As was noted earlier the prognosis for lung cancer is still bad, with little improvement in treatment success over the past twenty years. In the management of lung cancer, small cell lung cancer and non-small cell lung cancer are treated very differently, the stage of the disease is also important in deciding treatment options.

Non-small cell cancer does not show a good response to treatment with chemotherapy, thus the preferred treatment of choice is surgery, but results are poor in all but the most localised cancers. Radiation therapy can produce cure in a small minority of cases, and palliation in the majority of patients. Chemotherapy has shown to give modest improvement in survival in advanced stage disease⁵⁷, and can provide symptomatic relief.⁵⁸

There are two main issues to be taken into account when considering surgery for lung cancer; resectability and operability. A cancer is deemed to be resectable on the basis of its staging, taking into account invaded structures, presence of metastases and position. The operability refers to the patients’ ability to cope with both the operation and the subsequent reduction of lung volume and function. A pre-operative series of assessments is made to assess the patients’ overall medical condition and may include the patients’ pulmonary function, ventilation perfusion studies, cardiac function and exercise tolerance tests. As many lung cancer patients are smokers, they often have other medical conditions and poor respiratory function. In borderline operability, pre-operative physiotherapy to clear secretions may improve lung function. The type of resection that is carried out depends on the location and size of the cancer. Lobectomy is the removal of an entire lobe, segmentectomy is the removal of a bronchopulmonary segment, wedge resection is used for small peripheral tumours removing a large wedge of lung tissue, and sleeve resection is used for cancers involving the main bronchus. These operations are usually carried out using open techniques, but a video assisted operation (VAT) is used in some centres and is used in the Glenfield Hospital in Leicester. The standard open posterolateral thoracotomy is carried out with incision below the inferior angle of the scapula and division of the latissimus dorsi. The chest is entered through the bed of the unresected fifth or sixth ribs.⁵⁹ The advantage of the VATS operation is that it is less traumatic to the patient, cutting less tissue and having a lower associated decrease in lung function postoperatively.

The following recommendations for treatment are based on guidelines produced by the National Cancer Institute:⁶⁰

Stage 0 NSCLC can be treated with surgical resection, or alternatively with endoscopic phototherapy in some patients, though efficacy is yet to be proven.⁶¹

Surgery is the treatment of choice for patients with stage IA and IB NSCLC. Inoperable patients may be given radiotherapy in an attempt to cure, this is associated with a modest increase in 5-year survival.⁶² Patients who have undergone resection should be considered for trial chemotherapy to combat the occurrence of metastases, though currently adjuvant radiotherapy is associated with a worsened survival rate.⁶³

Stage IIA and IIB NSCLC should be treated similarly to Stage IA and IB NSCLC with surgery, radiotherapy with curative intent, clinical trials of adjuvant chemotherapy and radiotherapy following surgery. Again careful pre-operative assessment of the patient must be undertaken before surgery.

In patients with stage IIIA NSCLC the prognosis is poor, however there is a long term survival benefit in 5% to 10% of patients with radiotherapy.⁶⁴ Patients who require a thoracotomy to prove the presence of non-resectable disease and those with excellent performance status should be considered for clinical trials. Such trials examining fractionation schedules, endobronchial laser therapy, brachytherapy, and combinations of treatment modalities may improve survival in this category.⁶⁵ Surgery alone is indicated in a very select number of cases, with postoperative radiotherapy likely to improve local control.

Tumours in the superior sulcus often cause problems due to local invasion and have a reduced tendency for distant metastases. Local therapy for such tumours is therefore more likely to achieve cure. Surgery and radiotherapy separately or in various combinations may be curative in some patients.⁶⁶ Tumours directly invading the chest wall can often be cured with surgery alone.⁶⁷

Stage IIIB are best managed with chemotherapy and radiotherapy alone or in combinations depending on tumour site and performance status. Most patients with good performance are treated with combinations and this can lead to a 10% reduction in the risk of death compared with radiotherapy alone.⁵⁷ Patients with poor performance status are candidates for palliative radiotherapy.

Stage IV patients are suitable for palliative relief of local symptoms by radiotherapy. Treatment may be deferred in carefully monitored asymptomatic patients. Chemotherapy can be offered to patients, though it is of limited benefit and has serious risks and side effects. There are many combination regimens associated with a similar outcome :

Participation in clinical trials should be encouraged where appropriate. Endobronchial laser therapy and or brachytherapy may be used for obstructing lesions.

The following recommendations for treatment are based on guidelines produced by the National Cancer Institute⁶⁸ and Mayo Clinic⁶⁹

Staging and histological classification of the tumour are again important factors in determining the cause of best treatment. Because occult or overt metastatic disease is present at diagnosis in most patients, survival is little affected by small differences in stage. Hence, in the practical management of patients with Small Cell lung cancer, the complicated TNM system described earlier is not used, and the most useful distinction is between extensive and limited stage disease.⁷⁰ Though these terms are poorly defined, limited stage disease is thought of as cancer confined to the hemithorax of origin, the mediastinum and the supraclavicular nodes. Extensive stage disease means tumour that is too widespread to be included within the definition of limited stage disease above, and patients with distant metastases are always included in this group.

