Surgically Managed Gastrointestinal Stromal Tumors: A Comparative and Prognostic Analysis

Abstract

Tyrosine kinase inhibitors have been shown to have marked clinical efficacy in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). We performed a comparative and prognostic analysis of our experience with surgically managed GIST to determine factors associated with adverse oncologic outcomes. Oncologic outcomes of 191 patients with primary GIST surgically managed between 1978 and 2004 at a single institution were reviewed. Prognostic factors were analyzed by Cox analysis (hazard ratio [HR] and 95% confidence interval [95% CI]) and included age, sex, disease presentation (asymptomatic vs. symptomatic), tumor site (stomach, small bowel, colorectal), disease extent (localized vs. metastatic) and risk levels (high, intermediate, low, very-low) assigned on the basis of size and number of mitoses according to current National Institutes of Health recommendations. Primary end points were disease-free survival (DFS) and disease-specific survival (DSS). A total of 186 patients (97%) had c-kit-positive GIST. There were 54% high, 22% intermediate, 18% low, and 8% very low risk GIST originating from the stomach (54%), small bowel (36%), and colon and rectum (10%). Median patient age was 65 (range, 13-91) years, and 108 subjects (57%) were male. Seventy-two percent of patients had symptomatic local disease, and 21% patients had synchronous metastases. Most (95%) underwent R0 resections of their primary tumor. Among 146 patients (76%) with localized disease at presentation undergoing R0 resection, the 5-year DFS was 65%. High-risk GIST (HR 12, 95% CI, 5-32, P < .0001), symptomatic presentation (HR 2.5, 95% CI, 1.1-6, P = .04), and GIST in the small bowel (HR 2.8, 95% CI, 1-5, P = .003) were independently associated with decreased DFS. After a median follow-up of 63 months among survivors, the 5-year DSS was 68%. High-risk disease (HR 14.3, 95% CI, 5-41, P < .0001), symptomatic presentation (HR 3.1, 95% CI, 1.2-7.9, P = .02), and GIST in the small bowel (2.6,3 95% CI, 1-5, P = .006) were independently associated with decreased DSS. High-risk GIST are associated with increased disease recurrence and decreased survival despite complete surgical resection. These patients should receive adjuvant therapy in the form of tyrosine kinase inhibitors.