Background: Recent breakthroughs regarding the oncogenesis of gastrointestinal stromal tumors (GISTs) have led to the wider use of imatinib mesylate in the treatment of advanced GISTs. However, the role of imatinib in an adjuvant setting has yet to be established, mainly owing to the lack of an accurate system to prognosticate recurrences and/or metastases. The aims of this study were to identify factors prognostic for an unfavorable postoperative outcome, and to enhance the current NIH-consensus risk-group stratification system (Fletcher's system).
Methods: A retrospective review was conducted in 303 consecutive patients who had undergone surgical resection of primary GISTs during the study period (1987-2003). In addition to Fletcher's system, which is based on morphologic variables (tumor size and mitotic count), with four risk groups: very low risk, low risk, intermediate risk, and high risk, the predictive potential of any major preoperative, intraoperative, or postoperative clinical factor was statistically evaluated.
Results: In addition to tumor size and mitosis, four operative variables were found to affect disease-free survival: peritoneal dissemination, metastasis, invasion, and tumor rupture. Patients presenting with at least one of these "clinically malignant factors" had an unfavorable outcome (i.e., they were potential candidates for adjuvant therapy). We therefore modified Fletcher's system by adding a new patient group, termed the "clinically malignant group," (patients having at least one of the "clinically malignant factors"). With this modification, the outcomes of patients in the "new" very-low-risk and low-risk groups remained favorable, but the outcomes of patients in the "clinically malignant group" and the "new" high-risk group bceame unfavorable.
Conclusion: This modified Fletcher's system, enhanced by the addition of "clinically malignant factors," can distinguish patients with a possible unfavorable outcome from those who require no therapy other than surgery. Patients in the "clinically malignant group" could be potential candidates for adjuvant therapy using imatinib.