Abstract BACKGROUND: For patients who have chondrosarcoma with unresectable disease, because of tumor location, tumor size, or extensive metastatic disease, treatment options are very limited because of their relative resistance to radiotherapy and chemotherapy. The overall survival of this patient population is poor; however, specific studies are lacking, and large series have not been published. Therefore, the authors conducted this retrospective, 2-center study to gain insight into the outcome of patients with advanced, unresectable, conventional central chondrosarcoma. METHODS: All patients with unresectable conventional central chondrosarcoma who were diagnosed between January 1, 1980 and December 31, 2011 in 2 major European bone sarcoma centers (Rizzoli Institute, Bologna, Italy and Leiden University Medical Center, Leiden, the Netherlands) were selected. Relevant information was collected from the medical records at both centers. RESULTS: In total, 171 patients met the selection criteria. The overall survival rate for all patients was 48% at 1 year, 24% at 2 years, 12% at 3 years, 6% at 4 years, and 2% at 5 years. Patients with unresectable, locally advanced disease without distant metastases had a significantly better survival than patients with metastatic disease (P = .0014). Systemic treatment, consisting of either doxorubicin-based chemotherapy or the noncytotoxic drugs imatinib and sirolimus, improved survival significantly compared with no treatment (P = .0487). For patients who had locally advanced disease without metastases, radiotherapy was associated with a survival benefit (P = .0032). CONCLUSIONS: This study provides a standard for overall survival rates after a diagnosis of unresectable conventional central chondrosarcoma. Systemic treatment and radiotherapy may improve survival, although selection bias because of the retrospective nature of this study may have influenced the outcome. The poor survival underlines the need for new therapeutic options for this patient population. Cancer 2014. © 2014 American Cancer Society. © 2014 American Cancer Society.