Does the addition of chemotherapy to neoadjuvant radiotherapy impact survival in high-risk extremity/trunk soft-tissue sarcoma?

Background The role of chemotherapy in extremity/trunk soft-tissue sarcoma (ET-STS) is controversial, even for patients at high risk for distant recurrence and death (those with high-grade tumors >= 5 cm in size). This study examines the impact of integrating chemotherapy with neoadjuvant radiotherapy (RT) on overall survival (OS) for patients with high-risk ET-STS. Methods The National Cancer Data Base was queried for adult patients with high-risk ET-STS who received neoadjuvant RT and limb salvage surgery between 2006 and 2014. Patients were stratified into RT and chemoradiotherapy (CRT) cohorts. OS for the RT and CRT cohorts was analyzed with the Kaplan-Meier method, log-rank tests, and Cox proportional hazards models. Propensity score matching (PSM) analysis was used to account for a potential treatment selection bias between the cohorts. Results A total of 884 patients were identified: 639 (72.3%) in the RT cohort and 245 (27.7%) in the CRT cohort. The unadjusted 5-year Kaplan-Meier OS rate was significantly higher in the CRT cohort: 72.0% versus 56.1% (P < .001). Neoadjuvant chemotherapy was associated with improved OS in univariate and multivariable analyses (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.41-0.78; P < .001). PSM identified 2 evenly matched cohorts of 212 patients each. The 5-year matched Kaplan-Meier OS rates were 69.8% and 55.4% for the CRT and RT cohorts, respectively (P = .002). The addition of neoadjuvant chemotherapy remained prognostic for OS on PSM (HR, 0.56; 95% CI, 0.39-0.83; P = .003). Conclusions The addition of chemotherapy to neoadjuvant RT was associated with improved OS for patients with high-risk ET-STS. In the absence of randomized data evaluating CRT versus RT, these findings warrant further investigation.