Gastrointestinal stromal tumor (GIST) is a type of cancer that originates in the digestive tract, specifically from the interstitial cells of Cajal, which regulate gut movement. Determining the extent of the disease, a process known as staging, is a standard practice in cancer care. However, GIST staging differs significantly from the systems used for most other cancers, necessitating a unique approach to assess its progression and guide treatment.
Unique Approach to GIST Staging
GIST does not use the widely known TNM (Tumor, Node, Metastasis) staging system, which categorizes cancers based on tumor size, lymph node involvement, and distant spread. Instead, GIST staging relies on distinct prognostic factors that are highly specific to this tumor type. These factors include the tumor’s size, its mitotic count, and its anatomical location within the digestive system.
Tumor size is a straightforward measurement, expressed in centimeters. The mitotic count refers to the number of dividing cells observed under a microscope within a specific area of the tumor, reported as the number of mitoses per 50 high-power fields (HPFs). A higher mitotic count generally indicates a faster-growing tumor. Pathologists assess this by examining a biopsy or surgically removed tissue.
The location of the tumor also plays a role in GIST staging. For instance, GISTs originating in the stomach behave less aggressively than those of similar size and mitotic count found in the small intestine. Other locations, such as the esophagus, colon, or rectum, also have different implications for prognosis.
Understanding GIST Risk Assessment
The individual factors of tumor size, mitotic count, and location are combined to determine a patient’s risk of GIST recurrence or progression, rather than assigning a numerical stage. This risk assessment categorizes GISTs into different groups, guiding subsequent management decisions. Established guidelines, such as those developed by the National Institutes of Health (NIH) or the modified Fletcher criteria, define these risk categories.
The NIH-Fletcher criteria classify GISTs into categories such as very low, low, intermediate, and high risk:
- Very low-risk: Less than 2 cm with fewer than 5 mitoses per 50 HPFs.
- Low-risk: Between 2 and 5 cm with fewer than 5 mitoses per 50 HPFs.
- Intermediate-risk: Less than 5 cm with 6-10 mitoses per 50 HPFs, or 5-10 cm with fewer than 5 mitoses per 50 HPFs.
- High-risk: Larger than 5 cm with more than 5 mitoses per 50 HPFs, any tumor larger than 10 cm regardless of mitotic rate, or any size with more than 10 mitoses per 50 HPFs.
The modified NIH criteria, also known as Joensuu risk criteria, further incorporate tumor rupture as a high-risk factor. For instance, gastric GISTs larger than 10 cm with a high mitotic index (more than 5 mitoses per 50 HPFs) carry a high risk of progression, similar to GISTs in other locations.
Significance of Staging for Treatment Planning
The risk category determined through GIST staging has direct implications for patient management and treatment planning. The extent of surgical resection is influenced by the tumor’s size and location, aiming for complete removal while preserving organ function where possible.
The risk assessment also guides decisions regarding adjuvant therapy, which is treatment given after surgery to reduce the chance of recurrence. For patients with high-risk GISTs, targeted therapy with medications like imatinib (Gleevec) is often recommended. Imatinib, a tyrosine kinase inhibitor, works by blocking specific signaling pathways that promote tumor growth, and it is prescribed for three years in high-risk cases. This duration has shown benefit in improving recurrence-free survival and overall survival.
In some situations, imatinib may also be used before surgery, known as neoadjuvant therapy, to shrink the tumor and make it easier to remove. Accurate risk assessment also influences the frequency of follow-up appointments and monitoring for any signs of recurrence. This personalized approach to treatment, based on the specific characteristics and risk profile of each GIST, optimizing outcomes and providing an informed prognosis.