Multimodality therapy of patients with stage IIIA, N2 non-small-cell lung cancer. Impact of preoperative chemotherapy on resectability and downstaging

To assess the effect of neoadjuvant platinum-based chemotherapy on resectability, stage of disease at resection, and patterns of recurrence and survival in patients with IIIA, N2 non-small-cell lung cancer, we examined the first 60 patients treated with neoadjuvant chemotherapy followed by attempted resection in our institution. Of 67 patients identified, 7 patients were ineligible because of comorbidities, 3 patients refused chemotherapy, and 1 consented but died before treatment. Fifty-six received neoadjuvant chemotherapy. Complications of chemotherapy were minor, with no deaths. Fifty-four patients had thoracotomy; 75% (n = 42) had complete resection and 25% (n = 14) had unresectable lesions. One postoperative death occurred (2%). Pathologic review of specimens and nodal groups revealed that 41% (n = 23) were downstaged, 39% (n = 22) remained stage IIIA, and 19% (n = 11) progressed. Squamous histologic type was predictive of resectability, 18 of 20 patients having resectable squamous cell tumors (p < 0.05). Actuarial survivals at 1 and 2 years were 74% and 52%, respectively. In patients with resectable tumors survivals at 1 and 2 years were 85% and 67%, respectively. For those with unresectable lesions, survivals were 43% and 14%. Relapse-free survivals at 1 and 2 years for patients with resectable lesions were 70% and 42%, respectively. Relapses were local in 25% (n = 4), at a distant site only in 50% (n = 8), combined local and distant in 25% (n = 4). Distant relapse occurred in the central nervous system only in 7 of 8 patients (88%). Complete resectability was highly predictive of improved survival (p < 0.0002). Weight loss did not affect resectability but was associated with decreased survival (p < 0.003). Neoadjuvant chemotherapy appears to improve resectability and to pathologically downstage N2 non-small-cell lung cancer from stage IIIA. Multiinstitutional randomized trials are needed to further demonstrate the efficacy of this approach.