Over the past 30 years, there has been a migration away from amputation and radical ablative surgical procedures and toward more conservative, function-preserving surgery combined with radiation to treat extremity and body wall soft-tissue sarcomas. Efforts are now being focused on optimizing and streamlining treatment, including identifying subpopulations of patients who may be adequately treated by surgery alone. The goal of these efforts is to minimize the risks for short- and long-term treatment-related morbidity while maintaining excellent rates of local tumor control. This report will briefly review the progress made in these areas.
The primary therapy for most (but not all) patients with localized soft-tissue sarcoma is surgical resection plus radiation. The evidence base for this treatment approach comes from two small, single-institution, randomized trials that demonstrated improved local control (but not survival) with surgery plus radiation.[1,2] On the basis of these two trials, a general standard of care for patients with localized sarcomas has evolved that includes surgery and radiation.
Optimal Treatment Sequence
Considerable attention has been focused on the optimal sequence of surgery and radiation. This is because both pre- and postoperative radiation offer specific advantages but are associated with specific risks (Table 1). Preoperative radiation generally is administered using a lower total dose (50 Gy) and smaller treatment volume than postoperative radiation (65 Gy). These differences are clinically significant since the lower dose and smaller treatment volume used with preoperative radiation result in lower risks for serious late treatment-related adverse effects including edema and fibrosis. However, the risks for short-term side effects—particularly radiation-related impairment in wound healing leading to major wound complications—is higher with preoperative radiation than postoperative radiation. Because the local control rates with these two approaches appear similar, assessment of the risks for these clinically significant short- and long-term side effects assumes considerable importance in individual patient treatment planning.
The single best evidence source evaluating treatment sequencing comes from the Canadian Sarcoma Group's SR2 randomized trial of pre- vs postoperative radiation. This trial randomly assigned patients with localized primary or recurrent extremity sarcomas to be treated using external-beam radiation (50 Gy with a 16-Gy boost for microscopically positive surgical margins) followed by surgery, or surgery followed by external-beam radiation (66 Gy). The primary endpoint was wound complications; a number of clinically relevant secondary endpoints were also evaluated, including late complications and quality-of-life issues.
Radiation-associated wound complications were more common in patients receiving preoperative radiation—a 33% wound complication rate in the preoperative radiation arm vs 16% in the postoperative radiation arm. However, late (generally irreversible) tissue effects including fibrosis and edema were more common following postoperative radiation. This was related to the higher radiation dose and larger field size required for postoperative radiation. Other late complications including second malignancies will presumably be reported when additional patient follow-up is available.
The results of the SR2 trial also suggest that local anatomic factors including tumor size and anatomic location should be considered in determining the optimal treatment sequence for a given patient. For example, patients with an upper-extremity tumor should be considered for preoperative radiation given the low risk for radiation-associated wound complications and low risk for treatment-related edema and fibrosis associated with preoperative radiation in this group. However, in patients with lower-extremity sarcomas, particularly those located in the upper thigh, where wound complications were most frequent in the SR2 study, postoperative radiation might be a better choice. In either case, patients should be counseled regarding the complex issues involved.