. Available at: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_123371
  5. Rich A, Tata L, Stanley R et al. Lung cancer in England: information from the National Lung Cancer Audit (LUCADA). Lung Cancer 2011: 72 (1): 16–22.
  6. NHS Information Centre. National lung cancer audit 2010. NHS Information Centre, 2010. Available at: www.ic.nhs.uk/services/national-clinical-audit-support-programme-ncasp/audit-reports/lung-cancer
  7. Coleman M, Forman D, Bryant H et al. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK (the International Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 2011; 377 (9760): 127–138.
  8. National Cancer Research Institute website. National Awareness and Early Diagnosis Initiative (NAEDI). www.ncri.org.uk/default.asp?s=1&p=5&ss=11 (accessed 15 November 2011).
  9. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ 2010; 340: b5569 doi:10.1136/bmj.b5569
  10. National Institute for Health and Care Excellence. Topotecan for the treatment of relapsed small-cell lung cancer. London: NICE, 2009. Available at: www.nice.org.uk/TA184
  11. National Institute for Health and Care Excellence. Erlotinib for the treatment of non-small-cell lung cancer. London: NICE, 2008. Available at: www.nice.org.uk/TA162
  12. National Institute for Health and Care Excellence. Pemetrexed for the first-line treatment of non-small-cell lung cancer. London: NICE, 2009. Available at: www.nice.org.uk/TA181
  13. National Institute for Health and Care Excellence. Gefitinib for the first-line treatment of locally advanced or metastatic non-small-cell lung cancer. London: NICE, 2010. Available at: www.nice.org.uk/TA192
  14. Lewis N, Le Jeune I, Baldwin D. Under utilisation of the 2-week wait initiative for lung cancer by primary care and its effect on the urgent referral pathway. Br J Cancer 2005; 93 (8): 905–908.G