Five-year results of a randomized phase III trial of pre-operative vs post-operative radiotherapy in extremity soft tissue sarcoma

9007 Background: In the limb preservation approach to soft tissue sarcoma (STS), controversy exists about whether pre-operative (pre-op) or post-operative (post-op) radiotherapy is the preferred external beam radiotherapy (EBRT) strategy. Preliminary analysis of a randomized phase III trial undertaken from 1994–97 that compared pre-op (50 Gy / 25 fractions) vs post-op (66 Gy / 33 fractions) showed greater wound complications confined to the lower limb with pre-op, greater late fibrosis and limb edema with post-op, and potentially different disease-specific outcomes. The purpose here is to report 5-year disease-specific outcomes in this trial. Methods: The trial was originally powered to address the incidence of wound complication four months following protocol treatment. Secondary end-points included disease control, late toxicity and function. The randomization process included stratification by tumor size dichotomized at 10 cm. Actuarial methods were used to assess disease-specific outcomes and followed the 'intention to treat' principle. Cox proportional hazards models were used to adjust for potential predictive factors. Results: One hundred and ninety patient were randomized (94 to pre-op and 96 to post-op) with median follow-up of 6.9 years. Demographics were equally balanced between both arms. The 5-year results for pre-op vs post-op respectively were, local control: 93% vs 92%; metastatic-relapse free: 67% vs 69%; recurrence-free survival: 58% vs 59%; overall survival: 73% vs 67% (P=0.48); cause specific survival: 78% vs. 73% (P=0.64). Cox modeling showed only resection margins as significant for local control. Tumor size and grade were the only significant factors for metastatic-relapse, overall survival and cause specific survival. Grade was the only consistent predictor of recurrence-free survival. Conclusions: Pre-op and post-op EBRT are equally effective in achieving control and survival in extremity STS. Because the normal tissue complication profile differs for both approaches, anatomic site should be considered in the choice of EBRT approach. No significant financial relationships to disclose.