Hyperthermic intraperitoneal chemotherapy for preventing and treating peritoneal metastasis in gastric cancer

Abstract

Peritoneal metastasis is one of the most frequent types of metastasis associated with poor prognosis in cases of gastric cancer. One new method for treating the disease, known as hyperthermic intraperitoneal chemotherapy (HIPEC), involves local delivery of heat-activated chemotherapy drugs in order to target free circulating tumor cells and micrometastatic lesions. The purpose of this minireview paper is to describe recent developments in the field of HIPEC as a means of preventing and managing peritoneal dissemination in patients with gastric cancer. Studies conducted have shown the effectiveness of HIPEC in decreasing the risk of peritoneal recurrences and improving the prognosis of survival. Although certain difficulties remain in terms of surgical and postoperative complications, efforts to improve the effectiveness of the treatment are underway.

Key Words: Hyperthermic intraperitoneal chemotherapy; Gastric cancer; Peritoneal metastasis; Cytoreductive surgery; Pressurized intraperitoneal aerosol chemotherapy

Core Tip: Hyperthermic intraperitoneal chemotherapy relies on a synergic use of heat and chemotherapy to prevent and manage the metastatic disease of the stomach. Hyperthermic intraperitoneal chemotherapy can improve patient outcomes in terms of prevention of peritoneal metastases and survival, especially when used along with cytoreductive surgery. While complications may arise during the perioperative period, such issues can be managed in dedicated settings.

INTRODUCTION

Gastric cancer is one of the serious diseases in the world and accounts for the fifth most common cancer diagnosis and the fourth most common cause of death from cancers all over the world[1]. There has been tremendous progress made in the field of gastric cancer surgery and systemic treatment such as laparoscopic radical gastrectomy, D2 lymphadenectomy, and others, yet the outlook on patients with advanced stage cancer is quite grim and is marked by poor survival rate of only five years after cancer diagnosis. Peritoneal metastases are especially important since they form the most common metastasis type in gastric cancer[2]. Epidemiological data show that approximately 15%-30% of patients diagnosed with gastric cancer will have peritoneal metastasis[3,4]. Traditional systemic intravenous chemotherapy has limited effectiveness in the treatment of peritoneal metastasis in gastric cancer, mainly due to the plasma-peritoneal barrier: Only a small portion of chemotherapy drugs can cross the plasma-peritoneal barrier to enter the peritoneal cavity during conventional chemotherapy, and chemotherapy drugs cannot reach an effective concentration in the peritoneum, resulting in poor treatment efficacy[5]. Once peritoneal metastasis occurs, the median survival time of patients is only 4-12 months[6]. Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a promising adjuvant therapy with favorable outcomes in managing peritoneal metastases from various malignancies. Typically administered following cytoreductive surgery (CRS), it involves the continuous circulation of chemotherapy agents heated to a specific temperature (typically 41-43 °C) within the peritoneal cavity. This modality leverages the synergistic effect of hyperthermia and chemotherapy to eradicate free-floating cancer cells and micrometastases[7]. Its advantage is that HIPEC achieves high concentration distribution of drugs in the peritoneal cavity through local administration, and at the same time utilizes the synergistic sensitization effect of thermotherapy, providing a new treatment option for the prevention and treatment of peritoneal metastases of gastric cancer[8]. As an important method of perioperative chemotherapy, HIPEC is gradually being recognized for its role in preventing peritoneal metastases of advanced gastric cancer[9]. Therefore, in-depth exploration of the application value of HIPEC in the prevention and treatment of peritoneal metastases of gastric cancer has important clinical significance and research prospects.

