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World J Surg Oncol
World J Surg Oncol
World Journal of Surgical Oncology
1477-7819
BioMed Central London

39256787
3526
10.1186/s12957-024-03526-y
Research
Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching
LV Chen-Bin 1
Tong Lin-Yan 1
Zeng Wei-Ming 1
Chen Qiu-Xian 1
Fang Shun-Yong 1
Sun Yu-Qin 1
Cai Li-Sheng cailishengcls@163.com

2
1 grid.256112.3 0000 0004 1797 9307 Zhangzhou Affiliated Hospital of Fujian Medical University’sDepartment of Gastric Surgery, No.59 Sheng-li Road, Zhangzhou City, Fujian Province China
2 https://ror.org/050s6ns64 grid.256112.3 0000 0004 1797 9307 Department of Ultrasound, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou City, Fujian Province China
11 9 2024
11 9 2024
2024
22 24422 5 2024
1 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy.

Methods

We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival.

Results

After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease.

Conclusions

Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12957-024-03526-y.

Keywords

Neoadjuvant chemotherapy
Laparoscopic surgery
Hyperthermic intraperitoneal chemotherapy
Gastric cancer
PhD workstation at Zhangzhou Affiliated Hospital of Fujian Medical UniversityPDB202109 Startup Fund for Scientific Research at Fujian Medical University2018QH1214 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Gastric cancer is a prevalent type of cancer globally, with high rates of occurrence and death, ranking fifth and fourth in terms of malignant tumors, respectively [1]. Despite radical surgery being the primary and most efficient treatment for gastric cancer, approximately 70% of patients still experience recurrence and metastasis after surgery, particularly those with cT4 gastric cancer [2, 3]. Multiple research studies indicate that neoadjuvant chemotherapy has the potential to lower the likelihood of postoperative recurrence and metastasis and enhance the outlook for individuals diagnosed with advanced gastric cancer [4–6]. Nevertheless, the prognosis for patients with advanced gastric cancer remains poor, with the recurrence rate of peritoneal implantation metastasis after radical gastrectomy ranging from 35 to 50%, making it the primary mode of recurrence for gastric cancer [3, 7–9]. Hence, preventing peritoneal metastasis following radical gastrectomy is crucial.

HIPEC can successfully prevent peritoneal metastasis in gastric cancer patients by administering chemotherapy drugs directly into the abdomen and utilizing high temperatures to eliminate cancer cells. Several research studies indicate that HIPEC can be beneficial for reducing peritoneal metastasis and increasing the survival rate of individuals diagnosed with late-stage gastric cancer [10–13]. For cT4 gastric cancer patients, who have a high risk of postoperative recurrence and peritoneal metastasis, laparoscopic surgery after neoadjuvant chemotherapy allows patients to benefit from minimally invasive surgery while receiving standardized gastric cancer treatment. Combined with postoperative prophylactic HIPEC, this approach is expected to improve patient prognosis [11, 13].

In this research, we utilized propensity score matching to assess the effectiveness of neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy along with postoperative HIPEC for preventing cancer in individuals with cT4N + M0 gastric cancer by contrasting the recurrence rates, 3-year overall survival (OS), and disease-free survival (DFS) among the non-HIPEC and prophylactic HIPEC groups.

Methods

Patients

This study analyzed the medical records of 223 patients diagnosed with cT4N + M0 gastric cancer who underwent laparoscopic total gastrectomy following neoadjuvant chemotherapy at Zhangzhou Hospital, Fujian Medical University’s Department of Gastric Surgery, from June 2017 to December 2021.

The inclusion criteria were patients with advanced tumors who were staged as T4a-b, N+, or M0 on preoperative imaging; aged 18–75 years; pathologically diagnosed with gastric adenocarcinoma; provided informed consent; and underwent laparoscopic radical total gastrectomy and standardized D2 lymph node dissection. Exclusion criteria included preoperative or intraoperative identification of peritoneal and distant spread of cancer, incomplete resection, contraindications to HIPEC or systemic chemotherapy drugs, previous malignancies within the past 5 years, and the need for simultaneous surgery for other conditions. The 174 eligible patients were categorized into two groups based on whether postoperative HIPEC was conducted: a non-HIPEC group consisting of 142 patients and a HIPEC group consisting of 32 patients. To make the data of the two groups comparable, age, sex, and tumor stage were utilized as matching criteria, and the propensity score technique was employed to pair the two groups at a ratio of 1:2, with a caliper threshold of 0.2. A total of 80 patients were divided into two groups: 29 in the HIPEC group and 51 in the non-HIPEC group, as shown in Fig. 1.

