There is no screening for GIST, so finding a very small, localized primary tumor tends to happen most with gastric GIST, during an endoscopy that is performed for other reasons. A 2-cm submucosal gastric mass found on endoscopy should be biopsied to determine whether it is benign, such as leiomyoma, or malignant, such as lymphoma, GIST, or other rare entities.

For GIST less than 2 cm, preemptive removal is advisable in high-risk cases, while serial endoscopies on a regular basis could be considered in some scenarios. However, immediate removal via laparoscopic surgery would generally be preferred, especially in younger patients, to eliminate the need for lifelong endoscopic surveillance.

Localized GIST greater than 3 cm warrant surgical removal owing to the higher risk of recurrence. A caveat to that is that the surgical morbidity must be considered. For a GIST that is very close to the gastroesophageal junction, resection might lead to severe gastroesophageal reflux. Likewise, for a tumor in the rectum, the risk of the surgery resulting in the lifelong need for a colostomy bag has to be considered. In some cases, neoadjuvant imatinib can achieve cytoreduction, which would alter the surgical approach and/or avoid these complications, but, in other situations, keeping the patient on medical therapy indefinitely is preferable for its lower morbidity compared with a more extensive or debilitating surgery that would result in lifelong side effects.

Thus far, molecular profiling to predict outcomes in GIST has not been as powerful as the established GIST risk stratification algorithms based on factors such as size and mitotic count; nevertheless, it remains true that the 3 most important clinical considerations in treating GIST are “mutation, mutation, mutation.” Mutational analysis is required to inform decision making regarding adjuvant therapy. Any patient with a greater than 10% or 15% chance of recurrence should be advised of the risks and benefits of adjuvant therapy vs surveillance, and imatinib would be inappropriate for less-sensitive or less-resistant genotypes such as PDGFRA D842V or some KIT exon 17 primary mutations. Further, 70% of cases of succinate dehydrogenase deficiency are due to a germline mutation, and genetic counseling and family screening may be beneficial, as these patients may also be at risk for other cancers such as paraganglioma, pheochromocytoma, or renal cell carcinoma. Thus, lifelong surveillance is indicated.