Purpose/Objective(s): The role of systemic therapy in the definitive management of non-metastatic adult soft tissue sarcoma is evolving. We sought to retrospectively analyze factors associated with overall survival (OS) within a cohort of chemotherapy-sensitive adult soft tissue sarcoma histologies using the National Cancer Database (NCDB).

Materials/Methods: The NCDB was queried from 2004-2012 for adult patients with chemotherapy-sensitive non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) histologies, including undifferentiated soft tissue sarcoma, synovial sarcoma, angiosarcoma, fibrosarcoma, mesenchymal extraskeletal chondrosarcoma, leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma, and embryonal sarcoma of the liver. Histologies were chosen based on reported chemotherapy response rates. Exclusions included primary sites in bone, joint, skin, retroperitoneum, heart, or unknown location; clinical stage IV or unknown clinical stage; grade 1; no definitive surgery performed; unknown sequencing of chemotherapy and surgery; unknown receipt of chemotherapy; intraoperative chemotherapy; unknown sequencing of radiotherapy and surgery; or date of last follow-up <3 months from diagnosis. Univariate and multivariate Cox proportional hazards modeling were used to analyze variables that were related to OS.

Results: Identified were 10,359 patients meeting inclusion criteria. Of these, 8,538 (82.4%) received no chemotherapy. Radiotherapy was given in 5,689 (54.9%) patients. On multivariate analysis, adjuvant chemotherapy (HR 1.19, p = 0.02), increasing age (HR 1.39, p < 0.01 for age 45 – 65; HR 2.69, p < 0.01 for age >65), Charlson-Deyo Comorbidity Score (HR 1.23, p < 0.01 for score of 1; HR 1.62, p <0.01 for score ≥ 2), tumor size (HR 1.34, p = 0.01 for >2 – 5 cm; HR 2.06, p < 0.01 for >5 – 10 cm; HR 3.22, p < 0.01 for >10 – 15 cm; HR 3.72, p < 0.01 for >15 cm), grade (HR 1.80, p < 0.01 for poorly differentiated; HR 1.85, p <0.01 for undifferentiated), positive margins (HR 1.53, p < 0.01 for R1; HR 2.59, p <0.01 for R2; HR 1.58, p < 0.01 for positive margin not otherwise specified), clinical stage III (HR 1.18, p = 0.02), and angiosarcoma histology (HR 1.81, p < 0.01) were associated with worse OS. Improved OS was associated with neoadjuvant chemotherapy (HR 0.84, p = 0.04), female gender (HR 0.84, p < 0.01), radiotherapy (HR 0.78, p < 0.01 for preoperative; HR 0.68, p < 0.01 for postoperative; HR 0.66, p = 0.02 for pre- and postoperative), liposarcoma histology (HR 0.58, p < 0.01) and undifferentiated pleomorphic sarcoma histology (HR 0.85, p = 0.01).

Conclusion: Prognostic factors for adult non-metastatic, chemotherapy-sensitive NRSTS were identified from a large modern patient cohort within the NCDB. Both neoadjuvant chemotherapy and radiotherapy, given pre- and/or postoperatively, were associated with a significant OS benefit.