Fig. 1 Study flowchart. HIPEC: hyperthermic intraperitoneal chemotherapy

This retrospective study was approved by the Ethics Committee of Zhangzhou Hospital Affiliated with Fujian Medical University. All patients underwent standard preoperative tests, such as CT scans of the chest and abdomen and tumor marker analysis; additional imaging, such as positron emission tomography (PET)-CT and bone scans, was performed as needed to check for distant spread of the cancer. The stage of gastric cancer was classified according to the 8th edition of the American Joint Committee on Cancer (AJCC) on Cancer Staging System [14].

Surgical methods and HIPEC procedure

An identical team of surgeons conducted every surgery, with each patient receiving laparoscopic radical total gastrectomy with D2 lymphadenectomy following the 2010 3rd edition of the Japanese Guidelines for Gastric Cancer Treatment [15]. The patient was positioned lying on their back with their legs apart, and a small tube was inserted below the belly button for observation; a larger tube was inserted 2 cm below the rib on the left side for the main procedure; and smaller tubes were inserted on the right side below the rib and above the belly button on both sides for additional procedures, with a pressure of 12 mmHg in the abdomen. The surgeon stood to the left of the patient, the assistant to the right, and a mirror holder was positioned between the patient’s legs. D2 lymph node dissection was carried out, with the specific steps of the dissection being documented in a previous publication [16]. Total gastrectomy was performed with esophagus-jejunum Roux-en-Y digestive tract reconstruction.

In the HIPEC group, approximately 3 weeks postsurgery, a 16-gauge needle guided by a color ultrasound was used to perform left upper and right lower abdominal punctures and catheterizations in the treatment room next to the bed. Hyperthermic perfusion and circulation were performed using a HIPEC machine (China, Model: HGGZ-102). The perfusion solution was consistently introduced and removed from the abdominal cavity at a steady temperature, rate, and quantity. The prophylactic HIPEC regimen consisted of 80 mg of docetaxel (60 min, 42 ± 1 °C). The perfusion fluid was a mixture of normal saline and docetaxel at a dose of 3000–5000 ml. The circulation flow rate was 300–500 ml/min, and a total of 1–3 courses were administered according to the patient’s tolerance, with an interval of 48 h between treatments. During the perfusion process, the patient was instructed to turn over appropriately from side to side to allow the drug to fully contact the peritoneum and enhance its therapeutic effect.

Perioperative chemotherapy scheme and cycle

All individuals were treated with neoadjuvant chemotherapy followed by postoperative adjuvant chemotherapy using the SOX (Oxaliplatin and S-1) or XELOX (Oxaliplatin and Capecitabine) regimen [17]. The patients received 2–4 cycles of chemotherapy before surgery and 4–6 cycles of chemotherapy after surgery. The HIPEC team began administering standard chemotherapy 48 h post-HIPEC, while the control group initiated their first chemotherapy treatment 3 to 4 weeks postsurgery.

Postoperative follow-up

Postoperative follow-ups were conducted by a dedicated person through outpatient visits, home visits and telephone calls. Follow-up assessments were performed every quarter for the first 2 years and then biannually for the following 3–5 years. The majority of patients received standard physical check-ups, blood tests (such as CA19-9 and CEA levels), chest X-rays, full abdominal ultrasounds or CT scans, and yearly gastroscopies. The OS time was recorded from the time of surgery to the last follow-up, death, or the time when the follow-up database was closed (such as loss to follow-up or death from other diseases). Disease-free survival (DFS) was determined from the date of the surgical procedure until the occurrence of tumor recurrence or mortality. Local recurrence or distant metastasis confirmed by imaging or pathology was considered tumor recurrence, and the site of recurrence was determined based on the earliest location of the finding.

Statistical analysis

Statistical analysis was performed using the R4.1.0 software packages “MatchIt” and “foreign” and SPSS 26.0 statistical software. The χ2 test was used for analyzing the categorical data; the measurement data are expressed as χ ± S. Categorical data were examined with either the χ2 test or Fisher’s exact test, whereas numerical data were assessed using the t test. Data that did not follow a normal distribution were examined with the Mann‒Whitney test. Survival rates were calculated with the Kaplan–Meier method, and the log-rank test was used to compare differences between the two groups. Statistical significance was set at P < 0.05.

