Gastric cancer with peritoneal metastases (GC-PM) carries a poor prognosis and estimated survival is less than 6 to 12 months. One potential treatment of GC-PM is cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Success of this treatment largely relies on tumor biology and patient selection. These operations carry a high risk of morbidity and mortality and their efficacy in GC-PM remains controversial. This study will review the updated literature for CRS ± HIPEC in patients with GC-PM.

The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer.

Patients with gastric cancer and synchronous metastases between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Patients were categorized based on the site of metastases. Median overall survival (OS) was calculated for each metastatic site group. Multivariable Cox regression analyses were performed to evaluate the association between patient, tumour, and treatment characteristics, including the impact of systemic therapy, on OS.

A total of 4072 patients were included, of whom 1835 (45.1%) had peritoneal metastases. Of these, 58.1% had isolated peritoneal metastases. For patients with metastatic gastric cancer treated with systemic therapy, the median OS was 9.0 months (95% confidence interval (CI): 8.6-9.5), compared to 1.7 months (95% CI: 1.7-1.9) for treatment-naïve patients, who received only palliative care. The survival for patients with isolated peritoneal metastases (4.4 months, 95% CI: 4.0-4.8 months) was similar to those with isolated non-peritoneal metastases (4.6 months, 95% CI: 4.2-5.1 months, adjusted HR: 0.94, 95% CI: 0.86-1.03, p = 0.185). Systemic therapy was associated with comparable survival in patients with peritoneal metastases and those with metastases at other sites.

This study demonstrates that there is no statistically significant difference in survival between patients with isolated peritoneal metastases and those with isolated non-peritoneal metastases in gastric cancer. Our findings emphasize the unique prognostic landscape for peritoneal metastases in gastric cancer, underscoring the need for disease-specific evaluations, rather than relying on assumptions derived from other cancer types.

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Gastric cancer (GC) commonly presents in advanced stages with metastatic spread to the peritoneal cavity, and outcomes associated with gastric cancer with peritoneal metastasis (GCPM) continue to carry a dismal prognosis. Persistent challenges in the detection of peritoneal metastasis (PM) have resulted in a relative paucity of high-quality data to inform management decisions. Several consensus groups have published recommendations to guide management, including most recently the National Comprehensive Cancer Network guidelines, which now include cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a potential treatment modality in select patients with GCPM. Multiple clinical trials have investigated the use of CRS/HIPEC and other peritoneal-directed therapies, such as intraperitoneal chemotherapy (IPC) and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). As high-volume centers work to incorporate such therapies into their practice, ongoing clinical trials are aimed at understanding their efficacy. Recent findings have improved understanding of the mechanisms and pathophysiology underlying GCPM while the discovery of novel targets offers potential for drug development and therapeutic strategies to overcome treatment resistance. This review highlights recent advancements and addresses the persistent challenges in managing GCPM while also offering a comprehensive summary of current guidelines and treatment strategies.

Palliative chemotherapy is the current standard among advanced gastric cancer (GC) patients with peritoneal metastasis (PM), while the role of gastrectomy with cytoreductive surgery and HIPEC remains unclear. The current study aimed to assess treatment outcomes among GC patients with PM undergoing gastrectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) using multinational cancer registries.

The analysis (2012-2022) included stage IV GC patients with PM undergoing gastrectomy and HIPEC from the European GASTRODATA Registry (EU cohort) and the American National Cancer Database (NCDB, U.S. cohort). The study outcomes were textbook oncological outcome (TOO) assessment and overall survival (OS).

Among 193 patients, 49.7 ​% were from the EU cohort and 50.3 ​% from the U.S.

EU cohort had significantly higher rates of pT4 tumors (EU: 50 ​% vs U.S.: 40.2 ​%), metastatic lymph nodes (EU: 68.8 ​% vs U.S.: 54.6 ​%), and ≥16 lymph nodes evaluated (EU: 91.7 ​% vs U.S.: 68 ​%). Postoperatively, the EU cohort had longer hospital stay (EU: 53.1 ​% vs 22.2 ​%, p ​< ​0.001), with no significant differences in 30-day readmission (EU: 14.6 ​% vs U.S: 7.2 ​%, p ​= ​0.11) and 90-day mortality (EU: 4.2 ​% vs U.S.: 9.3 ​%, p ​= ​0.25). TOO rates were 30.2 ​% and 32 ​% for EU and U.S. cohorts, respectively. Within the U.S. cohort, TOO achievement was associated with improved 1- (86.7 ​% vs. 57.4 ​%), 3- (55.8 ​% vs. 29.7 ​%), and 5-year OS (50.2 ​% vs. 29.7 ​%) (p ​= ​0.0025) survival compared with non-TOO.

