Limb-sparing surgery plus radiotherapy results in superior survival: an analysis of patients with high-grade, extremity soft-tissue sarcoma from the NCDB and SEER

Small randomized trials have not shown an overall survival (OS) difference among local treatment modalities for patients with extremity soft-tissue sarcomas (E-STS) but were underpowered for OS. We examine the impact of local treatment modalities on OS and sarcoma mortality (SM) using two national registries. The National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed separately to identify patients with stage II-III, high- grade E-STS diagnosed between 2004 and 2013 and treated with (1) amputation alone, (2) limb-sparing surgery (LSS) alone, (3) preoperative radiation therapy (RT) and LSS, or (4) LSS and postoperative RT. Multivariable analyses (MVAs) and 1:1 matched pair analyses (MPAs) examined treatment impacts on OS (both databases) and SM (SEER only). From the NCDB and SEER, 7828 and 2937 patients were included. On MVAs, amputation was associated with inferior OS and SM. Relative to LSS alone, both preoperative RT and LSS (HR, 0.70; 95% CI: 0.62-0.78) and LSS and postoperative RT (HR, 0.69; 95% CI: 0.63-0.75) improved OS in NCDB analyses with confirmation by SEER. Estimated median survivals from MPA utilizing NCDB data were 7.2 years with LSS alone (95% CI: 6.5-8.9 years) vs 9.8 years (95% CI: 9.0-11.2 years) with LSS and postoperative RT. A MPA comparing preoperative RT and LSS to LSS alone found median survivals of 8.9 years (95% CI: 7.9-not estimable) and 6.6 years (95% CI: 5.4-7.8 years). Optimal high-grade E-STS management includes LSS with preoperative or postoperative RT as evidenced by superior OS and SM.