Some tumors can be removed by surgery and pose little risk of coming back. This type of tumor is often referred to as a benign tumor. However, other tumors may have a higher risk of coming back. These tumors are commonly called malignant tumors. If a tumor returns after surgery, it is called a recurrence.
Most cancers arise from a single tumor at a single site in the body. This tumor is called a primary tumor. After surgery, a tumor can return at the same site (a local recurrence) or a new tumor can occur at a different site (metastasis). Metastases (commonly called “mets”) can be present at the time of diagnosis or they can appear sometime after surgery (a recurrence). They form when tumor cells detach from the primary tumor and travel through the circulatory system (blood, lymph) and attach in distant locations. These tumor cells then act as seeds for new tumors.
Gastrointestinal stromal tumors (GISTs), unlike other cancerous tumors, are not classified as benign or malignant. Rather, they are stratified on a risk scale of low to high risk based on tumor size, mitotic index and location of tumor. Mutation may also play a role in determining risk. The NCCN guidelines strongly recommend testing of tissue removed by biopsy or surgery for mutations in the KIT and PDGFRA genes or the SDH gene if no mutations were found in the KIT or PDGFRA. For more information on GIST Mutations and Mutation Testing.
Based on a consensus guideline formulated in 2001 on the diagnosis and morphologic prognostication of GISTs, many experts consider that all GISTs may have malignant potential (Zhao & Yue, 2012). Other experts consider gastric GISTs smaller than 2cm essentially benign, whereas the non-gastric ones tend to be have a higher risk of recurrence and malignant potential (NCCN guidelines, 2016).
There is a perception that all GISTs have a high chance of a recurrence after surgery. This is not the case. In fact, in a large phase III trial (ACOSOG Z9001) for preventative Gleevec, about 45% of the patients entering the trial had a low risk of recurrence (Blackstein, et.al, 2010). The chart below, from a different group of patients (n=259) from a study of GIST patients in western Sweden, shows a similar pattern, with 45.2% of these patients either low or very low risk of recurrence. It gives a rough idea of how many GIST patients fit into each risk category. Other series of patients might have somewhat different ratios.
Knowing your risk of recurrence is especially important if you are considering adjuvant Gleevec (imatinib). Patients with a low risk or very low risk tumor may not need to take adjuvant Gleevec (imatinib). At least three years of adjuvant treatment is recommended for GIST patients with a high risk of recurrence. In the United States adjuvant Gleevec (imatinib) is also recommended for patients with intermediate risk, although the duration of treatment is not specified (NCCN, 2016). A recent study by Quek, et.al, 2016 has shed a light on this uncertainty by demonstrating how mutational analysis can improve risk stratification for this subgroup of patients who may benefit from adjuvant Gleevec (imatinib). In the study, intermediate risk GIST patients with KIT Exon 11 deletion mutations had inferior clinical outcomes, with recurrence-free survival comparable to high risk patients.
There are several different methods used to classify the risk of recurrence in GIST. Some have advantages over others for specific cases (for example, if the primary tumor site is unknown, one method has advantages over others). An understanding of how it is calculated should prove helpful in determining your prognosis and treatment plans with the help of your health care team.
Blackstein, M., Corless, C., Ballman, K., Antonescu, C., Blanke, C, Demetri, G.,…DeMatteo, R. American College of Surgeons Oncology Group (ACOSOG) Intergroup. (2010). Risk assessment for tumor recurrence after surgical resection of localized primary gastrointestinal stromal tumor (GIST): North American Intergroup phase III trial ACOSOG Z9001. GI ASCO. [Abstract].
National Comprehensive Cancer Network (2016). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines, Version 1.2017. Soft Tissue Sarcoma).
Nilsson, B., Bümming, P., Meis-Kindblom, J. M., Odén, A., Dortok, A., Gustavsson, B., Sablinska, K. and Kindblom, L.-G. (2005). Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer, 103: 821–829. doi:10.1002/cncr.20862.
Quek, R., Farid, M., Kanjanapan, Y., Lim, C., Tan, I. B., Kesavan, S., Lim, T. K. H., Oon, L. L.-E., Goh, B. K., Chan, W. H., Teo, M., Chung, A. Y., Ong, H. S., Wong, W. K., Tan, P. and Yip, D. (2016), Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor. Asia-Pac J Clin Oncol. doi:10.1111/ajco.12603.
Zhao & Yue. (2012). Gastrointestinal stromal tumor. J Gastrointest Oncol. 2012 Sep; 3(3): 189–208. doi: 10.3978/j.issn.2078-6891.2012.031.