Minimally invasive surgery (MIS) for resection of gastrointestinal cancers has been increasingly utilized due to the enhanced recovery with equivalent oncologic outcomes [1, 2]. Even though most data supporting this are retrospective, randomized controlled trials are supporting these findings as well [3, 4].

Gastrointestinal stromal tumors (GIST) represent relatively rare neoplasms, and therefore the conduction of randomized trials on surgical outcomes challenging. However, retrospective data support comparable outcomes between open and MIS with faster recovery associated with the latter [2, 5]. Patients operated via MIS seem to have smaller tumors which is likely a result of patient selection [5]. Outcomes of MIS in challenging scenarios (such as large tumors ≥ 10 cm or following neoadjuvant treatment) have not been investigated.

The National Cancer Database provides an ideal database to examine the national trends and outcomes of MIS for GIST tumors as it captures a robust collection of nationwide oncologic data. In this report, we attempted an in-depth analysis of surgical outcomes of MIS versus open surgery for GISTs of the stomach and small bowel. Our first aim was to examine the trends and outcomes of MIS in GIST tumors. Our second aim was to examine whether enhanced outcomes of MIS are preserved in cases of large tumors (≥ 10 cm) or when patients have undergone neoadjuvant treatment.

Methods

The National Cancer Database (NCDB) is a collaborative effort of the American College of Surgeons Commission on Cancer (CoC) and the American Cancer Society reporting on nationwide data from over 1500 hospitals and approximately 70% of all newly diagnosed cancer cases [6].

Institutional Review Board approval was not required for this study as the NCDB data is de-identified and the study was granted exempt status from the Texas Tech University Health Sciences Center IRB. For the purpose of this study we reviewed the relevant Participant User Files (PUF) for stomach and small bowel during the period of 2010–2016 who had a histologic diagnosis of GIST. This was the most recent PUF released at the time of completion of this project.

Patient data

Patient data analyzed included demographics (age, gender, race), socioeconomic characteristics (median income, insurance type, education), institution characteristics (facility type), and comorbidities as expressed by the Charlson-Deyo comorbidity index.

Surgeries and postoperative outcomes

The designated surgical approach (open, robotic, laparoscopic) has been available since 2010. The surgical margin status was coded as no residual tumor (R0), microscopic residual tumor (R1), macroscopic residual tumor (R2), residual tumor (not otherwise specified), or margin cannot be assessed/unknown. Postoperative outcomes examined included unplanned hospital readmission at 30 days, 90-day mortality and survival. NCDB records overall survival rather than disease specific survival. For examination of survival outcomes we included only patients who had follow-up of at least 90 days.

Statistical analysis

Quantitative variables were described using mean, standard deviation (SD), median, and inter—quartile range (IQR). Categorical variables were described using frequency and proportions. Unpaired T-test, Chi-squared test, and Fisher’s Exact test were used to assess differences and associations for selected cofactors. A univariate relative risk regression was conducted to assess the relationship between neoadjuvant treatment and other variables of interest. Due to multiple facility ID’s a clustering effect was compensated for within the model. These estimates were reported as relative risk (RR) along with their 95% confidence interval (CI). p values less than 5% were considered statistically significant. Propensity score matching 1:1 was utilized to compare the outcomes of minimally invasive versus open surgery after controlling for age, gender, ethnicity, insurance status, social economic status, Charlson-Deyo score, and tumor size. All analyses were carried out using STATA V.15.

Results

Clinicopathologic characteristics

From 2010 to 2016, 8923 patients with stomach GISTs and 3683 patients with small bowel GISTs were reviewed. During the time period, MIS became the prevalent modality for gastrectomies (2010: robotic: 2.4%, laparoscopic: 26.1%, open: 71.5% vs. 2016: robotic: 9.6%, laparoscopic: 48.8%, open: 41.6%; p < 0.001), whereas the increase in MIS was much less for enterectomies (2010: robotic: 1%, laparoscopic: 17.3%, open: 81.6% vs. 2016: robotic: 3.9%, laparoscopic: 27.2%, open: 68.9%; p < 0.001). Table 1 illustrates the clinicopathologic characteristics of this patient cohort according to tumor location.

Table 1 Clinicopathologic characteristics of 12,606 patients with gastrointestinal stromal tumors of the stomach and small bowel stratified according to tumor location (NCDB, 2010–2016)
Full size table

Since MIS was utilized more often for gastric resections we performed a separate analysis of the 8923 patients with stomach GISTs according to surgical modality (Table 2). MIS was utilized more frequently in younger patients (mean age 65.2 vs. 66.1; p < 0.001) and females (53.8% vs. 50.7%; p = 0.003). MIS was utilized more often for smaller tumors (tumor size 0–5 cm in 72.3% of MIS and 47.1% of open; p < 0.001) and was associated with negative surgical margins (90% vs. 87.8% for open; p < 0.001), less readmissions (2.15% vs. 4.1% for open; p < 0.001) and decreased 90 day mortality (1.3% vs. 2.9% for open; p < 0.001).

Table 2 Clinicopathologic characteristics of 8923 patients with gastrointestinal stromal tumors of the stomach stratified according to surgical modality (Open, MIS: minimally invasive surgery, NCDB, 2010–2016)
Full size table

Use of neoadjuvant therapy

Information about the use of neoadjuvant therapy was available for 12,459 patients. Overall, it was used in a small portion of patients (6.2% of small bowel and 7.2% of stomach GISTs). A comparison of the patients who received neoadjuvant therapy versus patients who did not receive neoadjuvant therapy is illustrated in Table 3. Patients who underwent neoadjuvant treatment had lower Charlson/Deyo comorbidity scores, were more often privately insured and were treated at an academic/research facility.

