PULMONARY METASTASES OF STAGE IIB EXTREMITY OSTEOSARCOMA AND SUBSEQUENT PULMONARY METASTASES

Purpose: This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis. Patients and Methods: We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected. Results: The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P <.001)and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P <.003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (greater than or equal to 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P <.001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P <.048), four or fewer recurrent pulmonary nodules (P <.047), unilateral pulmonary metastases (P <.037), or longer intervals between primary tumor resection and metastases (P <.082). Conclusion: Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed. (C) 1994 by American Society of Clinical Oncology.