Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.
Several factors influence the prognosis of gastrointestinal stromal tumors (GISTs), but the primary prognostic factors include the tumor staging and the tumor resectability.
The staging for GISTs ranges from Stage I through Stage IV and generally follows the American Joint Committee on Cancer’s TNM system. T stands for tumor size. N indicates spread to nearby lymph nodes, which is rare with GISTs. Lastly, M stands for metastasis to other regions of the body from the primary tumor site. The most frequent sites of metastasis for GISTs include the liver, bones, lungs, and intraperitoneal tissues.1 The final key piece of information to categorize a tumor into a stage is the mitotic rate, or how rapidly the tumor cells are growing and dividing. A slower mitotic rate predicts a better prognosis.1 Mitotic rates are determined through lab testing of the tumor tissue after a biopsy has been performed.
In the case of GIST, there are 2 different stage grouping schemes which are location-dependent. The first stage grouping scheme is for tumors located in the stomach or the omentum. The second grouping scheme is for tumors located in the small intestine, esophagus, colon, rectum, or peritoneum. GISTs starting in the stomach or omentum are unlikely to grow rapidly or metastasize compared with GISTs originating in other locations.1
Another method of staging GIST utilizes the SEER database, which differs from the American Joint Committee on Cancer’s TNM staging by grouping cancers into localized, regional, and distant stages.2
GIST tumors that can be resected or removed without causing major health problems are deemed resectable. Tumors that are deemed unresectable have either metastasized to other regions or are in a location where it is too risky to operate. There are some cases when a surgeon may classify a tumor as borderline or marginally resectable if it is unclear whether the tumor can be removed in its entirety.1 Situations where GISTs are completely resectable have a better prognosis than situations where the tumors are unresectable. In one study, overall survival of patients with complete resection of a GIST survived a median of 52 months compared with the median 12-month survival rate of those whose GIST could not be fully resected.3
Certain factors make GISTs more likely to recur or grow back, including tumor size, the mitotic index, and the tumor location.4 The larger the primary tumor is, the more likely it is to recur. The mitotic index indicates how many cells are actively replicating, so the higher the number, the more likely the GIST will recur. The tumor location also plays a role in whether the GIST may recur. GISTs found in the stomach have a lower likelihood of recurrence than other locations of origin. Risk of GIST recurrence is categorized as low, intermediate, or high by considering these 3 factors.
GIST Growth and Metastasis Prediction Tools
Doctors can reach reasonable conclusions to predict GIST prognosis based on the location of the tumor, the size of the tumor, the mitotic rate, and whether the tumor has ruptured or not.1 Prediction tools such as KIT and PDGFRA genotyping and evaluation of the presence of specific circulating biomarkers for GIST may help determine which GISTs are potentially more dangerous than others in terms of rapid growth and metastasis. Physicians and researchers are investigating how well GIST responds to treatment with specific cancer drugs and how the response correlates to the genotype of specific mutations in the KIT or PDGFRA genes which promote GIST growth.1 Ongoing investigations are studying the usefulness of molecular circulating biomarkers such as KIT, PDGFRA, BRAF, SDH, SETD2, and ROR2 DNA and microRNAs (miRNAs) for potential GIST surveillance and prognosis.5
Aggressive GIST Behavior
GISTs exhibit a variety of growth behaviors from slow-growing benign tumors to aggressive cancerous tumors which metastasize to other regions of the body. Histologic analyses of GIST tumor biopsies help to predict prognosis. The most aggressive GISTs demonstrate the following behaviors:6
- GIST tumor size of larger than 5 centimeters (cm) indicates moderate malignancy potential, and tumor size larger than 10 cm indicates high malignancy potential.
- Tumors located in the small intestine or other locations are generally more aggressive than gastric tumors.
- Tumors with a mitotic division rate of greater than 5 mitoses per 50 high-power fields (HPFs) tend to be more aggressive than those with lower mitotic rates.
A 2020 study showed that biological sex might be a factor in determining the prognosis of GIST, with male study participants with GIST demonstrating a tendency for higher risk of death than female study participants with GIST.7
The diagnosis of GIST in young adults and adolescents is extremely rare. A retrospective cohort study of individuals diagnosed with GIST between 2001 through 2013 with follow-ups through 2015 compared the surgical management outcomes of 392 adolescents with GIST to the surgical management outcomes of older adults over the age of 40 with GIST. The study indicated the increased likelihood of younger adults and adolescents undergoing surgical management of GIST compared to older adults who may require treatment using tyrosine kinase inhibitors due to advanced progression and spread of the disease. Surgical management overall is associated with longer overall survival and GIST-specific survival even in cases of metastasis.8
According to the American Cancer Society, it is unclear whether lifestyle choices lower the risk of GIST growth or recurrence, but general health may benefit from a balanced diet, regular exercise, keeping recommended appointments with physicians, not smoking, and taking all prescribed medications appropriately and routinely.9
Regardless of risk of recurrence or current staging, any person diagnosed with GIST should be monitored with CT scans of the abdomen and pelvis every 3 to 6 months to monitor growth or metastasis of existing tumors and check for recurrence after a resection has been performed.4
The 5-year survival rate for GIST ranges from 32% to 93% depending on staging and other factors. In the larger studies, the 5-year survival rate ranged from 50% to 60%.5 Based on individuals who received their GIST diagnosis between 2010 and 2016, the overall, relative 5-year survival rate was 83% compared with the general population.2,8 Information from the SEER database was utilized to calculate the 5-year survival rates for the varying SEER stages of GIST as follows:2
- Those with localized GIST tumors had a 5-year survival rate of 93%.
