Adjuvant Chemotherapy in Localized Soft Tissue Sarcomas: Still Not Proven

Soft tissue sarcoma is a rare and heterogeneous group of tumors in terms of histological subtypes, molecular alterations, clinical presentation, and prognosis. Yet, these tumors are most often treated similarly in the localized phase. The standard treatment of these patients requires multidisciplinary management, in particular, careful diagnostic procedures and surgery by an expert physician, preceded or followed by external radiotherapy. The utility of adjuvant chemotherapy has been explored in 14 trials comparing adjuvant chemotherapy with no treatment. Several trials reported a lower risk for local relapse and lower risk for metastatic relapse, but only a few small trials reported longer overall survival. A meta-analysis of all trials failed to demonstrate a significant difference in the relapse-free survival (RFS) or overall survival rates. Two additional trials, reported afterward, presented conflicting results, with a significant benefit in terms of the RFS rate for the trial of the Italian Sarcoma Group, but no difference in the RFS or overall survival rate in the most recent European Organization for Research and Treatment of Cancer trial. We conclude that adjuvant chemotherapy has not been proven to improve the outcome of an unselected population of patients. Several hypotheses are proposed to account for this observation.