Epidemiology

Lung cancer is the second most common tumour of both men and women in the United Kingdom (Figure 26.1). The overall prospects for survival are poor: fewer than 10% of patients survive 5 years from diagnosis (Table 26.1). In the United Kingdom, there were 43,463 new diagnoses and 35,184 deaths from lung cancer in 2011.

Smoking and prevention

At present there are 10 million smokers in the United Kingdom having declined from a peak in the mid 1970s. In 1974, there were 10 cigarettes smoked each day per adult male and 5 cigarettes smoked per day per adult woman in the United Kingdom (Figure 26.2). One in two regular smokers will eventually be killed by the habit and half of them will die before the age of 70. The link between smoking and lung cancer was established 50 years ago and since then 6.5 million people have died in the United Kingdom because of tobacco-related disease (Figure 26.3).

The Department of Health has adopted six strategies to try and reduce the deaths from smoking:

• Reducing exposure to environmental tobacco smoke
  
• Educating people on risks of smoking
  
• Increasing taxation on tobacco products
  
• Limiting tobacco advertising and promotion
  
• Regulating tobacco products
  
• Providing assistance for individuals to quit smoking

Examples of these strategies include the introduction of smoke-free legislation in 2007 and public education through graphic television anti-smoking advertisements. Raising duty on cigarette sales also reduces consumption; a 10% price rise reduces consumption by 4%. However, this is undermined by increasing levels of tobacco smuggling, which is estimated to account for 16% of the current UK cigarette market. Tobacco advertising promotion and sponsorship is banned in the United Kingdom and plain packaging of cigarettes should be introduced in 2015, unless the government makes another U-turn on this policy.

Public policy on smoking has been led by a complex cost–revenue balance. It is said that if all smoking ceased, the loss of revenue from tobacco taxation coupled to increases in pension payments because of reduced mortality would bankrupt UK Plc. Others argue that the revenue generated by smoking pays for the cost of care to the NHS of smoking-related illness. These are not great arguments.

In 1999, an NHS stop smoking service was established. In addition to encouragement advice and avoidance strategies, most clients are provided with pharmacological support: usually nicotine replacement therapy, bupropion or varenicline. Nicotine replacement therapy is meant to be used for a short length of time with gradual tapering off of the dose. It is available as transdermal patches, gum, lozenges, sprays and inhalers. Nicotine replacement therapy increases the chances of stopping smoking by 50% compared to placebo but the vast majority of over-the-counter users will relapse within 6 months.

The antidepressant bupropion (Zyban) reduces nicotine craving and is generally used for 12 weeks with advice to stop smoking 10 days into the course. The most important side effect is epileptic seizures and both headaches and insomnia are common. Bupropion is about as effective as nicotine replacement therapy but fewer people will return to smoking after completing the course. Varenicline (Champix) is a partial nicotinic acetylcholine receptor agonist that reduces both craving and enjoyment of tobacco. It causes nausea and less frequently neuropsychiatric disturbances. It is more likely to result in smoking cessation, with a 1-year complete abstention rate of 23%. Despite all these efforts and advances, the rate of decline in smoking in the United Kingdom is only 0.4% per year.

Pathogenesis

Screening

Presentation

Patients with lung cancer generally present with a cough or haemoptysis. This may be associated with weight loss and symptoms of metastatic cancer (Box 2.2(e)), such as bone pain (Figure 26.4) or jaundice. Patients with symptoms suggestive of lung cancer should be referred promptly by their general practitioner to a specialist chest physician. One of the concerns of oncologists in the 1990s was the lack of referral on from specialist chest physicians to oncologists, with patients regarded somewhat as property. One of the major changes that we have seen in the third millennium has come about as a consequence of the central promotion of the philosophy of the multidisciplinary team. As a result, there is multispecialty input into the management of lung cancer patients and it is the view of these authors that the care of lung cancer patients has generally improved throughout the country.

The signs of lung cancer are many and of particular interest is the observation of clubbing of the fingers occurring in squamous cell lung cancer. The aetiology of finger clubbing, which is associated with hypertrophic osteoarthropathy and polyarthralgias, has been postulated as including the secretion of parathormone (PTH) by tumours and also, more recently, the ectopic secretion of platelet-derived growth factor (see Figures 39.6 and 39.7). Other clinical abnormalities may include Horner’s syndrome (Figure 26.5) or hoarseness, which are pointers to inoperability as a result of nerve entrapment by the tumour of the sympathetic chain and recurrent laryngeal nerves, respectively. Dysphagia may occur as a result of mediastinal lymph node enlargement. Paraneoplastic syndromes are commonly associated with lung cancer, particularly the small cell carcinoma variant. These include cutaneous syndromes of dermatomyositis and acanthosis nigricans, the neurological complications of peripheral neuropathy, cerebellar ataxia and the Eaton–Lambert syndrome (see Chapter 39). The endocrine features of ectopic PTH, adrenocorticotrophic hormone (ACTH) and antidiuretic hormone (ADH) secretion are all spectacular in their presentations.

