Value of accelerated multimodality therapy in stage IIIA and IIIB non-small cell lung cancer

Objectives: This study was undertaken to assess accelerated multimodality therapy in patients with IIIA and IIIB non-small cell lung cancer in terms of toxicity, feasibility, response, survival, and recurrence (value) and to identify predictors of pathologic response and improved survival. Methods: Between October 1994 and September 2000, a total of 105 patients with stage pIIIA (n = 78) or pIIIB (n = 27) non-small cell lung cancer were enrolled in a study of accelerated multimodality therapy, consisting of hyperfractionated radiotherapy with concurrent chemotherapy (paclitaxel and cisplatin) followed by resection and postoperative chemoradiation. Multivariable correlates of pathologic response and survival were assessed. Results: Toxic effects related to induction therapy necessitated hospitalization in 40% of patients (n = 42); treatment-related mortality was 9% (n = 9). With respect to feasibility, 100% of patients completed induction therapy, 93% (n = 98) of cancers were operable, 79% (n = 83) of cancers were curatively resectable, and 77% (n = 81) of patients completed all therapy. Sterilization of mediastinal nodes was similar (P = .6) for pN2 (35%) and pN3 (30%) disease. Median, 2-year, and 5-year survivals were 27 months, 53%, and 32%, respectively. Locoregional recurrence, distant recurrence, and both were seen in 6% (n = 6), 45% (n = 47), and 3% (n = 3) of patients, respectively. Pathologic response was not predictable. Nodal status predicted incrementally decreasing survival for patients with cancers down-staged to ypN0 or ypN1 (n = 35) versus ypN2 (n = 44) versus ypN3 (n = 20; P < .001). In addition, advancing age, squamous histologic type, and higher pT predicted poorer survival. Conclusions: Accelerated multimodality therapy is equally valuable in IIIA and IIIB non-small cell lung cancers. Despite unpredictable response to induction therapy, younger patients and those with nonsquamous histologic type, sterilization of mediastinal lymph nodes, and lower pT benefit most. A ypN2 stage reduces but does not preclude long-term survival.