Table 3 Use of Neoadjuvant therapy in GIST tumors of the stomach and small bowel
Full size table

Neoadjuvant therapy was utilized more often for larger tumors (tumor size ≥ 10 cm for 44.6% of neoadjuvant cases versus 15% of non neoaduvant; p < 0.001). Use of neoadjuvant therapy was associated with higher percentage of positive surgical margins. Neoadjuvant treatment was utilized less often in MIS patients.

Survival outcomes

We investigated whether the utilization of MIS compromises long-term outcomes in patients who underwent neoadjuvant therapy or harbored tumors ≥ 10 cm.

Even though patients who underwent neoadjuvant treatment had overall worse survival both for stomach and small bowel GISTs, the use of minimally invasive surgery in this setting had comparable survival outcomes to open surgery. Figure 1 represents the corresponding Kaplan–Meier curve for stomach GISTs as the number of MIS for small bowel GISTs was small.

Fig. 1
figure 1

Minimally invasive surgery was associated with comparable overall survival to open surgery in stomach GIST patients who underwent neoadjuvant treatment (median OS: median OS not reached for any of the groups, p = 0.3)

Full size image

Similarly, the use of MIS did not compromise long-term outcomes in resection of tumors ≥ 10 cm. Figure 2 illustrates the relevant Kaplan–Meier curve for stomach GISTs ≥ 10 cm.

Fig. 2
figure 2

Minimally invasive surgery was associated with comparable overall survival to open surgery in patients with stomach GISTs with a size ≥ 10 cm (median OS: median OS not reached for any of the groups, p = 0.3)

Full size image

Matched cohorts

We examined the postoperative outcomes of patients who underwent MIS vs open resections for GIST tumors of the stomach and small bowel after matching them 1:1 for age, gender, ethnicity, insurance status, social economic status, Charlson-Deyo score, and tumor size (Table 4). Overall, for stomach GIST, 3148 patients who underwent MIS were matched with 3148 patients who underwent open surgery, whereas for small bowel GIST 857 patients who underwent MIS were matched with 857 patients who underwent open surgery. The improved outcomes of MIS for stomach GIST were maintained in the matched cohorts (90 day mortality: MIS: 1.4% vs. Open: 2.6%; p = 0.002, readmission within 30 days: MIS: 2.2% vs. Open: 4%; p < 0.001, Table 4. MIS was associated with decreased risk of death vs. open surgery (HR 0.6, 95% CI 0.54–0.74; p < 0.001). The outcomes for small bowel GIST were similar between open and MIS (Table 4).

Table 4 Postoperative Outcomes in patients with Gastrointestinal Stromal Tumors of the Stomach and Small Bowel after propensity score matching (NCDB, 2010–2016)
Full size table

Discussion

In this report utilizing data from the NCDB, we found an increase in minimally invasive resections for gastric and small bowel GISTs over the period 2010–2016. The greatest increase occurred for gastrectomies where MIS is currently the predominant surgical modality. Postoperative outcomes were improved with minimally invasive resections without compromising patient survival. We found that MIS did not compromise long-term outcomes after stratification of results by the receipt of neoadjuvant therapy and for tumors ≥ 10 cm; therefore MIS is a safe modality even in these challenging cases.

Population-based studies and meta-analysis data on GIST tumors undergoing MIS have shown improved short-term and equivalent long-term outcomes compared to open surgery [2, 5]. Similar findings have been reported for adenocarcinomas of esophagus, stomach, pancreas, colon, and rectum [1]. There is obvious selection bias of patients who undergo minimally invasive resections. Not surprisingly, in the current report, larger tumors are still operated in an open fashion even though we showed that even in tumors ≥ 10 cm MIS does not compromise long-term outcomes. Others have shown that laparoscopic resections are associated with improved disease free and overall survival for gastric GIST tumors ≥ 5 cm [7].

MIS approaches are frequently not used in the setting of neoadjuvant treatment. However, neoadjuvant systemic therapy is increasingly being utilized for gastrointestinal cancers such as stomach, rectal, and pancreatic adenocarcinomas [8,9,10]. For GIST tumors it is oftentimes used to reduce surgical morbidity usually due to unfavorable tumor location or size [11, 12]. In the current report even though MIS was less often used in this setting it did not seem to compromise patient survival. Therefore, it represents a safe approach in this setting.

Even though the NCDB maintains the highest quality control of data, reporting errors can still occur. Furthermore, patient exact comorbidities and body mass index are not available; similarly surgeon experience and radiologic data can affect the decision to use MIS and are lacking. Even though we utilized the most recent PUF released at the time of completion of this study still data for the most recent years were not available. However, even with the above limitations the NCDB illustrates the national outcomes in cancer care and provides unique oncologic data of high quality among population-based databases.

Conclusion

There is an increased utilization of minimally invasive surgery for GIST tumors especially of the stomach where it represents the prevalent surgical modality and less often for small bowel GISTs. Minimally invasive surgery is associated with improved short-term outcomes and does not compromise patient survival even in challenging scenarios such as the receipt of neoadjuvant treatment or the presence of tumors ≥ 10 cm.