Results

Comparison of clinicopathologic characteristics between the two groups before and after matching

The general clinicopathological characteristics of the entire group of patients are shown in Table 1. Prior to matching, the percentage of individuals with neurovascular invasion, tumor differentiation G2-3, diffuse type Lauren staging, ypT staging 3–4, ypN staging 2–3, and postoperative pathology of Stage II–III in the HIPEC cohort was notably greater than that in the non-HIPEC cohort. Following the matching process, there were no notable variations in the clinicopathological information of the patients within the two groups, as shown in Table 1. After matching there were no significant differences in postoperative complications and length of hospitalisation between the two groups as shown in supplementary Table 1.

Table 1 Characteristics of Patients in the HIPEC and NonHIPEC Groups before and after matching

	Overall cohort		After propensitymatching		
Characteristics	Non-HIPEC	HIPEC	P value		Non-HIPEC	HIPEC	P value	SMD	
	(n = 142)	(n = 32)			(n = 51)	(n = 29)			
Age, yrs			0.270				0.725	0.036	
< 65	78(54.9%)	21(65.6%)			30(58.8%)	19(65.5%)			
≥ 65	64(45.1%)	11(34.4%)			21(41.2%)	10(34.5%)			
Sex			0.683				0.746	0.034	
Male	107(75.4%)	23(71.9%)			37(72.5%)	22(75.9%)			
Female	35(25.6%)	9(28.1%)			14(27.5%)	7(24.1%)			
BMI, kg/m2	22.1 ± 3.2	22.3 ± 2.9	0.331		21.9 ± 3.1	22.2 ± 2.9	0.394	0.087	
ASA status			0.696				0.847	0.023	
1	70(49.3%)	17(53.1%)			27(52.9%)	16(55.2%)			
2	72(50.7%)	15(46.9%)			24(47.1%)	13(44.8%)			
Vascular invasion			< 0.001				0.286		
No	70(49.3%)	5(15.6%)			11(21.6%)	4(13.8%)			
Yes	72(50.7%)	27(84.3%)			40(78.4%)	25(86.2%)			
Perineural invasion			0.003				0.370		
No	51(35.9%)	1(3.1%)			6(11.8%)	1(3.4%)			
Yes	91(64.1%)	31(96.9%)			45(88.2%)	28(96.6%)			
Tumor size	52.4 ± 22.9	49.2 ± 21.5	0.076		54.9 ± 23.9	54.4 ± 22.1	0.860		
Extended resection			0.643				0.226		
No	120(84.5%)	27(84.3%)			41(80.4%)	25(86.2%)			
Yes	22(15.5%)	5(15.6%)			10(19.6%)	4(13.8%)			
Histopathological grade			0.013				0.070		
G1	4(2.8%)	0(0.0%)			1(2.0%)	0(0.0.%)			
G2	47(33.1%)	3(9.4%)			16(31.4%)	3(10.3%)			
G3	91(64.1%)	29(90.6%)			34(66.6%)	26(89.7%)			
Lauren subtype			0.003				0.255		
intestinal type	82(57.7%)	10(31.3%)			27(52.9%)	13(44.8%)			
diffuse type	35(24.6%)	14(43.7%)			15(29.4%)	10(34.5%)			
hybrid type	25(17.7%)	8(25.0%)			9(17.7%)	6(20.7%)			
Tumor location			0.421				0.554		
U	79(55.6%)	21(65.6%)			26(51.0%)	18(62.1%)			
M	53(37.3%)	6(18.8%)			16(31.4%)	6(20.7%)			
L	20(14.1%)	5(15.6%)			9(17.6%)	5(17.2%)			
cT category			0.839				0448		
4a	86(60.6%)	20(62.5%)			29(56.9%)	19(65.5%)			
4b	56(34.4%)	12(37.5%)			22(43.1%)	10(34.5%)			
ypT category			< 0.001				0.915	0.015	
T0	7(4.9%)	0(0.0.%)			0(0.0.%)	0(0.0.%)			
T1	12(8.5%)	0(0.0.%)			0(0.0.%)	0(0.0.%)			
T2	18(12.7%)	0(0.0.%)			0(0.0.%)	0(0.0.%)			
T3	35(24.6%)	1(3.1%)			2(3.9%)	1(3.4%)			
T4	70(49.3%)	31(96.9%)			49(96.1%)	28(96.6%)			
ypN category			0.003				0.689	0.046	
N0	51(35.9%)	4(12.5%)			5(9.8%)	4(13.8%)			
N1	35(24.6%)	8(25.0%)			15(29.4%)	8(27.6%)			
N2	24(16.9%)	3(9.4%)			10(19.6%)	3(10.3%)			
N3	32(22.5%)	17(53.1%)			21(41.2%)	14(28.3%)			
ypTNM stage			0.002				0.767		
0	7(4.9%)	0(0.0.%)			0(0.0.%)	0(0.0.%)			
I	21(14.8%)	1(3.1%)			1(2.0%)	1(3.4%)			
II	42(29.6%)	3(9.4%)			7(13.7%)	3(10.3%)			
III	72(50.7%)	28(87.5%)			43(84.3%)	25(86.3%)			

