Gastrointestinal Stromal Tumors (GISTs) Guidelines

Updated: May 24, 2022
  • Author: Michael A Choti, MD, MBA, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines

Guidelines Summary

WHO Classification of Tumors

In 2013 the World Health Organization released an update of its 2002 classification system for tumors of the soft tissue and bone.  The update incorporated more detailed cytogenetic and molecular data into the classifications. Gastrointestinal stromal tumors (GISTs) have been added in the update, with three subtypes [82] :

  • Benign
  • Uncertain malignant potential
  • Malignant

Tumor Grading Systems

The French Federation of Cancer Centers Sarcoma Group (FNCLCC) system  [83] and the National Cancer Institute system are most commonly used for grading soft tissue sarcomas. [84]  Both are three-grade systems. The FNCLCC is based on tumor differentiation, tumor necrosis and mitotic activity, while the NCI system bases the evaluation on histology, location and tumor necrosis. In comparison studies, the FNCLCC has shown slightly better ability to predict metastasis development and mortality.

The  American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) grades GISTs separately from other sarcomas, using a two-grade system based on mitotic rate, as follows [39]

  • Low: ≤5 mitoses per 5 mm 2, or per 50 high-power field (HPF)
  • High: > 5 mitoses per 5 mm 2, or per 50 HPF

Tumor Staging

For staging of GISTs, both the NCCN and the European Society for Medical Oncology (ESMO) guidelines follow the tumor-node-metastasis (TNM) classification of the AJCC/UICC. Anatomic stage/prognostic groupings for GIST are detailed in Table 4, below. [51]

Table 4. Staging of Gastric Gastrointestinal Stromal Tumors (Open Table in a new window)

Stage

T

N

M

Grade

IA

T1 or T2

N0

M0

Low

IB

T3

N0

M0

Low

II

T1

N0

M0

High

T2

N0

M0

High

T4

N0

M0

Low

IIIA

T3

N0

M0

High

IIIB

T4

N0

M0

High

IV

Any T

N1

M0

Any grade

Any T

Any N

M1

Any grade

For description of GIST TNM designations, see Gastrointestinal Stromal Tumors Staging.

Diagnosis

The NCCN guidelines for GISTs recommend evaluation and management, prior to initiation of therapy, by a multidisciplinary team with expertise and experience in sarcoma. Abdominal/pelvic CT scan with contrast, with or without MRI, is also indicated and chest imaging should be considered. Very small gastric GISTs (< 2 cm) may be evaluated with endoscopic ultrasound-guided fine-needle aspiration; for GISTs 2 cm or larger, endoscopy with or without ultrasound may also be indicated in select patients. [39]

Genetic testing for KIT and PDGFRA is a strong recommendation when medical therapy is being considered. Identification of certain specific KIT and PDGFRA mutations helps predict responsiveness to imatinib and the possible benefit of a higher imatinib dose.

In patients with GISTs that lack KIT or PDGFRA mutations, immunohistochemistry (IHC) for SDHB deficiency, for gastric tumors, and succinate dehydrogenase (SDH) mutation testing for SDHB-deficient tumors is indicated. Germline loss-of-function mutations within the SDH gene subunits SDHB, SDHC, and SDHD have been identified in individuals with GISTs associated with Carney-Stratakis syndrome, an autosomal dominant familial syndrome characterized by a predisposition to GISTs and paragangliomas. In addition, next-generation sequencing (NGS) testing for alternative driver mutations (eg, BRAF, NF1, NTRK, and FGFR fusions) should be performed, as it may identify tumors that could respond to targeted therapy. [39]

Treatment

NCCN treatment recommendations for localized resectable disease include the following [39] :

  • Surgical resection is recommended for gastric tumors < 2 cm with no high-risk features (eg, irregular border, cystic spaces, ulceration, echogenic foci, heterogeneity) and for known or suspected GISTs that are resectable with minimal morbidity.
  • Consider periodic endoscopic or radiographic surveillance for gastric GISTs < 2 cm with no high-risk features.
  • For GISTs that are resectable but with significant morbidity, consider neoadjuvant imatinib, or avapritinib for GISTs with PDGFRA exon 18 mutations that produce insensitivity to imatinib (eg, the D842V mutation). Follow with surgery if feasible.
  • After complete resection, treat with adjuvant imatinib in patients at intermediate or high risk of recurrence; continue imatinib in patients who received it preoperatively.
  • Follow with history and physical and abdominal/pelvic CT every 3-6 months for 5 years, then annually.

ESMO guidelines recommend that patients with small esophagogastric or duodenal nodules < 2 cm undergo endoscopic ultrasound assessment and then annual follow-up, reserving excision for patients whose tumor increases in size or becomes symptomatic. For small rectal nodules, however, the ESMO guidelines recommend biopsy/excision after ultrasound assessment, regardless of tumor size. In addition, all nodules 2 cm or larger require biopsy. ESMO guidelines discourage a laparoscopic approach for resection of large tumors. [25]

The NCCN recommends tyrosine kinase inhibitor (TKI) therapy for unresectable, recurrent, or metastatic disease, as follows (all category 1) [39] :

  • Imatinib
  • After assessment of therapeutic effect, resection may be considered or imatinib may be continued if resection is not feasible
  • Sunitinib for patients with imatinib-resistant GIST
  • Regorafenib for patients with disease progression on imatinib and sunitinib
  • Ripretinib for patients with disease progression on imatinib, sunitinib, and regorafenib
  • TKI therapy should be continued as long as patients experience clinical benefit (response or stable disease)
  • Continuation of TKI therapy lifelong for palliation of symptoms is an essential component of best supportive care