Investigations should include a full blood count, liver function tests, chest X-ray (Figure 26.6) and sputum cytology. Bronchoscopy is organized and should proceed within a few days (Figure 26.7). Biopsies and washings are then obtained and examined microscopically. By these means, a histological diagnosis will be achieved. Diagnosis may not be achieved in the context of peripheral lesions and if this is the case, then needle biopsies under CT scanning or fluoroscopic imaging should be arranged (see also Figures 2.6, 40.1, 40.2, 40.3, 40.4, 40.5, 40.6b, 40.10 and 40.11).

Pathology

Staging and grading

Treatment

Treatment of non-small cell lung cancer

Non-small cell lung cancer may be treated with either surgery or with radiation treatment. Surgery is only possible for patients with limited stage disease; that is, T1N0M0 and T2N0M0 disease, and a small number with T2N1M0 tumours. There is increasing surgical enthusiasm for operating on more extensive tumours, and it is not uncommon to find patients with T3 disease proceeding to surgery. However, the results of this approach are usually poor. The increasing use of CT–PET scanning prior to surgery provides more accurate tumour staging and has reduced the number of patients undergoing “open and shut” thoracotomies for inoperable tumours.

The United Kingdom falls below the European average in terms of the number of people proceeding to surgery because of issues of resource availability in terms of scans and surgeons. Surgery has a significant morbidity and mortality, and operability depends upon lung function prior to resection, together with cardiac status and the presence of other major illnesses. It is estimated that approximately 30% of patients with non-small cell carcinoma of the lung have operable tumours. The 5-year survival for this group of patients is variably quoted at between 5% and 40%. A review of 2675 patients gave a five-year survival of 30%. There is a subgroup variation in survival, depending upon pathological staging and histology. For example, if those operable patients with adenocarcinoma are considered, the expectation for survival ranges between 38% and 79% and averages 65% at 5 years. If, on the other hand, operable patients under 40 years of age are considered, survival rises to 70%.

Radical radiotherapy, that is, radiotherapy given with curative intent, is considered for those patients who have inoperable disease by virtue of a poor medical state rather than spread of the cancer. Five-year survival figures of 6% were reported in a review of 1487 patients. Conventionally, patients receive 6000cGy over a 6-week period. More rapid treatment regimens are used, particularly in the north of England, and similar survival figures are found. For the majority of patients with more advanced cancer, radiotherapy is only used to palliative symptoms, which might include haemoptyses, breathlessness or chest pain. Radiotherapy is given according to various prescriptions; some radiotherapists advise a single dose of 1000–1500 cGy, others 3000 cGy in 10 fractions over 2 weeks. Radiotherapy, too, has side effects, and these include tiredness, oesophagitis and skin changes.

There is an increasing role for chemotherapy in the management of lung cancer, both as adjuvant therapy following surgery, neoadjuvant treatment prior to surgery, in combination with radiotherapy in stage III disease and as palliative therapy for advanced disease. The optimum treatment for advanced lung cancer depends upon the histological classification (nonsquamous or squamous) and the presence of driver mutations of genes such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) for which specific inhibitors are available. This approach has been rather grandly named “personalized genotype directed therapy”. In general in the absence of a specific mutation, chemotherapy is given as a doublet of two drugs, one of which is permetrexed and cisplatin if the tumour is nonsquamous. For tumours harbouring activating mutations of EGFR, oral tyrosine kinase inhibitors such as erlotinib and gefitinib are indicated as first-line therapy. Side effects are reported, the most common of which is an erythematous skin reaction, and the occurrence of this rash seems to be associated with tumour responsiveness. Tumours with an ALK fusion oncogene may be treated with crizotinib, an oral tyrosine kinase inhibitor that targets ALK. What was once a Cinderella disease waiting for her prince has now emerged from the shadows with the availability of several new drugs of promise to be bestowed upon her, provided her dowry is bountiful, as the cost of these new drugs is considerable.