PATHOPHYSIOLOGICAL BASIS OF PERITONEAL METASTASIS OF GASTRIC CANCER

Mechanism of peritoneal metastasis

Peritoneal metastasis in gastric cancer is a multistep, multifactorial cascade. The important sequential process involves: (1) Disengagement and dissemination: Cancer cells from primary tumors detach and invade the stomach wall, pass through the serosa, and slough off into the peritoneal cavity; (2) Survive and migrate: Cancer cells survive in the peritoneal fluid, thriving in the distinct microenvironment with low oxygen, acidity, and lack of nutrients; (3) Adhere: Cancer cells stick to the peritoneum’s mesothelial cells; (4) Invasive and colonize: After adhering, they invade through mesothelial cells and their basement membrane and colonize the submesothelial area; and (5) Grow and develop blood supply: Colonized cells subsequently grow and develop blood vessels, leading to the growth of metastatic tumors. Several studies have revealed that the peritoneal environment is significantly effective in controlling metastatic lesion formation. When tumor cells infiltrate the peritoneal cavity, neighboring cells such as mesothelial cells, fibroblast cells, inflammatory cells, and macrophages produce matrix metalloproteinases, resulting in extracellular matrix degradation. Moreover, the urokinase-type fibrinogen activator causes matrix degradation and impairs the permeability barrier by activating pro-matrix metalloproteinases[10].

Analysis of factors affecting peritoneal metastasis

There are various factors that are involved in the occurrence of peritoneal metastasis. The tumor-node-metastasis classification of the tumor becomes important in which, if the tumor reaches the subserosa stage (T3) or reaches the serosa stage (T4), then there is a high possibility of free cancer cells detaching[11]. Histological type is another risk factor; diffuse or signet ring cell carcinomas tend to have a higher peritoneal seeding propensity due to a diffuse infiltrative growth pattern and weak intercellular adhesion[12]. In addition, peritoneal lavage fluid cytology (CY) status is an independent prognostic indicator; CY1 positivity indicates the presence of micrometastases in the peritoneal cavity, and even without gross nodules, the prognosis is significantly worse than that of CY0 patients. Preoperative or intraoperative detection of peritoneal gross metastasis is a clear marker of disease progression[13].

BASIC PRINCIPLES OF HIPEC

Working mechanism of HIPEC

The antitumor effect of HIPEC mainly stems from the synergistic effect of thermal effect and chemotherapeutic drugs. Its core mechanism includes three aspects: Directly killing tumor cells, enhancing drug efficacy, and regulating the tumor microenvironment. First, the continuously flowing infusion solution exerts a mechansurgical scrubbing effect on intraperitoneal implants and circulating tumor cells within the abdominal cavity. In addition, high intraperitoneal levels of anticancer drugs can be directed to eliminate free-floating cancer cells and remaining microscopic lesions. During HIPEC, normal tissue cells can tolerate temperatures up to 47 °C for one hour, whereas malignant cells begin to undergo irreversible damage at temperatures above 43 °C within the same period. HIPEC can maintain intraperitoneal temperatures of 43.0 ± 0.2 °C for over an hour, causing irreducible destruction to cancer cells while simultaneously minimizing injury of normal cells[14]. Besides, high temperature enhances the transmissibility of the cancer cell membrane and tumor blood vessels, increases the transmission and the absorption of therapeutic agents, amplifies the drug sensitivity, and also reduces chemotherapy-related adverse reactions[15,16]. Under conditions of high temperature, the effect of some drugs is magnified, and the depth of chemotherapy drug penetration is increased from around 1-5 mm. This significantly reinforces the interaction between high temperature and chemotherapy[17]. These combination of effects can contribute to the effectiveness of HIPEC in the treatment of peritoneal metastases.

Comparative advantages of HIPEC compared with traditional chemotherapy methods

HIPEC has unique pharmacological and clinical advantages over conventional systemic chemotherapy. Through the administration of high doses of cytotoxic drugs into the abdominal cavity, it guarantees strong local toxicity to both circulating and infiltrating tumor cells. The loco-regional technique, in conjunction with hyperthermia, circumvents the “plasma-peritoneal barrier”, which is one of the drawbacks of intravenous chemotherapy. As a result, HIPEC provides an exponential increase in drug concentration at the site of pathology with minimal systemic distribution of the medication, thus drastically reducing systemic side effects. The rationale behind the success of the therapeutic procedure of HIPEC is based on its dual mechanism; it not only permits the delivery and circulation of high doses of chemotherapy drugs in the abdominal cavity but also helps in increasing the uptake and diffusion of the chemotherapeutic agents into the tumor tissue by applying heat. Heat also makes cancer cells more sensitive to the cytotoxic drugs, thereby creating a synergy effect that enhances overall tumor cell killing. It is important to note that HIPEC is an intraoperative therapy, which is administered after CRS. This strategy makes it possible for the heated chemotherapy to act immediately on the newly uncovered surfaces of the peritoneum, even before any minute deposits are formed. The immediacy of the intervention process is vital in ensuring that the cancer cells that have been removed do not find their way back onto the surface of the peritoneum[18,19].