Comparison of postoperative recurrence between the two groups

The peritoneum was the most frequent location for recurrent metastasis in all patients, with distant organs, distant lymph nodes, localized regions, and bone metastases following a decreasing order of prevalence. In the prematched HIPEC group, the total percentage of patients who experienced recurrence was 34.4%, which was less than the percentage in the non-HIPEC group (45.8%), although the difference was not statistically significant. Patients in both groups had similar rates of local recurrence, peritoneal recurrence, and distant metastasis at all locations. The HIPEC group had notably lower recurrence rates at all sites (27.6% vs. 58.2%, P = 0.07) and in the lung (0.0% vs. 7.8%, P = 0.112) and peritoneum (6.9% vs. 25.5%, P = 0.041) than did the non-HIPEC group, as shown in Table 2.

Table 2 Comparison of postoperative recurrence and metastasis in the two groups

	Overall cohort		After propensitymatching		
Sites	Non-HIPEC	HIPEC	P value		Non-HIPEC	HIPEC	P value		
	(n = 142)	(n = 32)			(n = 51)	(n = 29)			
Local regions			0.892				0.915	
No	134(94.4%)	30(93.8%)			49(96.1%)	28(96.6%)		
Yes	8(5.6%)	2(6.2%)			2(3.9%)	1(3.4%)		
Peritoneum			0.540				0.041	
No	118(83.1%)	28(87.5%)			38(74.5%)	27(93.1%)		
Yes	24(16.9%)	4(12.5%)			13(25.5%)	2(6.9%)		
Liver			0.775				0.631	
No	136(95.8%)	31(96.9%)			48(94.1%)	28(96.6%)		
Yes	6(4.2%)	1(3.1%)			3(5.9%)	1(3.4%)		
Lung			0.237				0.122	
No	136(95.8%)	32(100.0%)			47(92.2%)	29(100.0%)		
Yes	6(4.2%)	0(0.0%)			4(7.8%)	0(0.0%)		
Other distal organs			0.912				0.682	
No	137(96.5%)	31(96.9%)			50(98.0%)	28(96.6%)		
Yes	5(3.5%)	1(3.1%)			1(2.0%)	1(3.4%)		
Bone			0.925				0.915	
No	138(97.2%)	31(96.9%)			49(96.1%)	28(96.6%)		
Yes	4(2.8%)	1(3.1%)			2(3.9%)	1(3.4%)		
Lymph node			0.679				0.640	
No	130(91.5%)	30(93.8%)			46(90.2%)	27(93.1%)		
Yes	12(8.5%)	2(6.2%)			5(9.8%)	2(6.9%)		
Total			0.240				0.07	
No	77(54.2%)	21(65.6%)			21(41.2%)	21(72.4%)		
Yes	65(45.8%)	11(34.4%)			30(58.2%)	8(27.6%)		
Abbreviations: HIPEC, hyperthermic intraperitoneal chemotherapy

Comparison of survival between the two groups

The duration of the follow-up was prolonged until December 2023, with a median follow-up period of 49 months (ranging from 15 to 78 months) for the entire cohort. Prior to comparison, the 3-year overall survival and disease-free survival rates of the HIPEC cohort were similar to those of the non-HIPEC cohort (Fig. 2A and B). According to the comparison, the 3-year overall survival rate for the HIPEC cohort was 63.2%, which was a notable increase compared to that of the non-HIPEC group (38.5%), despite the lack of statistical significance (P = 0.073; Fig. 3A). The three-year disease-free survival rate in the HIPEC cohort was significantly greater than that in the non-HIPEC cohort (59.0% vs. 35.2%, P = 0.033), as shown in Fig. 3B.

