Treatment Strategies

Early Stage disease (stage I, II, IIIA)

For localised NSCLC patients who present with stage I and II disease, curative surgery is the preferred treatment option. Patients with stage IIIA NSCLC may be considered for surgery, although the percentage surviving at 5 years is approximately 23%.¹ However, even when diagnosed at the earliest stages, the cancer may have already begun to spread so that relapse rates range between 50% and 80% and the 5-year survival rate (i.e. the proportion of patients still alive 5 years after diagnosis) is between 24% and 61%. In theory, postoperative administration (i.e. adjuvant use) of chemotherapy or radiotherapy would be expected to reverse, or at least control the growth of micro-metastases, and so enhance the effectiveness of curative surgery.

A recent meta-analysis, which included more than 18,000 patients, suggested that postoperative radiotherapy has little effect on survival for patients with stage I/II NSCLC.19 This is perhaps unsurprising given that disease recurrence is located outside the chest in approximately 70% of cases, thus highlighting the major disadvantage of radiotherapy in this setting. The administration of high-dose irradiation to the whole body is obviously not desirable.

In contrast to radiotherapy, chemotherapy is a systemic treatment with the potential to be effective against the spread of the cancer to any part of the body. Apart from the toxicity issues surrounding conventional cytotoxic chemotherapies, which indiscriminately affect rapidly dividing cells, their introduction at an early point in the history of the tumour may promote drug resistance. In effect, this makes any further recurrence more difficult to treat without resorting to more frequent and aggressive drug regimens.

In cases of early-stage NSCLC that are considered to be operable (i.e. stages I, II and some IIIA) one or more courses of chemotherapy may be given before surgery (referred to as neoadjuvant or induction treatment) to provide the following advantages:

• Control of distant metastases
  
• Reduce risk of ‘seeding’ viable tumour cells during surgery
  
• Reduction of the tumour mass to increase the chances that the tumour can be fully resected
  
• Decreased incidence of positive margins (tumour cells in the surrounding tissue left after surgery)
  
• Less radical surgery may be required with greater potential for organ preservation.

The main disadvantage of neoadjuvant therapy is the delay to definitive surgery. If the tumour has not responded to initial chemotherapy, the patient’s disease may progress to a stage where the tumour becomes unresectable. Additionally, worsening pulmonary symptoms may also make the patient unsuitable for procedures under general anaesthetic.

Treatment Strategies

• Overview
• Early Stage
• Locally Advanced Stage
• Advanced Stage
• Future Strategies