Background: We already reported (Cancer 2012;118:5857) on better correlation of Choi criteria (Choi) than RECIST with the outcome of pts affected by high-risk STS entering a multicentric Italian/Spanish Phase 3 trial comparing 3 vs 5 cycles of (neo)adjuvant CT with full-dose epirubicin + ifosfamide (JCO 2012;30:850). We herein update these results with a longer FU. Methods: All pts were treated by 3 cycles of preop Epirubicin + Ifosfamide +/- RT. The diagnostic concordance between RECIST and Choi and their association with overall survival (OS) and freedom from progression (FFP) were assessed by a univariate Cox regression model. The prognostic value of histology was also investigated. Results: At a 115-mo (IQ range 102-129) median FU, in 243 evaluable pts (of 321 eligible pts), univariate Cox regression analysis confirmed the prognostic role of RECIST and Choi, and histology for both OS and/or FFP. Pts with leiomyosarcoma had the lowest PR rate, both those receiving preoperative CT alone and those receiving CT+RT. By contrast, undifferentiated pleomorphic sarcoma (UPS) had the highest response rate (whether receiving CT or CT+RT). Leiomyosarcoma and UPS were associated with the worst and best prognosis, respectively. Finally, in the subgroup of 69 pts treated with CT alone and evaluable by both Choi and RECIST criteria, Choi response was associated with a better OS (PD vs PR: HR = 5.27, 95%CI = 2.02-13.72; SD vs PR: HR = 2.40, 95%CI = 0.93-6.21), while RECIST did not (PD vs PR: HR = 2.21, 95%CI = 0.76-6.38; SD vs PR: HR = 0.56, 95%CI = 0.23-1.36). Conclusions: In this (neo)adjuvant trial, tumor response to CT + RT predicted a better outcome. Choi criteria were a better predictor than RECIST. Leiomyosarcoma fares worse than other histotypes. In an ongoing prospective trial in localized high-risk limb and trunk wall STS, perfusion/diffusion MR and PET are explored to assess tumor response, in addition to RECIST and Choi. Clinical trial information: 2004-003979-36.