APPLICATION OF HIPEC IN THE PREVENTION OF PERITONEAL METASTASIS OF GASTRIC CANCER

Theoretical basis for the prevention of HIPEC

The theoretical basis for preventive HIPEC is mainly based on the “seed-soil” theory of peritoneal metastasis of gastric cancer. This theory holds that detached gastric cancer cells (seeds) need a suitable peritoneal microenvironment (soil) to colonize and grow[20]. HIPEC exerts its preventive effect by simultaneously targeting both the “seeds” and the “soil”. Surgical procedures may cause tumor cells to detach, forming free cancer cells in the peritoneal cavity. The hyperthermic chemotherapy solution directly lyses these free-floating “seeds”. More importantly, hyperthermia itself can induce changes in the peritoneal “soil”, such as altering the expression of adhesion molecules on mesothelial cells and reducing the secretion of pro-metastatic cytokines, thereby making the microenvironment less hospitable for implantation[21]. Clinical studies have confirmed that this preventive intervention can greatly improve the prognosis of high-risk patients, and not only reduce the overall recurrence rate and the peritoneal-specific recurrence rate after surgery but also effectively prolong the 1-year, 3-year, and 5-year survival rates of patients and provide essential guarantees for a prognosis among gastric cancer patients with a high risk of metastasis[22].

Clinical research evidence and case analysis

In recent years, a number of high-quality clinical studies have confirmed the effectiveness of preventive HIPEC. A recently published study on the use of preventive HIPEC in highly-risk gastric cancer patients demonstrated not only improved outcomes during the perioperative period but also enhanced survivals. This suggests that integrating preventive HIPEC may help reduce peritoneal recurrence compared to traditional adjuvant therapy[23]. In the comprehensive systematic review, the peritoneal recurrence rate in the HIPEC cohort was significantly lower; it seems probable that preventive HIPEC may play a positive role in inhibiting the spread of tumor cells to the peritoneum[24]. In the same vein, a study in a randomized cohort with locally advanced gastric cancer demonstrated that the group receiving HIPEC combined with D2 gastrectomy achieved superior short-term postsurgical outcomes, notably higher disease-free survival rates, and lower rates of recurrence in the peritoneum compared to the group undergoing surgery alone[25].

Current controversies and challenges

Although HIPEC as prophylaxis in high-risk GC patients has distinct merits, controversies exist in terms of the survival advantage gained vs the major risk involved. One of the key controversies lies in the relatively high morbidity that comes along with CRS + HIPEC treatments. It is noted, for example, that patients under HIPEC as prophylaxis suffer prolonged time in rehabilitation, delaying their return to normal functioning, thus lowering patient satisfaction with the results of the surgery[26]. This is aggravated by complications arising after surgery. In a recent study conducted by Valencia-Sola et al[27] in 2025, it was reported that the total number of postoperative complications experienced by patients undergoing CRS + HIPEC for peritoneal surface malignancies was as high as 62.3%, with infections being the most common complication at 23.4%. Factors contributing to the risk included surgery duration, which correlated with renal failures and infections, as well as the need for organ support therapy after surgery. Apart from procedural morbidity, the side effects due to chemotherapy as well as systemic problems are a matter of concern regarding HIPEC therapy. In terms of hematologic toxicities, neutropenia and thrombocytopenia are known issues, especially in the elderly patients, and there is a risk of nephrotoxicity caused by the chemotherapeutic drugs resulting in kidney and liver dysfunction[28]. Nevertheless, another significant aspect comes into play when evaluating the risks and benefits associated with HIPEC procedure. As the above mentioned 2025 study revealed, despite a high proportion of adverse effects among their subjects, there was no association between their presence and 1-year or overall mortality rates[27]. This finding implies that with a proper management strategy in specialized clinics, such complications can be addressed without affecting patient survival from the aggressive treatment. Moreover, another question that arises is whether it is possible to apply HIPEC procedure to high-risk patients with gastric cancer. Since different institutions do not encounter similar issues in identical ways, access to prophylactic HIPEC may be heterogeneous, and this will certainly affect how patient selection and management will take place, based on their different demographics[29]. The variability of knowledge and capability contributes to the risk-benefit calculation because results vary according to centers. In summary, the ongoing debate is not only whether HIPEC causes morbidity, but also how best to choose patients and optimize perioperative care for HIPEC to enhance survival benefit without compromising patient safety.

