Background
Randomized trial (Princess Margaret Hospital/Canadian Sarcoma Group) comparing preoperative vs. postoperative external beam RT for soft tissue sarcoma of the limbs. 190 patients (94 pre-op, 96 post-op). Pre-op RT: 50 Gy in 25 fractions. Post-op RT: 66 Gy in 33 fractions. Primary endpoint: wound complication rate within 120 days of surgery.
Interventions and follow up
Arm A: Preoperative RT — 50 Gy in 25 fractions, then surgery
Arm B: Postoperative RT — surgery, then 66 Gy in 33 fractio
Primary endpoint: Wound complications within 120 days of surgery
mFollow up: 3.3 years (median)
Arm B: Postoperative RT — surgery, then 66 Gy in 33 fractio
Primary endpoint: Wound complications within 120 days of surgery
mFollow up: 3.3 years (median)
Results
Wound Complications (primary): Pre-op 35% vs. post-op 17%, P=.01
OS: Slightly better with pre-op RT, P=.0481
Local Control: Comparable between arms (no significant difference)
Late toxicity: Post-op RT associated with greater long-term fibrosis, edema, joint stiffness
OS: Slightly better with pre-op RT, P=.0481
Local Control: Comparable between arms (no significant difference)
Late toxicity: Post-op RT associated with greater long-term fibrosis, edema, joint stiffness
Adverse events
Main adverse events: Pre-op RT: significantly higher wound complication rate (35%); pre-op arm had more lower-extremity tumors (higher-risk site). Post-op RT: less acute wound morbidity but more long-term limb toxicity (fibrosis, edema, joint dysfunction) due to larger field and higher dose.
Conclusions
Preoperative RT results in significantly more wound complications than postoperative RT. However, late toxicity is greater with post-op RT (larger field, higher dose), and the OS signal favors pre-op RT. The choice of timing should individualize based on tumor location, size, expected wound healing, and patient functional goals.
Key Limitations
Key Limitations: Trial stopped early after interim analysis for wound complication difference; only powered for wound complications, not OS or LC; imbalance in lower extremity tumors (higher wound risk) in pre-op arm; 3.3-year median follow-up limited for long-term functional outcomes; modern negative pressure wound therapy not available.
Clinical Context
This is the definitive trial comparing pre-op vs. post-op RT timing in extremity STS. Current practice leans toward pre-op RT (50 Gy) because: smaller field, lower dose, better functional preservation long-term, and potential biology benefit (downstaging, improved resectability). Wound complications with pre-op RT (especially lower extremity) require surgeon-RT team communication and may warrant reconstructive planning.
References