Limited stage disease is present in only one third of patients at diagnosis. Chemotherapy is the mainstay of treatment for limited stage SCLC.

The cytotoxic substances used in chemotherapy act on different stages in the process of cell division. For example: vincristine inhibits the formation of microtubules preventing spindle formation, doxorubicin inhibits DNA and RNA synthesis. These drugs, targeting the process of cell division, thus have a greater effect on cells that are rapidly dividing than those that are not. As cancers are rapidly dividing, they are affected more than normal cells. This activity also accounts for side effects such as alopecia and myelosuppression caused by such drugs.

In patients who achieve complete remission there is a risk of developing CNS involvement 2 years after treatment of between 35% and 65%.^71,72 Therefore patients who achieve such remissions are often offered prophylactic cranial irradiation (PCI), there are neurologic toxic effects of PCI and future studies are needed to show a definite survival benefit.

Treatment Options:

1. Combination chemotherapy with one of the following regimens and chest irradiation may be given.

• EC: Etoposide + cisplatin + 4000-4500 cGy chest radiation therapy

• ECV: etoposide + cisplatin + vincristine + 4500cGy chest radiation therapy

1. Combination Chemotherapy (with or without PCI) especially in patients with impaired pulmonary function or poor performance status.
2. Surgical resection followed by chemotherapy or chemotherapy plus chest irradiation (with or without PCI) for patients in highly selected cases.

Research is currently being carried out into new drug regimens, variations of doses, surgical resection of primary tumours, new radiation therapy schedules and techniques and timing of thoracic radiation. Work is also being carried out into the use of immunotherapy in the treatment of both NSCLC and SCLC, though no benefit has yet been shown. High dose chemotherapy with autologous bone marrow transplantation has been under investigation for several years, but little evidence of increased survival benefit has been produced. As the biology of small cell lung cancer is greater understood it is possible that new agents will be found; autocrine growth factors and their receptors and interferons are the subject of continuing research.

The poor survival of lung cancer patients, and the need for new approaches to therapy has led to a large number of patients being included in trials of experimental and unproven drugs. In my opinion it is very important to take into consideration the ethical issues of using unproven drugs and possibly causing more pain and discomfort to the patient before recommending experimental treatments.

Chemotherapy regimens similar to those used in limited disease are used in extensive disease, thoracic irradiation is seldom used because of the presence of metastatic disease.

Treatment Options:

1. Combination chemotherapy with one of the following regimens with or without PCI are well reported and have been shown to have similar survival benefits.

• CAV: cyclophosphamide + adriamycin + vincristine
• CAE: cyclophosphamide + adriamycin + etoposide
• EP or EC: etoposide + cisplatin or carboplatin
• ICE: ifosfamide + carboplatin + etoposide

1. Radiotherapy to sites of metastatic disease unlikely to be immediately palliated by chemotherapy, especially brain, epidural and bone metastases.
2. Second line therapy can achieve a survival benefit in pat--ients with recurrences.

Research into the taxanes (paclitaxel, docataxel), topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine, and gemcitibine as new agents is currently being undertaken and their integration into new regimens may prove beneficial. Clinical evaluation of variation in dose intensity, alternative drug schedules and high dose chemotherapy is also being undertaken.

Chemoprevention is intended to prevent the development of cancer in high-risk patients either with or without previous cancer histories. Trials of primary prevention in patients with no cancer history have shown no benefit of beta-carotene or Vitamin A.^73,74 Trials with Vitamin A⁷⁵, beta-carotene isotretinoin⁷⁶ have shown reduction in the incidence of second primary tumours but more results are awaited.

Given the poor survival in people with lung cancer, palliative care is of great importance. Patients needs vary greatly and arise from many different aspects of their illness, treatment and social situation. Problem areas include; physical symptoms, emotional problems, social factors, spiritual issues, and family or carer issues.⁷⁷

Palliative treatment for patients’ symptoms with recurrent NSCLC or SCLC consists of well managed analgesia, supplemental oxygen therapy and palliative radiotherapy. Procedures such as bronchoscopic laser therapy, brachytherapy and the placing of surgical stents may provide good symptomatic control in patients with obstructive lesions.

Counselling services, provided by specialist cancer nurses, such as the Macmillan Nurses is often invaluable in helping patients and families through this difficult time. Patients with decreased exercise tolerance, either as a result of their illness or treatment, may need specialist home care arrangements and it is important that a multi agency approach is taken with involvement of hospital and community teams.

The provision of palliative and terminal care in Leicestershire is provided through several hospices and palliative care suites in community hospitals. The care of such patients should involve specially trained staff and a palliative care physician should be available for consultation.

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