APPLICATION OF HIPEC IN THE TREATMENT OF PERITONEAL METASTASES OF GASTRIC CANCER

Operational procedures and key technical points in treating HIPEC

The standard treatment method for peritoneal metastasis due to gastric cancer follows a thorough two-step protocol, CRS and HIPEC. The first step is concerned with the removal of macroscopic tumor nodules via thorough and sometimes very aggressive peritoneal stripping, along with visceral resections when needed. The main idea here is to conduct cytoreduction to the extent where there is no visible residual tumor left behind (CC-0). It goes without saying that the success of this cytoreduction procedure becomes an important prognosis factor for patients. The second step, HIPEC, occurs intraoperatively. It consists of perfusing hot anticancerous agents within the abdomen over a pre-specified time frame. HIPEC’s main purpose is to destroy any residual microscopic tumors left over after surgical intervention. The effectiveness of HIPEC depends heavily on various procedural aspects of the process. The choice of the right chemotherapeutic agent is key. Drugs like mitomycin C, cisplatin, or oxaliplatin may be selected for their known effectiveness and their synergy with heat. The time period of chemoperfusion, normally between 60 to 90 minutes, should ensure sufficient contact between the drugs and tissue. Additionally, the dosage of the chemotherapeutic drug in the perfusion fluid, as well as its heating to maintain hyperthermia at a temperature of 41-43 °C, are carefully controlled. The overall aim is to attain a delicate balance: To achieve optimal drug penetration within any remaining tumor mass, while ensuring minimal systemic drug exposure and associated toxicity[8].

Efficacy assessment indicators and methods

In assessing the therapeutic efficacy of HIPEC, a multi-dimensional system has been established. The major indices include progression-free survival, overall survival, and changes in the peritoneal cancer index (PCI). Progression-free survival and overall survival are two critical survival variables that can be analyzed by the Kaplan-Meier method and log-rank test, with the ability to reflect improvements in disease progression and enhancement of patient survival due to the treatment. The PCI should be measured by laparoscopic exploration or imaging studies, such as enhanced computed tomography and magnetic resonance imaging, with inclusion of the burden of metastatic lesions accurately, acting as the main criterion for verifying whether the micrometastases have been effectively eradicated by the treatment. Moreover, much attention is paid to quality of life in patients after surgery. Furthermore, patient-reported quality of life is a critical secondary endpoint. Most contemporary studies employ standardized instruments such as the Short Form Health Survey (SF-36) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) to comprehensively evaluate the impact of treatment across multiple domains, including physical function, symptom burden (e.g., pain), and emotional well-being.

Latest clinical trial results

Several well-designed clinical trials have, in fact, established that the addition of HIPEC to a treatment regimen confers significant and clinically meaningful overall survival benefit for gastric cancer patients with peritoneal metastases. Khomiak et al[30] showed that those who were treated with CRS in combination with HIPEC in rigorously screened patients with gastric cancer with peritoneal metastases had a significantly prolonged median overall survival (18.1 months to 9.3 months) and a 43% reduction in the risk of death, CRS and HIPEC in the right population can significantly improve overall survival. Lin treated 30 gastric cancer patients with intraoperatively detected limited peritoneal metastases (PCI ≤ 12) using laparoscopic CRS followed by HIPEC, achieving a median overall survival of 27 months, demonstrating that this minimally invasive combined approach is safe and effective, particularly for those with low peritoneal burden (PCI ≤ 6)[31]. These findings are particularly important in the fact that they confirm the notion that CRS with HIPEC is not simply palliative in nature but is rather a potentially curative-intent strategy offering a clear pathway to long-term survival for a well-defined population of individuals presenting with a limited peritoneal metastatic disease burden. Data from both Khomiak et al[30] and Lin et al[31] put together further strengthen the role of CRS + HIPEC in selected patients and alter the therapeutic paradigm for gastric cancer peritoneal metastases (Table 1).

Table 1 Results of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer peritoneal metastasis.

