Advanced conventional chondrosarcomas: Time to revisit treatments and clinical research for what is not an indolent disease

Abstract

Medical and surgical oncologists involved in the management of patients with sarcoma know well that the management of patients with recurrent chondrosarcoma is quite challenging. However, until recently, the scientific community knew almost nothing at all about the real outcome and the respective impact of treatments on patients in this setting.In this issue of Cancer, van Maldegem and colleagues have reviewed the medical files of 171 patients from 2 European institutions with the hope of identifying the demographics, prognostic factors, and natural history of advanced conventional chondrosarcoma. 1 One of the main limitations of their study is that the patients were included because of "unresectability." Indeed, at least for patients with locoregional disease, the definition of unresectability may be different from 1 institution to another in relation to surgical expertise and experience and to the subjective approach of the risk-tobenefit ratio of chondrosarcoma resection for a given patient. However, because 74% of patients included in the study had visceral metastatic disease, this does not alter 1 of its main messages: advanced conventional chondrosarcoma is a devastating disease with a median overall survival of only 11 months.Unfortunately, the performance status of patients was not described in the study, and no reliable multivariate analysis was performed. However, 2 main prognostic factors seem to emerge from the data. The first 1 is the presence of distant metastasis. Although long survival has been reported in patients with local disease only (26% at 3 years), evidence suggests that the presence of distant metastatic disease is associated with a very poor outcome (<8% of survivors at 3 years). The other and probably more interesting result is the apparent benefit of antineoplastic treatment versus best supportive care. Indeed, patients managed with systemic treatment (mainly anthracycline-based chemotherapy) had an overall survival rate of 26% after 3 years compared with 8% for the patients who did not receive systemic treatment (P .05). Moreover patients with localized disease who received radiation therapy had improved survival compared with those managed with best supportive care only. These results obviously should be interpreted with caution, because retrospective series are inherently more susceptible to bias than controlled clinical trials. However, although data related to the role of radiotherapy are scarce, there are now several lines of evidence that contradict the commonly accepted assumption that chondrosarcomas are completely resistant to chemotherapy. A recent preclinical study has demonstrated that, although resistance to cisplatin is the rule, 2 some chondrosarcoma cell lines may display some sensitivity to doxorubicin. It is noteworthy that chondroid matrix does not hinder doxorubicin from entering the nuclei of the tumor cells. In a study that we recently reported, patients with conventional chondrosarcoma who were managed with chemotherapy (mainly anthracyclinebased) had an object...