Among patients with GC and PM undergoing gastrectomy and HIPEC, achievement of TOO was associated with decreased risk of postoperative complications (EU cohort) and improved long-term survival (U.S. cohort).

Patients with gastric cancer peritoneal metastases (GCPM) have Stage IV disease. Systemic therapy is a crucial aspect of their care. Patients with GCPM should have their tumors tested for HER2 and PD-L1 expression and microsatellite instability for potential targeted therapies. If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index [PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.

Gastric cancer is a significant global contributor to cancer-related mortality. Stage IV gastric cancer represents a significant percentage of patients in Western countries, with peritoneal dissemination being the most prevalent site. Peritoneal disease comprises two distinct entities, macroscopic (P1) and microscopic (P0CY1), which are associated with poor long-term survival rates. Although the present standard of treatment is palliative chemotherapy, a global controversy has arisen concerning specific patients with limited disease burden or conversion to negative lavage cytology following chemotherapy. Available approaches include systemic or intraperitoneal chemotherapy, upfront gastrectomy, and conversion surgery. This review consolidated the current evidence regarding multimodal management, indicating prolonged survival for this distinct subgroup of patients. Considering the complexity of peritoneal metastases, the potential of the multimodal approach unveils promising prospects for identifying the optimal treatment for this particular subset of stage IV patients and thus enhancing their survival outcomes.

Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes.

In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression.

We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0).

We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

Prior work has established hyperthermic intraperitoneal chemotherapy (HIPEC) administration as a safe treatment option for select patients with gastric adenocarcinoma and carcinomatosis. However, identifying patients who will maximally benefit from HIPEC remains unclear. This study assessed a single-institution experience with HIPEC for metastatic gastric cancer to identify variables associated with improved survival.

A database of patients treated for metastatic gastric adenocarcinoma at MD Anderson Cancer Center from 2013 to 2022 was queried for patients undergoing HIPEC as part of their treatment regimen. Patients were stratified by overall survival (OS)≥36 months or <36 months and assessed along demographic and clinicopathologic variables to identify factors associated with OS ≥ 36 months.

Among 104 patients, 1,2, and 3-year OS from diagnosis was 89 %,44 %, and 18 %. Patients with OS ≥ 36 months were more likely to have moderately differentiated tumors, positive cytology only (i.e. no visible carcinomatosis), and lower peritoneal cancer index (PCI) than those with OS < 36 months (p = 0.002, p = 0.01, p = 0.001,respectively). Groups did not otherwise differ with respect to demographic parameters or treatment or pathologic details. Among patients who underwent gastrectomy, those with OS < 36 months had higher pathologic T and N category (p = 0.003 and p = 0.02, respectively). Postoperative mortality was zero in both groups among patients undergoing gastrectomy.

HIPEC may provide more durable survival benefit among patients with metastatic gastric cancer with moderately differentiated disease, low PCI, and positive cytology alone. Additionally, among patients who undergo gastrectomy, higher final pathologic T and N category are associated with worse survival. Trials are needed to compare 3-year OS rates in patients treated with HIPEC versus systemic therapy alone.

This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC).

A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site.

The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex.

These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.

To improve care for patients with colorectal peritoneal metastases (CRC-PM) or pseudomyxoma peritonei (PMP), the Dutch CRS-HIPEC quality registry was initiated in 2019. The aims are to describe the development and content of this registry and to give insight into the data collected during the first years.

The registry is an observational cohort in the Netherlands. All patients with CRC-PM or PMP who intend to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) from 6 hospitals are included. Clinical data and outcomes (including hospital variation) were analyzed.

