Radiation and Chemotherapy Improve Survival in Patients with High-Risk Soft Tissue Sarcomas of the Extremities: An Updated Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database

Abstract

The primary treatment modality for non-metastatic soft tissue sarcomas (STS) of the extremity is surgical resection. This can be accomplished with amputation, or limb sparing surgery (LSS) when feasible. Radiation therapy improved survival in patients with tumors that were high grade or undifferentiated and >5cm (high risk) in a prior SEER analysis. The role of chemotherapy remains controversial in STS. The SEER 18 registries database was queried to identify patients age 18 and older with pathologically confirmed STS of the extremity diagnosed in 2004 or later that underwent surgical resection. Patients with Kaposi’s sarcoma were excluded as well as those with metastatic disease, <3 months of follow up and if the type of surgery was not specified. The primary endpoint of this study was overall survival, which was determined using the Kaplan and Meier method. Survival curves were subsequently compared using log rank analysis. A total of 8,584 patients were identified that met inclusion criteria, Females comprised 3,862 patients and males 4,722 patients. The average age at diagnosis was 57 (range 18-98). Grade III or undifferentiated tumors were present in 3,860 patients while 4,915 patients had tumors >5cm. The 5 year OS for patients who underwent amputation was 53.4% compared to 77.0% with LSS, corresponding to a HR of 0.40 (p<0.001). Median OS was 68 months with amputation and not reached at 10 years with LSS. Of the 8,122 patients who underwent LSS, 4,369 patients were known to have received radiation therapy and 1,135 were known to have been treated with chemotherapy. Neither radiation therapy nor chemotherapy improved survival in the entire cohort of patients undergoing LSS. In a subset of 2,331 patients with high risk tumors, radiation improved 5 year OS from 51.1% to 59.6% while median OS improved from 71 to 97 months, corresponding to a HR of 0.78 (p=0.002). In the same subset of patients treated with radiation, 689 (37.2%) had neoadjuvant radiation with or without postoperative radiation (PORT) and 1,161 (62.8%) had PORT alone. 5 year OS was 58.5% with PORT and 61.5% with neoadjuvant radiation while median OS was 89 and 97 months respectively, corresponding to a HR of 0.97 (p=.671). For the 720 patients with high risk tumors who were known to have received chemotherapy, the 5 year OS and median OS were 61.7% and 117 months respectively versus 58.5% and 83 months respectively for patients not known to receive chemotherapy, corresponding to a HR of 0.83 (p=0.025). The findings of this analysis support continued use of LSS in surgically eligible patients with STS of the extremity. While neither radiation therapy nor chemotherapy improved survival in all comers treated with LSS, the subset of patients with high risk tumors (high grade/ undifferentiated and >5cm) showed a significant survival benefit from both modalities in addition to surgery. The timing of radiation therapy, neoadjuvant versus PORT did not impact survival in this subset of patients.