- Those with regional GIST tumors which spread to nearby tissues had a 5-year survival rate of 80%.
- Those with distant GIST tumors, which have metastasized to other body parts, had a 5-year survival rate of 55%.
In cases where GIST is far more advanced, palliative resections are performed to attempt to prolong survival. The median survival following a palliative resection is about 10 months with a 5-year survival rate of up to 10%.6 Survival rates for advanced GIST improved with administration of imatinib mesylate (GleevecⓇ).4,6
Breakthrough Cancer Treatments
Certain anti-tumor medications may be used in conjunction with surgical resection or for patients with nonresectable tumors. There are several different tyrosine kinase inhibitors (TKIs) that are used in the treatment of GIST. Each drug specifically targets genetic mutations that cause GIST.
Imatinib targets KIT and PDGFRA gene mutations, which account for the majority (80% to 90%) of individuals with GIST. Imatinib stabilizes or shrinks GIST tumors in the majority of cases. It works in 90% of cases and slows disease progression for an average of 2 years.4 Imatinib is the drug of choice to treat metastatic GIST with reported response rates and disease stabilization of 90% and a 9-year survival rate of 35%.4
Avapritinib (Ayvakit™) is a newer GIST therapy that targets metastatic cancer. It can be used to treat the cancerous GISTs caused by the rare exon 18 mutation in the PDGFRA gene, which does not respond well to other GIST therapies. Ripretinib (Qinlock™) was approved in 2020 for advanced GIST, which does not respond well to treatment with imatinib, sunitinib, and regorafenib. Ripretinib increased median progression-free survival rates significantly (15.1 months compared with 6.6 months in the placebo group) in phase 3 trials.10
Sunitinib (SutentⓇ) may work for patients who cannot tolerate imatinib or in cases where GIST has progressed. The rate of response and disease stabilization is over 50% with sunitinib, and the projected survival rate is over 2 years.4 Regorafenib (StivargaⓇ) is typically used to treat patients with GISTs that cannot be surgically resected and who no longer respond well to other treatments.3 Other medications that are used when GIST has progressed while the patient is taking imatinib and sunitinib include sorafenib (NexavarⓇ), dasatinib (SprycelⓇ), and nilotinib (TasignaⓇ).4 Use of these TKI therapies in conjunction with surgical management improve prognosis and life expectancy of individuals with GIST.
- Gastrointestinal stromal tumor stages and other prognostic factors. Cancer.org. Accessed June 17, 2021.
- Survival rates for gastrointestinal stromal tumors. Cancer.org. Accessed June 17, 2021.
- Aparicio T, Boige V, Sabourin J-C, et al. Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours. European Journal of Surgical Oncology. 2004;30(10):1098-1103. doi:10.1016/j.ejso.2004.06.016
- Shaw G. What you need to know about GIST. WebMD. Accessed June 17, 2021.
- Liu X, Chu K-M. Molecular biomarkers for prognosis of gastrointestinal stromal tumor. Clin Transl Oncol. 2019;21(2):145-151. doi:10.1007/s12094-018-1914-4
- Choti, MA. Gastrointestinal stromal tumors (GISTs): prognosis. Medscape. Accessed June 17, 2021.
- Rong J, Chen S, Song C, et al. The prognostic value of gender in gastric gastrointestinal stromal tumors: a propensity score matching analysis. Biol Sex Differ. 2020;11(1):43. doi:10.1186/s13293-020-00321-8
- Fero KE, Coe TM, Fanta PT, Tang CM, M JD, Sicklick JK. Surgical management of adolescents and young adults with gastrointestinal stromal tumors: a US population-based analysis. JAMA Surg. 2017;152(5). doi:10.1001/jamasurg.2016.5047
- Gastrointestinal stromal tumors: causes, risk factors, and prevention. Cancer.org. Accessed June 19, 2021.
- Lostes-Bardaji MJ, García-Illescas D, Valverde C, Serrano C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward.Ther Adv Med Oncol. 2021;13. doi:10.1177/1758835920986498
Article reviewed by Eleni Fitsiou, PhD, on July 1, 2021.