Association of Definitive Local Therapy with Survival in Patients with Metastatic Soft Tissue Sarcoma

Abstract

Definitive local therapy is often used in patients with metastatic soft tissue sarcomas (STS) to reduce morbidity associated with local tumor progression. However, the potential survival benefit of this therapeutic approach has not been rigorously investigated. We hypothesized that definitive local therapy is associated with improved overall survival (OS) in patients with metastatic STS. Patients aged ≥18 years with newly diagnosed metastatic STS treated with chemotherapy from 2004-2015 were identified from the National Cancer Database. Patients were dichotomized into the following cohorts: definitive local therapy (defined as either definitive dose radiotherapy (RT), definitive surgery, or surgery with perioperative RT) or conservative therapy (defined as systemic therapy alone). The association between definitive local therapy and OS was assessed using Cox proportional hazards models. Factors associated with the receipt of definitive local therapy were identified with multivariable logistic regression. A total of 4,180 patients were identified of whom 1,714 (41%) were treated with definitive local therapy and 2,466 (59%) with conservative therapy. Of those treated with definitive local therapy, 58% were treated with surgery alone, 22% with definitive dose RT alone, and 20% with surgery and perioperative RT. Compared with conservative therapy, receipt of any definitive local therapy was associated with improved OS with a median survival of 17.9 vs. 10.1 months and a 5-year OS rate of 15.8% vs 6.4% (P < 0.001). These findings remained after landmark analyses of patients who survived at least 24 months (P < 0.001), suggesting they were unaffected by immortal time biases. The survival benefit of local therapy remained on multivariate analyses with a stepwise improvement with surgery and combined modality local therapy, specifically RT (HR: 0.78; 95% CI, 0.68-0.88; P <0.001), surgery (HR: 0.66; 95% CI, 0.60-0.72; P < 0.001), and combined surgery and RT (HR: 0.42; 95% CI, 0.36-0.48; P < 0.001). On multivariate analysis, treatment at an academic institution (OR: 1.17, 95% CI 1.00-1.37, P = 0.05) was associated with receipt of local therapy, whereas lack of health insurance (OR: 0.66, 95% CI 0.49-0.88, P < 0.01) and Medicare insurance (OR: 0.78, 95% CI 0.64-0.95, P < 0.05) were associated with omission of local therapy. Analysis of a large national cancer registry of patients with metastatic STS suggests that chemotherapy plus aggressive local therapy is associated with a significant survival benefit compared to standard chemotherapy alone. Further investigation and prospective trials to better define the patient population that benefits from aggressive local therapy in this clinical situation is warranted.