Regional lymph node involvement varies by histologic subtype in extremity soft-tissue sarcoma

Abstract Purpose Regional lymph node involvement in extremity soft-tissue sarcoma (STS) is uncommon, but its frequency varies by histologic subtype. We evaluated contemporary histology-specific nodal involvement and cancer-specific survival (CSS). Methods We analyzed malignant extremity STS diagnosed in SEER during 2018–2023 using an audited, reproducible ICD-O-3 morphology code set. Multivariable logistic regression assessed node-positive disease. Two Cox models and a Fine-Gray competing-risk analysis evaluated CSS. Adult-only and nonmetastatic-only sensitivity analyses tested the histology findings. Results Among 9,311 eligible cases, 8,636 had known nodal status; 376 (4.4%) were node-positive. Nodal positivity was highest in rhabdomyosarcoma (30.9%), clear cell sarcoma (29.0%), epithelioid sarcoma (20.8%), and angiosarcoma (13.7%). Adjusted odds were highest for clear cell sarcoma (OR 17.72), rhabdomyosarcoma (OR 7.47), and epithelioid sarcoma (OR 6.82). Synovial sarcoma was not statistically associated with higher odds relative to liposarcoma (OR 1.15; 95% CI 0.60–2.20). Node-positive disease was associated with worse CSS in the tumor-adjusted Cox model (HR 1.46; 95% CI 1.22–1.73) and after additional treatment adjustment (HR 1.35; 95% CI 1.13–1.60). Conclusions Recorded regional nodal involvement varied substantially by histologic subtype and was associated with worse CSS. The adult-only, nonmetastatic-only, and competing-risk analyses were consistent with the primary findings. These observational data support further evaluation of histology-informed nodal assessment but do not establish that a specific nodal staging strategy improves outcomes.