I. Principles of Surgery
The standard principle of treatment for limited GIST is complete resection of the tumor.
Most GIST nodules located in the esophagus-gastric or duodenum ≤2 cm are low-risk GISTs and therefore only regular follow-up is required for these patients; if the nodule grows in size during follow-up, biopsy or resection may be considered. For nodules >2 cm, the standard treatment is biopsy or resection. GIST located in the rectum (or recto-vaginal space) requires complete intervention (biopsy or resection) regardless of tumor size because of the high potential risk of the disease itself.
Laparoscopic surgery is not recommended routinely because of its tendency to cause tumor rupture leading to abdominal implantation. If the tumor is ≤ 2 cm in diameter, laparoscopic resection at an experienced center can be considered. This is done according to the 2007 Consensus on Surgical Treatment of Gastrointestinal Mesenchymal Tumors for surgical and marginal requirements. Intraoperative “extraction bag” is recommended to avoid tumor rupture and dissemination. For larger tumors, laparoscopic surgery is not recommended.
Achieving R0 resection is the goal of all surgeries. If the initial surgery is only an R1 resection, a second surgery may be considered if it is expected to be easy to perform and the risk is manageable without causing major functional organ damage. If secondary surgery is likely to cause major functional organ damage, then secondary surgery is not recommended, especially for low-risk patients, and there is no evidence to support a worse prognosis for patients with R1 resection than for patients with R0 resection.
Principles of tumor-free operation: GIST is usually brittle in texture, and especially large tumors often have intratumoral hemorrhage or necrosis. Preoperative or intraoperative tumor rupture is one of the main reasons for poor prognosis. Therefore, tumor rupture and intraoperative dissemination should be avoided along with complete resection of the tumor.
Lymph node metastasis is rare in GIST, and routine debulking is not necessary unless there are clear signs of lymph node metastasis.
Biopsy: GIST tumors are soft and brittle, and biopsy may cause tumor bleeding or increase the risk of tumor dissemination.
Preoperative biopsy is not recommended if the tumor can be completely resected.
Biopsy is necessary for larger lesions where it is anticipated that combined multivisceral surgery may be required or neoadjuvant therapy is planned. Definitive diagnosis to plan the best treatment plan.
Incidental finding of a tumor suspected to be GIST. biopsy may be considered in order to exclude other diseases for a definitive diagnosis (e.g. lymphoma)
Ultrasound endoscopy-guided biopsy ( multi-hole needle aspiration biopsy ) is recommended. The intra-abdominal contamination due to puncture is negligible if performed in a standardized manner.
The physician should fully estimate the risk before biopsy and apply caution for deep sites, highly susceptible to bleeding, and cystic lesions.
II. Neoadjuvant treatment: The operation should ensure minimal damage and preserve organ function as much as possible. If preoperative evaluation is uncertain that the surgery can achieve R0 resection, or/and requires combined multi-organ surgery, or if a high risk of postoperative comorbidity is expected, preoperative Gleevec (imatinib mesylate) neoadjuvant therapy can be considered. For tumors in specific sites, such as the rectum or rectovaginal space, where the risk of local recurrence is high and the associated organ function is estimated to be severely affected postoperatively (e.g., artificial anus, etc.), consider expanding the indication population for neoadjuvant therapy.
Preoperative treatment with Gleevec (imatinib mesylate) until maximum tumor response occurs, usually 6-12 months before surgery. PET or PET-CT helps to assess the efficacy of Gleevec (imatinib mesylate) early and avoid delaying surgery in cases where Gleevec (imatinib mesylate) is ineffective. Once disease progression is confirmed, immediate discontinuation of drug therapy and surgical intervention is required.
Gleevec (imatinib mesylate) should be discontinued for 1-2 weeks prior to surgery to allow gastrointestinal edema to decrease and bone marrow hematopoietic function to recover; Gleevec (imatinib mesylate) therapy should be resumed as soon as the patient can tolerate oral medication after surgery.
Preoperative drug therapy for patients with recurrent metastases cannot be called neoadjuvant therapy.
III. Adjuvant therapy: The risk of recurrence after GIST surgery is real. Especially for patients with intermediate – high risk. The risk of recurrence of GIST should be carefully assessed after surgery based on tumor size, pathological nuclear split images, site of the primary tumor, and intraoperative conditions (tumor rupture, hemorrhage, necrosis, infiltration, lymph node metastasis signs).
The international multicenter, randomized, placebo-controlled phase 3 clinical trial ( ASOCOG Z9001 ) demonstrated significantly improved progression-free survival in patients treated with adjuvant therapy with gleevec (imatinib mesylate) for 1 year after complete postoperative resection of tumors ≥3 cm in diameter compared with controls, with no significant difference in overall survival.
The 36-month follow-up of the Z9001 trial showed that even for 3-6 cm tumors, adjuvant therapy with Gleevec (imatinib mesylate) showed a statistically significant difference in RFS (91.7% vs. 83.7%). A national multicenter study also confirmed the benefit of adjuvant therapy with Gleevec (imatinib mesylate) in patients with intermediate-to-high-risk GIST. Combining clinical practice experience and available clinical trial results, the panel agreed that intermediate-to-high-risk patients are an indication population for adjuvant therapy.