Surgical Margin and Risk of Local Recurrence in Children and Young Adults With Nonrhabdomyosarcoma Soft Tissue Sarcoma

Importance: The extent of negative margin necessary to achieve a high rate of local tumor control in children and young adult patients with nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) is unknown. Objective: To evaluate the impact of negative margin extent on local tumor control in children and young adult patients with NRSTS undergoing R0 resection as part of risk-adapted multimodality treatment. Design, Setting, and Participants: This multicenter prospective clinical trial was conducted at Children's Oncology Group (COG) member sites from February 2007 through February 2012. Analysis was performed on the final dataset June 30, 2018, with a median follow-up of 6.2 years. Reviewers of margin status/extent were blinded to local control outcomes. Patients included 266 eligible/evaluable individuals younger than 30 years with nonmetastatic NRSTS who were enrolled in the COG ARST0332 trial and underwent upfront or delayed R0 resection as part of treatment. Patients who underwent an amputation or did not receive protocol-specified radiotherapy were excluded. These data were analyzed from January 2023 through July 2026. Intervention: Risk-adapted treatment included 3 patient groups with upfront or delayed surgery with or without radiation therapy with or without ifosfamide/doxorubicin chemotherapy, based on the extent of initial resection, surgical margin status, tumor size, and histologic grade. Main Outcomes: Cumulative incidence of local recurrence based on treatment approach and surgical margin extent and outcomes after local recurrence. Results: Of 266 patients (median age 13.7 [range, 2.1-27.6] years; 138 female [52%] and 128 male [48%]) who underwent upfront (n = 207) or delayed (n = 59) R0 resection, 132 had measured surgical margins: 1 mm (n = 56), 2 to 5 mm (n = 50), or 6-mm or larger (n = 26). The 5-year cumulative incidence of local recurrence overall was 4.4%. Local recurrence occurred in 10 of 178 patients treated with surgery alone (5.6%) and 2 of 88 patients treated with surgery and chemoradiotherapy (2.3%). Among the 132 patients with measured surgical margins, the 5-year cumulative incidence of local recurrence was 4.9% for 1-mm margins, 2.0% for 2- to 5-mm margins, and 0% for 6-mm or larger margins. Local recurrence occurred in 10 of 178 (5.6%) patients with tumors smaller than 5 cm treated with margin-negative surgery alone, 1 of 29 (3.4%) patients with tumors larger than 5 cm treated with margin-negative surgery followed by chemoradiotherapy, and 1 of 59 (1.7%) patients with initially unresectable disease treated with neoadjuvant chemoradiotherapy. Five of 12 patients with local recurrence were alive without further disease progression. Conclusions and Relevance: In this study, the local recurrence rate after R0 resection among children and young adult patients treated with risk-based therapy for nonmetastatic NRSTS was low, and some patients underwent successful salvage therapy with durable long-term disease control. Wider (>1 mm) negative margins further decrease local recurrence risk. Close surgical margins may be adequate in some clinical settings, particularly in the context of chemoradiotherapy, according to a risk-adapted approach. Trial Registration: ClinicalTrials.gov Identifier: NCT00346164.