Natural History and Prognosis of Localized Gastrointestinal Stromal Tumors in the Pre- and Post-imatinib Eras

Abstract

Gastrointestinal stromal tumors (GISTs), historically misclassified as leiomyomas, leiomyosarcomas, or schwannomas, are the most common mesenchymal neoplasms found in the gastrointestinal (GI) tract. The cornerstone in the treatment of GISTs has always been surgical resection, yet historically this has been associated with suboptimal overall survival and recurrence rates [1, 2]. However, there was a major breakthrough in 1998 when it was discovered that GISTs arise from the interstitial cell of Cajal and are molecularly characterized principally by mutations in the c-KIT and PDGFRA genes [3]. Since then, multiple clinical trials have evaluated the efficacy of imatinib mesylate, an oral tyrosine kinase inhibitor (TKI), as a treatment modality for GIST with excellent results [2, 4–7]. Today, imatinib plays a critical role in both the neoadjuvant and adjuvant treatment of GISTs, and in addition to other TKIs such as sunitinib and regorafenib, these drugs have fundamentally altered the natural history of both localized and metastatic GIST. Given that TKI therapy is costly and is associated with long-term adverse effects, it is critical to understand the natural history of localized GISTs as well as the prognostic factors for recurrence in order to identify those patients who would benefit most from TKI therapy. In this chapter, we review the natural history and prognosis of localized GISTs before the introduction of imatinib, the landmark trials demonstrating its efficacy, and the improved prognosis of localized GISTs after the introduction of imatinib.