Unresected stage III non-small-cell lung cancer. Provincial Lung Cancer Disease Site Group

1) What is the role of different schedules or doses of radiotherapy in patients with unresected, clinical or pathological, stage III non-small-cell lung cancer (NSCLC)? 2) Does chemotherapy combined with radiotherapy provide improved survival compared with radiotherapy alone in patients with unresected NSCLC?

To make recommendations about the role of chemotherapy and radiotherapy in the treatment of unresected stage III NSCLC.

Survival is the primary outcome of interest. Quality of life is a secondary outcome.

Evidence was selected and reviewed by 5 members of the Provincial Lung Cancer Disease Site Group (Lung DSG) of the Ontario Cancer Treatment Practice Guidelines Initiative. The Lung DSG comprises medical and radiation oncologists, pathologists, surgeons, epidemiologists, a psychologist and a medical sociologist. No community representative participated in the development of this guideline.

Two meta-analyses were available for review. The specific analysis of interest examined the role of combined chemotherapy plus radiotherapy v. radiotherapy alone in locally advanced disease. The first meta-analysis included combined data from 22 randomized controlled (RCTs) involving a total of 3033 patients. The second included combined data from 14 RCTs involving a total of 2589 patients. Also reviewed were 4 RCTs of radiotherapy alone, 1 trial of combined chemotherapy and radiotherapy that was not included in the meta-analysis, 4 abstracts of studies of combined chemotherapy and radiotherapy, and 4 trials examining the role of hyperfractionated radiotherapy.

In the first meta-analysis, an overall benefit was detected at 2 years for the use of combined chemotherapy and radiotherapy. A hazard ratio of 0.90 (p = 0.006), or a 10% reduction in the risk of death, translated into an absolute benefit of 3% at 2 years and 2% at 5 years. A subgroup analysis of cisplatin-based chemotherapy plus radiotherapy versus radiotherapy alone demonstrated a 13% reduction in the risk of death in the combined treatment arm (pooled hazard ratio 0.87, 95% confidence interval [CI] 0.79-0.96), for an absolute benefit of 4% at 2 years. In the second meta-analysis, there was a 13% reduction in the risk of death in the combined therapy arm at 2 years (pooled relative risk [RR] 0.87, 95% CI 0.81-0.94) and a 17% reduction at 3 years (pooled RR 0.83, 95% CI 0.77-0.90). Subgroup analysis of cisplatin-based chemotherapy plus radiotherapy versus radiotherapy alone showed similar results: a 15% reduction in the risk of death in the combined therapy arm at 2 years (pooled RR 0.85, 95% CI 0.79-0.92) and a 19% reduction at 3 years (pooled RR 0.81, 95% CI 0.74-0.88).

For patients with unresected stage III NSCLC, the combination of cisplatin-based chemotherapy and radical radiotherapy provides a survival benefit compared with radiotherapy alone. This guideline is based on high-quality evidence from 2 meta-analyses of RCTs. Patients with good performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) and minimal weight loss (less than 5% in the preceding 3 months) have been shown to have a survival benefit from treatment with combined chemotherapy and radiotherapy and should be considered for this type of treatment approach (see section V). For these patients, thoracic irradiation of 60 Gy in 30 fractions over 6 weeks, in combination with cisplatin-based chemotherapy, should be recommended as a treatment option. The patient and physician should discuss fully the benefits, limitations and toxic effects of therapy. Patients not meeting these criteria are not candidates for combined therapy; those experiencing symptoms amenable to treatment should receive palliative thoracic irradiation. At this time, hyperfractionated radiotherapy is not recommended outside of the context of a clinical trial. (ABSTRACT TRUNCATED)