In 2019-2022, 889 patients were included in the CRS-HIPEC quality registry: 749 (84 %) with CRC-PM and 140 (16 %) with PMP. Peritoneal metastases were diagnosed synchronously in 51 % of CRC-PM patients and in 94 % of PMP patients. In patients undergoing complete CRS, the median peritoneal cancer index was 8 (IQR 4-13) for CRC-PM and 15 (IQR 6-26) for PMP. Complete cytoreduction was achieved in 639 CRC-PM patients (97 %) and 108 PMP patients (82 %). HIPEC was mainly performed with mitomycin C (CRC-PM: 94 %, PMP: 92 %). Major postoperative complications (Clavien-Dindo grade ≥3) occurred in 148 CRC-PM patients (22 %) and 30 PMP patients (23 %) with 90-day mortality rates of 2 %. In CRC-PM, differences between hospitals were observed regarding proportions of diagnostic laparoscopies/laparotomies, (neo)adjuvant treatment, ostomy formations and re-admissions.

The CRS-HIPEC quality registry provides insight into the outcomes of CRS-HIPEC and enables clinical auditing and observational cohort studies aiming to improve treatment outcomes for patients with CRC-PM and PMP.

Since 2016, staging laparoscopy has been implemented in the diagnostic workup of patients with gastric cancer. Staging laparoscopy aims to detect incurable disease (peritoneal metastases and irresectable tumors) and to prevent futile laparotomies.

In this population-based nationwide study, we sought patient- and tumor characteristics associated with undergoing a staging laparoscopy. Additionally, we analyzed the prevalence of synchronous peritoneal metastases, the outcome of the staging laparoscopy and its clinical impact on treatment decisions. All patients diagnosed with non-cardia gastric cancer from the Netherlands Cancer Registry between 2016 and 2021 were included.

Alongside tumor characteristics, patient characteristics such as younger age, absence of comorbidities and lower WHO performance status were associated with performing a staging laparoscopy. In the study period, an increase in the proportion of patients who underwent a staging laparoscopy was observed, from 19.6% in 2016 to 32.3% in 2021 (p-value<0.001). In the same period, the prevalence of synchronous peritoneal metastases increased from 25% to 31%. In 37.6% of the patients who had the outcome of their staging laparoscopy reported, had incurable disease diagnosed during staging laparoscopy. Significantly less of these patients were treated with triplet regimens as compared to patients with a negative staging laparoscopy (18.5 vs. 76.3%; p-value<0.001).

The implementation of staging laparoscopy in gastric cancer patients paralleled the increase in diagnosis of incurable disease and a decrease in the application of triplet systemic therapies in these patients.

We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.

We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.

The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons.

We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges.

In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation).

More randomised controlled trials are necessary.

This study is registered as PROSPERO CRD42019130504.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

PIPAC is a new surgical procedure and a viable treatment option for PSM patients, due to promising therapeutic outcomes, minimal invasiveness, limited surgical morbidity, and systemic toxicity side effects. However, its implementation throughout hospitals is hard to obtain due to its fragile economical sustainability. A retrospective health economic analysis was conducted in order to evaluate the cost of hospitalization for patients undergoing PIPAC treatment at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, in Rome. The average cost of a PIPAC procedure was defined based on the cost of surgery (cost of surgical material, operating room, intraperitoneal chemotherapy), hospital stay, diagnostic examinations, and drugs used during the stay. A total of 493 PIPAC procedures were performed on 222 patients with peritoneal metastases or primary peritoneal cancer from 2017 to 2023. Since the mean remuneration for each PIPAC hospitalization is €5916 and the mean expenditure per hospitalization is €6538, this results in an operating profit per PIPAC hospitalization of -€622. The reimbursement of PIPAC treatment by the Italian National Health System currently only partially covers the hospital's costs. Development of specific codes and adequate reimbursement for PIPAC by recognizing this procedure as a proper treatment for peritoneal carcinomatosis is essential.

Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible.

A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement.

The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy.

