GIST cannot be reliably categorized as benign or malignant based on H&E staining, and, in general, the morphology of GIST is much less telling than for common cancers such as breast and colon cancers. GIST that appear malignant microscopically may never return, and tumors that appear benign may ultimately prove fatal. Consequently, GIST are risk stratified using a number of different models. I use the tool developed by Joensuu et al that incorporates the primary tumor size, mitotic count, tumor rupture, and tumor site. One of the advantages of this tool is that the mitotic rate is treated as a continuous variable (eg, mitotic rates of 6 and 26 are treated differently even though they are both >5). Generally, high-risk primary tumors are associated with size greater than 10 cm with any mitotic rate, a high mitotic rate (>5 mitoses/50 HPF), and/or rupture. Rupture is associated with a very high risk of recurrence that is more than 90% independent of other factors. Gastric GIST are associated with a lower risk of recurrence, regardless of size, than GIST in the small intestine, colon, or rectum.

Esophagogastroduodenoscopy and endoscopic ultrasound with the possibility of fine needle aspiration allows gastroenterologists to identify GIST much earlier than in the past. Many gastric GIST are discovered incidentally while a patient is being evaluated for Helicobacter pylori, reflux, or gastritis. For very small resected GIST (eg, <1 cm) determined to pose no risk of recurrence or spread, follow-up generally is not necessary. For larger resected GIST, say 3 to 4 cm, even with low risk of recurrence, a reasonable approach might be abdominal and pelvic computed tomography every 6 months for 3 years and then annually for a few additional years. One of the reasons for monitoring for recurrence even in the setting of low-risk GIST is that, if such tumors do recur, highly effective medical therapies may be offered. You do not want to let a patient recur and become symptomatic.

One area of uncertainty centers on the impact of adjuvant therapy on GIST and the optimal duration of systemic therapy for an individual’s risk status. The fundamental question, which future clinical trials may answer, is whether adjuvant imatinib therapy kills residual GIST cells or if it merely puts them in a state of quiescence from which they can recover. The PERSIST-5 study was a 5-year trial designed to assess the impact of a longer duration of adjuvant therapy to prevent recurrence in patients with resected KIT exon 11–mutant GIST. It included adults at intermediate or high risk of recurrence, and one of the interesting findings was that, as long as these patients remained on imatinib for the entire 5 years, there were no recurrences. For those who did recur, the recurrence was within 2 years of the discontinuation of imatinib. Thus, we must get to the bottom of that phenomenon to understand whether indefinite therapy with imatinib may be warranted and for whom (ie, at what level of risk for GIST recurrence).