Optimising Clinical Outcomes Following R1 Resection in Soft Tissue Sarcoma: An Evidence-Based Approach

Abstract

Soft tissue sarcomas (STS) are a heterogeneous group of mesenchymal malignancies for which complete surgical resection remains the cornerstone of curative treatment [ 1 , 2 ]. The quality of surgical margins is the single most important modifiable prognostic factor, with margin status independently predicting local recurrence (LR), distant metastasis-free survival (DMFS), and overall survival (OS) [ 3 ]. Analysis of margin classification systems in a cohort of 2,217 extremity and truncal STS patients demonstrated 10-year LR rates of 8% for R0, 21% for R1, and 44% for R2 resections, underscoring the stepwise increase in risk conferred by incomplete excision [ 4 ]. Positive margins have been associated with a nearly twofold increase in disease-specific mortality (HR 1.95), establishing margin adequacy as a central determinant of oncologic outcome [ 3 ]. However, achieving R0 resection in STS remains a significant clinical challenge. The anatomic complexity of many sarcoma sites, the proximity of tumours to critical neurovascular structures, and the frequent presentation of these rare tumours to non-specialist surgeons all contribute to suboptimal initial surgery. Particularly in the context of initially marginally resectable disease- where the inherent risk of an R1 margin is markedly elevated-intensive multimodal neoadjuvant strategies are increasingly necessitated to optimise surgical clearance [ 5 ]. A prospective phase 2 clinical trial (UNRESARC) evaluating preoperative hypofractionated RT (5 × 5 Gy) interdigitated with AI CHT demonstrated profound efficacy in this challenging demographic. Despite the presence of bulky, technically demanding tumours (median largest dimension 17.4 cm), this regimen facilitated en bloc R0 resections in 71.7% of patients, yielding an estimated 2-year LRFS of 67% and a 2-year DRFS of 57% [ 5 ]. Data from the French NETSARC nationwide registry demonstrated that only 36–47% of initial STS operations achieve R0 margins, with the higher figure reflecting improvements following implementation of a structured reference centre network [ 6 ]. A US National Cancer Database analysis of 25,406 extremity STS patients found that high-volume centres (≥ 20 cases/year) achieved significantly fewer positive margins than low-volume hospitals (12% vs. 17%, p < 0.001), with corresponding improvements in OS (HR 0.81, 95% CI 0.75–0.88) [ 7 , 8 ]. Similarly, the Spanish GEIS prospective registry reported 3-year OS of 82% at reference centres compared with 70.4% at local hospitals ( p = 0.003) [ 9 ]. A systematic review of 66 studies confirmed that specialist centre surgery is associated with higher negative margin rates, lower LR, greater limb conservation, and improved OS [ 10 ].