Research in context
Evidence before this study
We searched PubMed for all randomised trials that involved adjuvant or neoadjuvant chemotherapy in localised soft tissue sarcoma, published in English between Jan 1, 1980, and Dec 30, 2016. We used the following search terms: “soft tissue”, “sarcoma”, “adjuvant chemotherapy”, “neoadjuvant chemotherapy”, “anthracycline”, “Ifosfamide”, “randomized”, and “trial”. We identified 20 randomised phase 3 clinical trials on adjuvant chemotherapy, one phase 2 clinical trial on neoadjuvant chemotherapy, and two meta-analyses. Results of the trials are conflicting, with negative results from the largest studies and positive results from the smaller ones.
Added value of this study
Formally, this is a negative trial because it does not show any advantage of histotype-tailored chemotherapy over standard chemotherapy in resectable high-risk soft-tissue sarcoma of the extremities or trunk wall. However, the observation of a statistically significant and clinically relevant difference in disease-free survival and overall survival at 3 years averaging 20% in favour of standard chemotherapy over the histotype-tailored neoadjuvant chemotherapy group, represents new data in support of the efficacy of neoadjuvant standard chemotherapy.
Implications of all the available evidence
Available evidence on the efficacy of neoadjuvant chemotherapy is conflicting, but available clinical practice guidelines regard this approach as an option that can be proposed to the patient in conditions of uncertainty for shared decision making. Although we await the amended final analysis of this trial, the data provided so far support a short chemotherapy regimen of full-dose anthracycline plus ifosfamide neoadjuvant in patients with high-risk localised soft-tissue sarcoma of the extremities and trunk wall.