Ref.	Study design	Intervention	Median overall survival (month)	Key findings
Khomiak et al[30], 2024	Retrospective study	CRS + HIPEC	18.1:9.3	CRS + HIPEC was associated with significantly improved OS in a selected population
Lin et al[31], 2024	Clinical trial	CRS + HIPEC + systemic chemotherapy	27	L-CRS followed by HIPEC is safe and feasible, offering potential survival benefits for limited peritoneal metastasis

The median overall survival data presented are derived from studies with distinct designs and patient selection criteria. Khomiak et al[30] (retrospective study) compared cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) vs systemic chemotherapy alone, while Lin et al[31] (prospective phase II trial) assessed local CRS combined with HIPEC and systemic chemotherapy in a selected cohort with limited peritoneal disease. The survival differences may reflect variations in treatment intensity, patient selection, and study design. Both studies support the potential role of CRS + HIPEC in selected patients, although generalizability may be influenced by selection bias and heterogeneity across studies. CRS: Cytoreductive surgery; HIPEC: Hyperthermic intraperitoneal chemotherapy; L-CRS: Local cytoreductive surgery.

SAFETY AND SIDE EFFECT MANAGEMENT OF HIPEC

Common complications and their management strategies

The complications related to HIPEC may roughly be divided into surgery-related and chemotherapy-related. Their occurrence is closely related to the scope of CRS resection, the perfusion time of HIPEC, and the individual conditions of patients, such as age and underlying diseases. Surgery-related complications include intestinal obstruction, anastomotic leakage, intraoperative and postoperative bleeding, and abdominal infection, which are often related to surgical trauma, tissue adhesion in the abdominal cavity, or improper aseptic technique. The main chemotherapy-related complications include myelosuppression, nephrotoxicity-particularly with cisplatin as the perfusion drug-and chemical peritonitis, which is mainly caused by the local stimulation and systemic absorption effect of chemotherapy drugs. The core of the management strategy for complications is “prevention first + multidisciplinary collaboration”. During the perioperation period, strict bowel preparation and standardized aseptic operations are performed to reduce the risk of infection. Liver and kidney functions should be assessed before operation, with adjustment of the dosage of drugs to reduce toxicity. In treatment, vital signs, electrolytes, and body temperature are monitored, and adequate hydration is maintained to keep the internal environment stable. Once complications occur, it is necessary to form a multidisciplinary team composed of surgery, oncology, and emergency medicine to develop an individualized plan and intervene in time to improve the prognosis of patients.

Safety evaluation and patient quality of life

While the risk of complications after CRS combined with HIPEC is an important consideration, contemporary clinical data suggests that these risks are manageable in experienced centers. A systematic analysis of outcomes indicates that about one-quarter of patients receiving this combined treatment regimen experience major postoperative complications. Specifically, the rate of combined anastomotic leakage-a serious surgical challenge-has been reported at 22% in certain cohorts, reflecting the complexity of the procedures involved[32]. Furthermore, data from another significant study provides more detail related to the severity of these complications and reports that the incidence of grade III-IV postoperative complications was comparatively low at only 15%[33]. This figure is important as it highlights that the vast majority of patients do not experience the most debilitating postoperative events. Regarding the all-important aspect of patient-reported outcomes, research into quality of life provides reassuring findings. Studies that have prospectively followed patients show that quality of life scores following HIPEC treatment were not significantly different from those observed in patients who underwent surgery alone. Importantly, some research suggests that HIPEC can lead to a meaningful improvement in cancer-related symptoms such as abdominal pain and bloating, particularly by controlling malignant ascites, thereby ultimately contributing to an enhanced quality of life for patients[24]. Another study shows that although patients experience significant declines in overall health and physical function shortly after undergoing CRS or HIPEC surgeries, most of these indicators return to baseline levels by 12 months after the surgery, and their quality of life also improves[34]. This suggests that while the often-arduous recovery journey may be challenging, those patients that receive the combined procedure are generally able to achieve similar quality of life to their surgical counterparts within the medium term.

