Lymph node metastasis in high-risk soft tissue sarcoma: Predictors and survival in a population-based SEER study

Soft tissue sarcoma comprises heterogeneous malignant mesenchymal tumours with variable metastatic behaviour. Although spread is usually haematogenous, epithelioid sarcoma, rhabdomyosarcoma, clear cell sarcoma, and angiosarcoma have recognised nodal metastatic potential. Population-level data on nodal metastasis in these high-nodal-risk subtypes remain limited.

This retrospective population-based cohort study used prospectively collected SEER-17 registry data. Adults aged ≥18 years with microscopically confirmed epithelioid sarcoma, rhabdomyosarcoma, clear cell sarcoma of soft tissue, or angiosarcoma/haemangiosarcoma diagnosed between 2000 and 2022 were included. Nodal positivity was defined as AJCC N1 versus N0 disease. Overall survival was measured from diagnosis to death from any cause or last follow-up, and cancer-specific survival from diagnosis to sarcoma-related death. Logistic regression identified predictors of nodal positivity. Cox models assessed survival associations, and Fine-Gray competing-risks analysis evaluated cancer-specific mortality with non-cancer death as a competing event.

Of 12,154 identified patients, 9682 formed the final analytical cohort. Cox modelling included 8909 patients, while logistic regression was restricted to 1348 with documented N0/N1 status. Among staged patients, 236 had nodal metastasis, giving a nodal positivity rate of 17.5%. Rates were highest in rhabdomyosarcoma and clear cell sarcoma, at 26.1% and 25.8%, respectively, followed by epithelioid sarcoma at 15.2% and angiosarcoma at 12.6%. Distant metastasis was the strongest independent predictor of nodal positivity (OR 3.84, 95% CI 2.05-7.21), while head and neck primary site was also associated with increased odds versus extremity tumours (OR 4.00, 95% CI 1.77-9.23). N1 status independently predicted worse overall survival (HR 1.40), cancer-specific survival (HR 1.50), and cancer-specific mortality (SHR 1.54).

Nodal metastasis occurs at clinically meaningful rates in high-nodal-risk soft tissue sarcomas and is independently associated with adverse survival outcomes.