Minimally invasive surgery is feasible after preoperative chemotherapy for stage IV gastric cancer

Abstract Aim To elucidate the safety and feasibility of minimally invasive surgery (MIS) as conversion surgery after chemotherapy for stage IV gastric cancer, we compared the background characteristics and clinical courses of patients who underwent open conversion surgery (open group) versus MIS (MIS group). Methods We included 94 consecutive patients with stage IV gastric cancer who received chemotherapy followed by conversion surgery gastric resection from January 2011 to October 2019 at the Osaka International Cancer Institute in this analysis. Results The open group included more patients who had macroscopic peritoneal metastasis and required splenectomy. However, other background characteristics, including preoperative chemotherapy duration, were comparable. The MIS group had significantly longer operative time (266 vs 339 minutes, P = .0039) and less operative blood loss (520 vs 10 mL, P < .0001). The incidence of postoperative complication of Clavien‐Dindo grade II or higher was non‐significantly lower (24.5% vs 9.8%, P = .058) and length of postoperative hospital stay was significantly shorter in the MIS group (12 vs 8 days, P < .0001). Even though the open group included more patients with more advanced (ypT4a or higher, or N3) disease, the MIS group had better recurrence free survival and overall survival (OS). Multivariate analysis revealed that N status (hazard ratio [HR], 4.39; 95% confidence interval [CI], 2.18‐12.26; P < .0001) and T status (2.11; 1.05‐4.36; P = .036) were independent prognostic factors for OS. MIS was not a negative prognostic factor for OS (HR, 0.44; 95% CI, 0.15‐1.10; P = .081). Conclusion MIS can be safely performed as conversion surgery following chemotherapy for stage IV gastric cancer.


| INTRODUC TI ON
Gastric cancer is the third most common cause of cancer death throughout the world. 1 Pathological tumor staging is the most important prognostic determinant for patients with gastric cancer. 2 In particular, the prognosis of stage IV gastric cancer remains dismal, 3 despite recent improvements in cancer diagnosis and multimodal treatment. Therefore, a new approach for stage IV gastric cancer is needed to achieve further improvements in gastric cancer treatment.
Conversion surgery for gastric cancer was defined by Yoshida et al as surgical treatment aiming at R0 resection after chemotherapy for tumors that were originally unresectable or marginally resectable for technical or oncological reasons. 4,5 Conversion surgery has received much attention recently from surgical oncologists because favorable treatment outcomes have been obtained in some cases initially diagnosed as stage IV gastric cancer. [6][7][8] However, several challenging issues regarding conversion surgery for gastric cancer remain, such as (a) the optimal chemotherapy regimen, (b) optimal duration of preoperative chemotherapy, (c) optimal approach and procedure for conversion surgery, and (d) recommended postoperative chemotherapy after conversion surgery.
In terms of the optimal approach and procedure, minimally invasive surgery (MIS), such as laparoscopic gastrectomy and robotic gastrectomy, has been recognized as a good treatment option for early gastric cancer that is associated with lower postoperative complication rates, less pain, and early recovery. [9][10][11] Patients with more advanced cancer have also benefited from MIS with comparable postoperative morbidity [12][13][14][15] and long-term outcomes 16 as with the conventional open approach. However, there was no reports to elucidate the effectiveness of MIS as conversion surgery as surgical treatment following chemotherapy for stage IV gastric cancer. The purpose of this study was to evaluate the safety and clinical impact of MIS as conversion surgery after chemotherapy for stage IV gastric cancer.

| Preoperative chemotherapy
All 94 patients in this study originally had advanced gastric cancer with peritoneal, hepatic, or distant metastases. They all received preoperative chemotherapy regimens, which were divided into the following three groups: (a) triplet regimen, (b) platinum-based doublet ± trastuzumab, and (c) regimens that contained intraperitoneal (IP) chemotherapy.

| Surgery
When tumor response was observed with computed tomography (CT), which was performed after every two cycles of chemotherapy, curative surgery was attempted. The surgical procedure and type of lymph node dissection used for conversion surgery depended on the site of primary tumor and curability. For R0 resection, para-aortic lymph node dissection (D3) or partial hepatectomy was attempted if the metastatic tumor was still detected TA B L E 1 Preoperative chemotherapy regimens and duration (n = 94)   18 Complications were defined as those that were CD grade II or higher. Complications that were Grade IIIa or higher were considered severe complications.

| Statistical analysis
This was a single-center retrospective observational study.
Continuous variables were expressed as medians (range). The

| Preoperative chemotherapy
Preoperative chemotherapy regimens and durations were summarized in Table 1   Note: Gastric cancer staging and histological evaluation after preoperative chemotherapy were based on the Japanese classification of gastric carcinoma, third English edition. 17

| Background characteristics and operative factors of the open and MIS groups
Abbreviations: CI, confidence interval; CR, complete response; HR, hazard ratio; IP, intraperitoneal chemotherapy; IP, intraperitoneal chemotherapy; MIS, minimally invasive surgery; OS, overall survival; T or D, Triplet or platinum-based doublet ± trastuzumab; TG, total gastrectomy.

| Postoperative complications and clinical course
The incidence of postoperative complications of CD grade II or higher was lower in the MIS group than in the open group (24.5% vs 9.8%; P = .058) but the difference was not statistically significant.
None of the patients in the MIS group developed severe postoperative complications of CD grade III or higher. There was no significant difference in the distribution of complications or their severity between the two groups. Length of hospital stay after conversion surgery was significantly shorter in the MIS group (12 vs 8 days; P < .0001). There was no mortality within 90 days after surgery in either group (Table 3).

| Pathological findings and postoperative chemotherapy
Pathological findings, histological evaluation of chemotherapy effects, and postoperative chemotherapy were presented in Table 4.
The open group included more aggressive cases with ypT4a or higher

| Survival
Survival analysis was performed after a median observational pe-  Figure 1D). This tendency was maintained even when the patients were separately compared among category 1 ( Figure 1E) and category 2-4 ( Figure 1F), and difference was more significant in category 1 in which patients who received preoperative chemotherapy as neoadjuvant setting.

| Impact of MIS on OS
To evaluate the impact of MIS on OS in patients who underwent conversion surgery gastrectomy after preoperative chemotherapy for stage IV gastric cancer, we used Cox proportional hazards models to stratify by cancer stage (   In conclusion, our results suggest that MIS can be safely performed as conversion surgery following after chemotherapy for stage IV gastric cancer.

CO N FLI C T O F I NTE R E S T
Authors declare no conflicts of interest for this article.