Management of Unresected Stage III Non-small Cell Lung Cancer: A Systematic Review

PurposeTo conduct a systematic review to determine the most effective therapy for patients with unresected stage III non-small cell lung cancer.MethodsRelevant randomized trials and meta-analyses were identified through a systematic search of the literature.ResultsForty-seven trials and six meta-analyses were included. No statistically significant survival differences were detected for immediate versus delayed administration of radiotherapy or different doses of hyperfractionated radiotherapy. Three of 12 trials comparing various doses and schedules of radiotherapy detected a statistically significant survival advantage with higher radiation doses. All meta-analyses found a statistically significant survival advantage for chemoradiation, particularly platinum-based, compared with radiation alone. One meta-analysis and three trials comparing concurrent with sequential chemoradiation detected a statistically significant survival advantage with concurrent administration. Increased toxicities, especially esophagitis and hematologic events, were generally associated with concurrent chemoradiation. The survival advantage for concurrent platinum-based chemoradiation corresponds to a 4% absolute survival benefit at 2 years. With respect to trials comparing different chemotherapy regimens or schedules, there is insufficient evidence to determine which particular regimen or schedule is most effective.ConclusionPalliative radiotherapy can provide symptom relief for symptomatic patients with poor performance status. For patients with good performance status, chemoradiation improves survival compared with radiotherapy alone, particularly when the two modalities are administered concurrently. Sequential chemoradiation is a treatment option for borderline-status patients. Adequate assessment of performance status is important when evaluating treatment options for patients with unresected non-small cell lung cancer. Patients and physicians should have a full discussion of the benefits, limitations, and toxicities of therapy.