Panel deliberation.
Pretreatment re-excision is indicated when initial excisional biopsy or resection leaves behind gross residual tumor, has microscopically involved margins, or when the margin status is uncertain28-30. In such situations, pretreatment re-excision is considered only when a wide re-excision can be achieved with the aim of resecting all residual tumor with negative margins, without causing significant surgical complications and undue delay in starting chemotherapy. Pretreatment re-excision in RMS, particularly for trunk and extremities30, plays a critical role in ensuring margin-negative resection, downgrading risk stratification, and de-intensification of therapy. Patients who achieve a negative resection margin before starting chemotherapy with pretreatment re-excision are classified as group 1, have improved survival, and potentially qualify for reduced radiation dose31. All outcome analyses are improved for group 1 in comparison to group 2 and group 3. Group 1 achieved by either upfront resection or pretreatment re-excision have equally good outcomes28-30. In patients with group 1 disease, FOXO fusion-negative status may avoid the need for radiation therapy32.
The panel suggests early preoperative radiation therapy for patients with unresectable RMS. (Weak recommendation, Certainty of evidence: Very Low, Supplemental Table S6)
We identified one retrospective cohort study enrolling 88 patients assessing preoperative radiation therapy for unresectable tumors versus no preoperative radiation therapy. The certainty of evidence is very low. Pooled results did not indicate any significant difference in overall mortality, mortality/event, or relapse. Incomplete resection was significantly lower in patients undergoing preoperative RT versus no preoperative RT (OR 0.02, 95% CI 0.00 to 0.08).