Fig. 2 Comparison of the overall and disease-free survival rates of patients in the HIPEC and non-HIPEC groups before matching: (A) 3-year overall survival outcomes and (B) 3-year disease-free survival outcomes. HIPEC: hyperthermic intraperitoneal chemotherapy; HIPEC(0): non-HIPEC group; HIPEC(1): HIPEC group

Fig. 3 Comparison of the overall and disease-free survival rates of patients in the HIPEC and non-HIPEC groups after matching: (A) 3-year overall survival outcomes of all patients, (B) 3-year disease-free survival outcomes of all patients, (C) 3-year overall survival outcomes of stage III patients and (D) 3-year disease-free survival outcomes of stage III patients. HIPEC: hyperthermic intraperitoneal chemotherapy; HIPEC(0): non-HIPEC group; HIPEC(1): HIPEC group

Comparison of survival between the two groups of stage III patients

After stratification by postoperative pathological stage and matching, compared with the non-HIPEC cohort, the HIPEC cohort exhibited superior 3-year OS (62.4% vs. 34.8%, P = 0.077) and DFS (47.4% vs. 20.4%, P = 0.022) (Fig. 3C and D).

Discussion

The general enhancement in the outlook for gastric cancer is not substantial. One of the main reasons for this is the high proportion of patients with advanced disease at the time of diagnosis. In China, the number of early gastric cancer cases is 20%, and locally advanced gastric cancer cases account for 70% [18]. Neoadjuvant chemotherapy has become increasingly common for treating locally advanced gastric cancer in recent years due to its ability to decrease tumor size and stage and enhance the rate of surgical resection, particularly for cT4 patients [4, 5]. Furthermore, advancements in laparoscopic tools and the enhanced skills of surgeons have led to increased interest in the use of neoadjuvant chemotherapy alongside radical gastrectomy for treating locally advanced gastric cancer [19]. Recent research indicates that laparoscopic D2 radical gastrectomy offers specific benefits in managing advanced gastric cancer [20]. Even with neoadjuvant chemotherapy, laparoscopic surgery is still considered safe and dependable compared to open surgery, with no significant impact on the occurrence or death rate of perioperative complications [21]. Despite the need for radical surgery, peritoneal metastasis remains the most common and earliest form of disease progression in patients with gastric cancer [3, 7, 8]. Approximately 50% of patients develop peritoneal metastasis after surgery, with an extremely poor prognosis [9]. The best combination of multimodal treatments, such as HIPEC in adjuvant therapy, is being explored to prevent peritoneal metastasis in gastric cancer patients.

The application of therapeutic HIPEC has been recognized in patients who have developed peritoneal metastasis [22]. Nevertheless, the effectiveness of preventive HIPEC in decreasing the incidence of peritoneal metastasis in gastric cancer patients with high-risk factors such as stage T4 disease is still under investigation. A meta-analysis involving 32 nonrandomized controlled trials (2520 patients) revealed that radical surgery with HIPEC was effective at reducing the risk of peritoneal metastasis (RR = 0.63, 95% CI 0.45–0.88; P < 0.01) [23]. An analysis of the clinical and pathological information of 132 patients with cT4 gastric cancer performed by Lee et al. [11] revealed that undergoing radical gastrectomy along with early postoperative prophylactic HIPEC could lower the occurrence of peritoneal metastasis, although it did not affect the rate of distant metastasis. A phase II clinical study conducted by Fan et al. [24] revealed that radical gastrectomy combined with cisplatin HIPEC did not reduce the recurrence rate of peritoneal metastasis. However, in most studies, HIPEC was performed under general anesthesia with thicker catheters placed during the operation, especially during or immediately after the operation, and only one treatment was performed, which may pose some risks [25]. Modified HIPEC treatment under bedside ultrasound guidance requires only local anesthesia and the use of thinner catheters, which is well tolerated, safe, and repetitive in patients [13]. In a study involving patients with stage III gastric cancer, researchers utilized bedside-adapted HIPEC and discovered that administering prophylactic HIPEC after surgery decreased the chances of ovarian (7.0% vs. 0.0%) and peritoneal metastasis (21.1% vs. 10.5%, P = 0.198). However, there was no significant difference in metastasis to other locations (such as the lung, bone, brain, liver, or abdominal lymph nodes) between the two groups. The research indicated that administering prophylactic HIPEC at the bedside after surgery notably decreased the occurrence of peritoneal recurrence in individuals with cT4 stomach cancer (6.9% vs. 25.5%, P = 0.041).

