Tumor Size is Associated with Long-Term Outcomes after Resection of Gastric Gastrointestinal Stromal Tumors

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Abstract

Introduction

Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesodermal origin in the gastrointestinal (GI) tract [1]. GISTs originate from the interstitial cells of Cajal in the muscular layer of the GI tract. Activating mutations in oncogenes such as KIT and PDGFRA are known to be associated with the development of GISTs [2,3]. GISTs account for less than 1% of all malignant tumors in the GI tract, and while they occur most commonly in the stomach (70%), they can occur anywhere in the GI tract, including the small intestine (20–30%) or the rectum/colon (10%) [4]. The standard treatment for GISTs, including gastric tumors, is surgical resection. The aim of surgery is complete resection to ensure that no tumor is left in the resection margin and to avoid rupture of the tumor, which can increase the risk of recurrence [5]. However, the clinical course after surgical resection varies greatly. While GISTs can have a very slow, benign course, they often progress very rapidly even after meticulous surgical resection [6,7]. This is because the prognosis for gastric GISTs is affected by tumor size and mitotic index [8,9]. To date, there have been almost no reports on the long-term prognosis, including recurrence, after surgical resection of gastric GISTs. Therefore, in this study, we aimed to analyze the long-term therapeutic outcomes and prognoses of surgically resected gastric GISTs according to tumor size.

Materials and Methods

Results

Patients’ demographic characteristics

A total of 269 patients underwent surgery for gastric GIST, of whom 69 were excluded because they had simultaneous gastric adenocarcinoma, which would have confounded the analysis of recurrence rates. There were 200 patients in the final analysis. Based on their pathological results, 38 patients were classified in the very low risk group, 98 in the low risk group, 45 in the intermediate risk group, and 19 in the high risk group (Fig. 1). The patients’ mean age was 60.8 ± 11.7 years, and there were was a predominance of females (127 patients). There were 6 patients with a tumor size <1 cm (3%), 37 with a tumor size of 1–2 cm (18.5%), 104 with a tumor size of 2–5 cm (52%), and 53 with a tumor size of >5cm (26.5%). The mean follow-up duration was 67 months (0.2–200 months) (Table 1).

Fig. 1.

Recurrence risk classification

The very low, low, intermediate, and high risk groups were classified based on the 2007 JNCCN. Sixty nine patients who had simultaneous gastric adenocarcinoma were excluded.

Table 1.

Clinical characteristics of the 200 patients with gastric GIST

Tumor recurrence

During an average follow-up period of 67 months (0.2–200 months), recurrence was observed in 7 patients (3.5%). There was 1 case of recurrence in the very low risk group in a patient with a tumor size of 1–2 cm, and 2 cases in the very low risk group in patients with tumor sizes of 2–5 cm. In the high risk group, there were 3 cases of recurrences in patients with tumors >5 cm (5.7%). Table 2 shows the clinical characteristics of the 7 patients who developed a recurrence. The most common sites of recurrence were the stomach and liver. All the patients were subsequently treated with imatinib. There was 1 death during the follow-up period, of a patient in the high risk group with a tumor size of ≥10cm, and the cause of death was GI bleeding due to GIST. The 5-year recurrence-free survival rates were 100% in the very low risk group, 98.9% in the low risk group, 95.5% in the intermediate risk group, and 86.7% in the high risk group; these differences were statistically significant (log-rank test, p <0.05) (Fig. 2).

Table 2.

Characteristics of the patients that developed a recurrence after surgical resection

Fig. 2.

The 5-year recurrence-free survival rates according to risk groups

The recurrence-free survival rates in the very low, low, intermediate, and high risk groups were 100%, 98.9%, 95.5%, and 86.7%, respectively. Statistical analysis showed a significant lower recurrence-free survival rate in the high risk group (log-rank test, p <0.05

Discussion

This study was a retrospective analysis of recurrence in patients who underwent surgery for gastric GIST. Compared to overseas studies, in which the mean age of gastric GIST patients was around 63 years and there were more male patients than female patients [10,11], the mean age in our study was 60.8 years, and there was a predominance of female patients. Other Korean studies have also reported younger patient ages (around 60 years on average) and more females than overseas studies [12,13].

The first aim of treatment for gastric GIST is complete surgical resection with no infiltration of the margin. The desired resection margin has been reported to be 1–2 cm [14]. However, recent studies have reported that extensive resection to ensure a wide margin is not necessary, and is unrelated to good surgical outcomes [15,16]. Therefore, the objectives of gastric GIST surgery have shifted recently toward only complete resection with a clear margin, and since lymph node metastasis is extremely rare, lymph node dissection is not generally performed [7].

The postoperative recurrence rates of gastric GIST reported in Western studies is 17–24% [17,18]. However, studies from Korea and Japan report lower postoperative recurrence rates. Similarly, we observed a postoperative recurrence rate of 3.5%, albeit in a cohort with a large number of patients in the very low and low risk groups. Other Korean studies have also reported similar recurrence rates. Yang et al. [19] reported recurrence in 6 out of 105 patients (5.7%) after surgical resection, and Kim et al. [7,20] reported postoperative recurrence rates of 2.7% and 4.8%. Japanese studies have shown even lower recurrence rates; for example, Honda et al. [21] reported recurrence in only 1 out of 78 patients (1.3%) after laparoscopic surgery for gastric GIST. These low recurrence rates are thought to be due to recent improvements in surgical techniques and early diagnosis. In particular, Korea and Japan have high rates of early gastric cancer endoscopic examinations for early detection are performed more often than in Western countries. As a result, smaller GISTs are more likely to be found.

The 5-year recurrence-free survival rates in the very low and low risk groups in our study were 100% and 98.9%, respectively, which were similar to other studies [5]. In addition, there were no deaths during the follow-up period in the low risk group or below, which is also consistent with other studies [22]. However, the high risk group showed a low 5-year recurrence-free survival rate of 86.7%, and there was also a case of death due to GIST-related bleeding in the high risk group. This is also the same as other studies, with high risk GIST patients showing high recurrence rates and poor prognoses; the 5-year survival rate after complete resection of high risk GIST has been reported in the range of 35–70% [23-25].

Our study had several limitations. First, as a retrospective study, the numbers of patients in the very low, low, intermediate, and high risk groups are all different, and the follow-up duration and timing of follow-up examinations also differ. Second, there were not many patients who underwent endoscopic ultrasound to determine the risk of gastric GIST. In particular, 1 case of recurrence was observed even among patients with a tumor size of <2cm, which is generally managed by monitoring without surgery. Had the internal appearance of the tumor been inspected by endoscopic ultrasound, it might have been possible to analyze the risk of recurrence in more detail.

In conclusion, although the recurrence rate after complete resection of gastric GIST is very low, the high risk group requires thorough postoperative follow-up to monitor for recurrence. In addition, even in the very low risk group, with tumor size <2cm and low mitotic index, cases of recurrence do occur, and so regular postoperative follow-up is essential.

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