Purpose: To improve understanding of what is adequate in local treatment of extremity soft tissue sarcomas (ESTS), to maximize the ratio between local control, limb preservation and prognosis. Patient and Methods: Nine hundred ninety-seven consecutive patients affected by primary ESTS were reviewed. Size, depth, histotype and grade of the tumor, margin status (R0, R1, R2) of surgical resection, and adjuvant treatments were analyzed. Univariable and multivariable analysis were carried out. For the subgroup of R1 resection the presence/absence of the tumor at the inked surface and the presence/absence of an anatomic barrier were also considered. Results: Five-and 10-year mortality estimates (95% confidence interval) were 0.29 (0.20-0.38) and 0.38 (0.28-0.49) in R1 cases, and 0.16 (0.13-0.19) and 0.19 (0.16-0.23) in R0 cases (P = 0.0003). Size, grade, depth, and histologic subtype were also significant predictor of mortality. Significant determinants for local relapse were surgical margins, radiation therapy, and histologic subtype. In the subset of R1 resections trends towards a better local control for R1 negative cases and histology other than myxofibrosarcoma were identified. Significant determinants for distant metastases were size, grade and histologic subtype of the tumor but not surgical margins. Conclusions: Quality of surgical margins independently predicted local control and survival. The effect on survival was directly mediated by local recurrence to proximal sites invading the abdomen/thorax, and this may indeed be the main way by which quality of surgery directly impacts the final prognosis of ESTS patients.
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