FUTURE DEVELOPMENT DIRECTIONS AND CHALLENGES

Technological improvement directions

The development trend of HIPEC in technological innovation is minimally invasive and precision treatment. For instance, HIPEC can be supplemented with laparoscopic surgery. It has been shown in studies that not only does laparoscopic surgery shorten the recovery time, but it also reduces postoperative complications[35]. Pressurized intraperitoneal aerosol chemotherapy is a new form of intraperitoneal drug delivery. Low-dose chemotherapy is applied as a pressurized aerosol and suitable for patients with primary or secondary peritoneal cancer. It can be used as a supplement or alternative to HIPEC and is suitable for patients who cannot qualify for CRS/HIPEC and are intolerant or have developed systemic chemotherapy intolerance[36]. Meanwhile, a treatment plan that involves prophylactic HIPEC requires careful selection of patients, usually combining advanced imaging technologies with biomarkers, and stratifying patients according to their risk characteristics. These precision medicine methods are essential for maximizing the therapeutic effect of HIPEC and can reduce adverse reactions that may result from this intensified treatment[24].

In the future, drug research will not only be limited to traditional chemotherapy drugs. The application of targeted therapies, including anti-HER2 drugs and anti-angiogenic drugs in HIPEC and immune checkpoint inhibitors like programmed death 1/programmed death-ligand 1 inhibitors, is a cutting-edge research area. Meanwhile, robot-aided surgery, enhanced reality guidance systems, and real-time molecular imaging during HIPEC delivery can enhance surgical precision and further reduce complications. Furthermore, personalized medicine, especially through genomic analysis and targeted therapy, has a revolutionary potential to enhance the effectiveness of preventive HIPEC in populations at high risk (Table 2).

Table 2 Technological improvements in hyperthermic intraperitoneal chemotherapy for gastric cancer.

Specific technology/approach	Advantages	Challenges
Laparoscopic HIPEC	Reduces recovery time and postoperative complications	Proven safe and effective in selected patients; requires specialized training
PIPAC	Suitable for patients ineligible for CRS/HIPEC; low-dose localized delivery	Emerging alternative; role as supplement or alternative to HIPEC under study
Imaging + biomarkers + risk stratification	Maximizes therapeutic effect, reduces adverse reactions	Integrating multiple modalities for personalized pathways
Anti-HER2, anti-angiogenic drugs, programmed death 1/programmed death-ligand 1 inhibitors	Enhances synergy with HIPEC; potential for systemic and local control	Cutting-edge research area; optimal combinations and timing under investigation
Robot-assisted surgery, AR guidance, real-time molecular imaging	Improves surgical precision, reduces complications	Technologically advanced but cost and accessibility barriers
Genomic analysis + targeted therapy	Revolutionary potential for high-risk populations	Requires robust biomarkers and clinical validation

Listed technologies represent active innovations in hyperthermic intraperitoneal chemotherapy. Clinical integration depends on further research, technical maturation, and multidisciplinary collaboration. CRS: Cytoreductive surgery; HIPEC: Hyperthermic intraperitoneal chemotherapy; PIPAC: Pressurized intraperitoneal aerosolized chemotherapy; AR: Augmented reality.

CONCLUSION

In all, HIPEC shows an attractive benefit in the prevention and treatment of peritoneal metastasis from gastric cancer by using the synergistic effect of thermal effects and chemotherapy drugs as a locoregional treatment approach. Prophylactic HIPEC can decrease the occurrence of postoperative peritoneal metastasis in high-risk patients, while therapeutic HIPEC combined with systemic chemotherapy can prolong the survival of unresectable patients and improve disease-free survival. In the future, it will be necessary to conduct large-scale randomized controlled trials to further elucidate the optimal indication and regimen. It is also necessary to actively explore combined strategies with systemic therapy, targeted therapy, and immunotherapy. For instance, research based on the mathematical and inherited basis of gastric cancer may well direct the discovery of targeted therapies that will supplement HIPEC regimens, personalized medicine approaches, and treatment adjustments based on individual characteristics of the cancer; it is expected that this will be done in order to further improve the efficacy of HIPEC. Biomarkers and genetic analysis help predict treatment response and optimize the selected regimen; this can improve the global rate of survival and quality of life for patients at high risk for gastric cancer, for which tools such as liquid biopsy and organoid models are needed to get closer to precision and personalized treatment. Despite remaining challenges with regard to safety, standardization, and health economics, HIPEC undoubtedly offers a gleam of hope to overcome the intractable challenge of peritoneal metastasis in gastric cancer, and its development in the future will surely further reshape the treatment landscape for gastric cancer.