Nevertheless, the outcome for individuals with cT4 stomach cancer following prophylactic HIPEC surgery is still uncertain. Previous studies revealed that administering postoperative prophylactic HIPEC enhanced long-term survival outcomes for patients diagnosed with late-stage gastric cancer [10, 26]. According to a study by Allievi et al. [27], HIPEC increased the 1- and 3-year OS and DFS rates for patients with advanced gastric cancer at high risk of recurrence. A multicenter prospective clinical study indicated no difference in OS between the HIPEC and non-HIPEC groups, while DFS was significantly better in the HIPEC group [28]. On the other hand, Diniz and colleagues [29] reported that HIPEC treatment did not improve patient prognosis. A real-world retrospective study from China also showed no survival benefit for gastric cancer patients who underwent HIPEC (P = 0.220 for OS and P = 0.370 for cancer-specific survival) [30]. In this study only the 3-year DFS rates in the HIPEC group were significantly greater than those in the non-HIPEC group. While the 3-year OS rates has an increasing trend in the HIPEC group although there is no statistical difference. HIPEC significantly enhanced the 3-year overall survival (62.4% vs. 34.8%, P = 0.077) and disease-free survival (47.4% vs. 20.4%, P = 0.022) rates, especially in patients with stage III cancer following neoadjuvant chemotherapy. Liu et al. [13]. also showed that the middle DFS (29 compared to 15 months, P = 0.006) and OS (42 compared to 31 months, P = 0.042) in the HIPEC category were notably greater than those in the non-HIPEC category. Hence, effective treatments for advanced-stage T4 gastric cancer require a combination of therapies and ongoing optimization.

There were certain limitations in this research. This was a single-center retrospective study, which may have led to bias. Hence, we employed propensity score matching to reduce selection bias, enhancing comparability between the two groups and increasing the accuracy of the results. Second, the sample size was small, and the impact of biomarkers such as HER2 and CPS on the prognosis of patients is not clear. In additionthe lack of multivariate analysis in OS and DFS is also a deficiency of this study. Therefore, the long-term oncologic outcomes of neoadjuvant chemotherapy combined with laparoscopic radical gastrectomy and postoperative preventive HIPEC need to be confirmed in large-sample, multicenter, randomized controlled studies.

In conclusion, our study suggested that postoperative prophylactic HIPEC can reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and improve the prognosis of such patients.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Acknowledgements

We express gratitude to the individuals who contributed significantly to this research, such as nurses, pathologists, postgraduate physicians, data analysts, peer reviewers, and editorial staff. They did not receive any financial compensation for the work they did.

Author contributions

Chen-Bin Lv, Lin-yan Tong, and Wei-Ming Zeng conceived the study, analyzed the data, and drafted the manuscript. Li-Sheng Cai helped critically revise the manuscript for important intellectual content. Qiu-Xian Chen, Shun-Yong Fang, and Yu-Qin Sun helped collect the data and design the study. All the authors have reviewed and approved the final manuscript.

Funding

Funding for this research was provided by the Startup Fund for Scientific Research at Fujian Medical University (2018QH1214) and the Climbing Fund for PhD Workstation at Zhangzhou Affiliated Hospital of Fujian Medical University (PDB202109).

Data availability

The dataset analyzed for this study is available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Zhangzhou Hospital Affiliated to Fujian Medical University (No. 2024KYB068). Informed consent was obtained from all subjects and/or their legal guardian(s). All procedures were undertaken in accordance with the Helsinki Declaration and all methods were carried out in accordance with relevant guidelines and regulations in the declaration.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

cT stage Clinical T stage

HIPEC Hyperthermic intraperitoneal chemotherapy

ypN stage Pathological N stage after neoadjuvant chemotherapy

CT Computed Tomography

PET Positron Emission Tomography

AJCC American Joint Committee on Cancer

DFS Disease-Free Survival

OS Overall Survival

BMI Body Mass Index

ASA American society of anesthesiologists physical status classification

SOX Oxaliplatin and S-1.

XELOX Oxaliplatin and Capecitabine.

SMD Standardized mean difference

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Chen-Bin Lv, Lin-Yan Tong and Wei-Ming Zeng contributed equally to this work and should be considered co-first authors.
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