Baseline demographic and clinicopathologic characteristics
A total of 162 patients were included in the study, including 25 cases in the PCIT group and 137 cases in PCT. A significant difference was observed in age between the two groups [median (IQR) age of 58 (37.5,67) years in the PCIT group vs. 64 (54,69) years in the PCT group, p=0.035]. The other demographic and clinicopathologic characteristics were comparable between the two groups, including gender, BMI, ASA score, comorbidity, abdominal surgery, tumor long and short diameters, clinical stage, RECIST criteria, preoperative regimen, preoperative cycle, Borrmann type, adverse event, surgery approach and the extent of gastrectomy. The detailed demographic and clinicopathologic characteristics of the two groups are provided in Table 1.
Preoperative therapy regimen, response rate, and related adverse effects
The routine regimens of PCT were one-, two- or three-drug regimens based on fluorouracil. The treatment regimens of PCIT included the use of anti-PD-1 antibodies, or anti-CTLA-4 antibodies in conjunction with the above chemotherapy regimens.
The ORR in the PCIT group was 36.0%, while in the PCT group it was 18.2%. The DCR was 92% in the PCIT group and 93.4% in the PCT group. There were 16 (64.0%) patients in the PCIT group and 95 (69.3%) patients in the PCT group received no more than four cycles of preoperative treatment. Regardless of missing data (6 cases), TRAEs occurred in 71.6% of all included patients (116/162). Severe adverse events (SAEs), grade 3 or 4 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, occurred in 12.96% of all patients (21/162). The preoperative treatment regimens, TRAEs, response rates, and treatment cycles for the two groups are shown in Table 2.
Surgical and pathological characteristics
One patient (4.0%) underwent proximal gastrectomy (PG) in the PCIT group and nine patients (6.6%) underwent PG in the PCT group. Twelve (48%) patients in the PCIT group and 78 (56.9%) patients in the PCT group underwent total gastrectomy (TG). Twelve (48%) patients in the PCIT group and 50 (36.5%) patients in the PCT group received distal gastrectomy (DG). There was no significant difference in the range of gastrectomy between the two groups (p=0.595). All patients received D2 or D2+ lymphadenectomy with R0 resections. Combined resections were performed in 23 patients of all patients [1(4.0%) patient vs. 22(16.1%) patients; PCIT vs. PCT group; p=0.132)] because of infiltration of adjacent organs or gallbladder diseases, such as gallbladder stones or history of cholecystitis. Resected organs included the gallbladder, diaphragm, partial colon or mesentery, partial liver, spleen, partial pancreas, and ovary. Nine patients (36%) in the PCIT group underwent laparoscopic approaches (p=0.647), while in the PCT group, 56 patients (40.9%) underwent laparoscopic approaches. One patient (4%) in the PCIT group was converted to the open approach due to bleeding. Five patients (3.6%) in the PCT group converted to an open approach due to bleeding (two patients), tumor adhesion (two patients), and obesity (one patient). No statistically significant difference was found between the two groups in conversion to open approach (p=1.000). The proximal margin distance and distal margin distance of tumors were not significantly different between the two groups [median (IQR) proximal tumor margin distance was 4(2,6.88) cm in the PCIT group vs. 3(1.5,6.0) cm in the PCT group, p =0.287; median (IQR) distal tumor margin distance was 4.5(2,9.63) cm vs. 7(3.30,11.50) cm, p =0.096]. These two groups retrieved comparable numbers of lymph nodes (LNs), with the median (IQR) number of LNs per patient being 37 (37,46.5) in the PCIT group and 33.0 (27,44.5) in the PCT group. However, there were significantly more metastatic LNs in the PCT group than in the PCIT group [median (IQR) 2(0,8) vs. 2(0,3.5); p=0.014]. Neither the number of retrieved or metastatic LNs at each station was statistically different between the two groups (p=0.287 and p=0.096, respectively). Details are presented in Table 3.
Postoperative recovery parameters
There were no significant differences between the two groups in operation time (p=0.197), estimated blood loss (p=0.891), the first aerofluxus time (p=0.349), the first defecating time (p=0.800), the first time on liquid diets (p=0.233), and length of stay after surgery (p=0.278) (Table 4). All patients received IV-PCA after surgery. The duration of IV-PCA use was shorter in the PCIT group than in the PCT group, with a statistically significant difference [median (IQR), 72(72,84) hours vs. 72(72,96) hours; p=0.026]. During the hospital stay after surgery, both groups consumed the comparable amount of supplemental morphine (p=0.881) (Table 4). Neither group showed differences in postoperative pain at 24 hours, 48 hours, or 72 hours after surgery (p=0.375, p=0.601, and p=0.821, respectively) (Table 5).
Postoperative complications
Postoperative complication rate was 32.0% in the PCT group, and 31.4% in the PCIT group, with no significant difference between them (p=0.952). A total of ten severe complications occurred in the PCT group and none in the PCIT group, with no significant difference (p=0.302). There were two mortality cases (1.5%) in the PCT group and no cases in the PCIT group. No significant difference was found in perioperative mortality [0% (0/25) in the PCIT group vs. 1.5% (2/137) in the PCT group, p=1.00). Details are presented in Table 6.
Postoperative complication rate and perioperative mortality of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) based on subgroup analysis
In the PCIT group, the postoperative complication rate was 33.3% in the laparoscopic approach and 31.2% in the open approach, with no significant difference (p=1.000). These two approaches did not result in severe postoperative complications or perioperative deaths in the PCIT group (p=1.000). In the PCT group, the postoperative complication rate with the laparoscopic approach was 33.9% and 29.6% with the open approach. No significant difference was identified between the two approaches in the PCT group, either (p=0.594). The detailed results are listed in S1 Table and S2 Table.
Correlation analysis between age and postoperative complications
There was no significant difference in age between the complication group and in non-complication group [median (IQR) age of 63(54,69) years in the complication group vs. 63(52,68) years in non-complication group, p =0.536]. Besides, there was no correlation between the age and complication (correlation=0.160). Details are provided in S1 Table and S2 Table.