Stage IV gastrointestinal stromal tumors: Epidemiology, treatment and outcomes in adult US patients

462 Background: To evaluate epidemiology, treatment and outcomes of stage 4 gastrointestinal stromal tumors (GIST). Methods: The 2010-2016 United States National Cancer Database was queried for adult patients diagnosed with invasive GIST (ICD code 8936) at AJCC stage 4, without prior malignant disease. Overall survival (OS) was evaluated using Cox proportional hazards regression, accounting for potential confounders in multivariable models. Results: A total of 1,578 stage 4 GIST were included (13.3% of all GIST) with a male:female ratio of 1.38:1. The most common cancer site was the stomach (55.4%) and small intestine (40% of stage 4 GIST). At diagnosis, median age was 62 years and median tumor diameter 10 cm. Distant organ metastases were reported in 58.7%, the most frequent being hepatic (n = 801, 50.8% of stage 4 GIST). The majority of stage 4 GIST patients received systemic therapy (78.6%), either alone (35.4%) or combined surgery+systemic therapy (43.3%). Systemic therapy was administered neoadjuvant in 6.9%, adjuvant in 32%, and neoadjuvant+adjuvant in 5.1% of surgically resected patients. Another n = 204 patients (12.9% of all stage 4 GIST) were treated with surgical resection alone. GIST overall survival rates were 88%, 77%, 67% and 51% at 1, 2, 3, and 5 years, respectively. On multivariable Cox proportional hazard models, primary GIST treatment independently affected OS: compared to combined surgery+systemic therapy, OS was shorter for patients receiving systemic therapy alone (HR = 2.77 (95% CI: 2.12-3.61, p < 0.001)) and no treatment (HR = 4.2 (95% CI: 2.75-6.43, p < 0.001)). No significant OS difference was evident comparing surgery+systemic therapy and surgery alone (HR = 1.23 (95% CI: 0.88-1.72, p = 0.227)). In subgroup analyses of patients undergoing surgical resection, no statistically significant OS difference was evident comparing neoadjuvant, adjuvant and combined neoadjuvant+adjuvant systemic therapy on multivariable analyses. Treatment at non-academic vs. academic centers was associated with shorter OS (multivariable HR = 1.36 (95% CI: 1.1-1.69, p = 0.005)). Further independent OS predictors were male sex (vs. female HR = 1.28 (95% CI: 1.03-1.59, p = 0.023)), older age, higher comorbidities, higher cancer grade, and larger cancer diameter. Conclusions: Stage 4 GIST is a rare gastrointestinal malignancy that most commonly manifests in the stomach and small intestine in male patients, with frequent hepatic metastases and excellent 5-year OS rates of up to 51%. Combined surgery+systemic therapy demonstrates best outcomes, although surgical resection alone might yield comparable results in selected patients.