As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid. Patients were retrospectively grouped into: a positive group (with PD) and a negative group (without PD). Detectable mutations were found in the primary tumor of 68% (n = 19). Sensitivity of PD detection by tumor-guided cfDNA analysis was 91%, compared to 64% by conventional cytology. Within the positive group (n = 11), tumor-guided cfDNA was detected in all patients with ascites samples (4/4, 100%) and in 86% (6/7) of the lavage samples, opposed to 4/4 (100%) patients with ascites and 43% (3/7) with lavage by conventional cytology. Within the negative group (n = 8), conventional cytology was negative for all samples. In two patients, tumor-guided cfDNA was detected in peritoneal lavage fluid. Interestingly, these 2 patients developed PD within 6 months, suggesting a prognostic value of tumor-guided cfDNA detection. This study showed that tumor-guided cfDNA detection in peritoneal fluids of GC patients is feasible and superior to conventional cytology in detecting PD.

Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging.

In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations).

18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis.

For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs.

NCT03208621. This trial was registered prospectively on 30-06-2017.

Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease.

A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality.

The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials.

IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

The goal of a gastric cancer operation is a microscopically negative resection margin and D2 lymphadenectomy. Minimally invasive techniques (laparoscopic and robotic) have been proven to be equivalent for oncologic care, yet with faster recovery. Endoscopic mucosal resection can be used for T1a N0 tumor resection. Better understanding of hereditary gastric cancer and molecular subtypes has led to specialized recommendations for MSI-high tumors and patients with pathogenic CDH1 mutations. In the future, surgical management will support minimally invasive approaches and personalized cancer care based on subtype.

The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).

Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD.

Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended.

These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL is important given ongoing improvements in diagnostic imaging and treatment. As contemporary data from European centres are sparse, this retrospective cohort study aimed to assess the yield of DL in patients with potentially curable gastric cancer, and to identify predictive factors for peritoneal metastases.

Patients with adenocarcinoma of the stomach, treated between January 2016 and December 2018, were identified from institutional databases of two high volume European Upper-GI centres. Patients who underwent a DL with peritoneal lavage for potentially curable disease after clinical staging with imaging (cT1-4N0-3M0) were included. The primary outcome was the proportion of patients with a positive DL, defined as macroscopic metastatic disease, positive peritoneal cytology washings (PC+) or locally irresectable disease.

Some 80 of 327 included patients (24.5%) had a positive DL, excluding these patients from neoadjuvant treatment (66 of 327; 20.2%) and/or surgical resection (76 of 327; 23.2%). In 34 of 327 patients (10.3%), macroscopic metastatic disease was seen, with peritoneal deposits in 30 of these patients. Only 16 of 30 patients with peritoneal disease had positive cytology. Some 41 of 327 patients (12.5%) that underwent DL had PC+ in the absence of macroscopic metastases and five patients (1.5%) had an irresectable primary tumour. Diffuse type carcinoma had the highest risk of peritoneal dissemination, irrespective of cT and cN categories.

The diagnostic yield of staging laparoscopy is high, changing the management in approximately one quarter of patients. DL should be considered in patients with diffuse type carcinoma irrespective of cT and cN categories.

The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.

Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of affected patients' prognoses. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with favorable long-term outcomes in carefully selected patients with peritoneal metastases (PM). We aim to summarize the current results about the initial malignancies and their peritoneal spreads. The current literature has been scrutinized, and studies between 2016 and 2022 were included wherein long-term, progression-free (PFS), and overall survival (OS) data were considered relevant information. Medline, Embase, and Google Scholar have been the main sources. Hereby, we cover all the primer malignancies: gastric, ovarian, and colorectal cancers with peritoneal metastases (PM), malignant peritoneal mesothelioma, and pseudomyxoma peritonei. Examining the advances in the current peer-reviewed literature about the indications of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), target groups, risk factors, and other influencing elements, we intend to provide a complex state-of-the-art report, establishing the relevant aspects of that emerging treatment method.

The clinical significance of tumor-positive peritoneal cytology (CYT+) in gastric cancer (GC) patients is unclear. This nationwide cohort study aimed to i) assess the frequency of cytological analysis at staging laparoscopy; ii) determine the prevalence of CYT+GC; and iii) compare overall survival (OS) in CYT+ patients versus those with (PM+) and those without (PM-) macroscopic peritoneal disease.

All patients diagnosed with cT1-4, cN0-2 and M0 or synchronous PM GC between 2016-2021 were identified in the Netherlands Cancer Registry database and linked to the nationwide pathology database.

A total of 4397 patients was included, of which 40 % underwent cytological assessment following staging laparoscopy (863/1745). The prevalence of CYT+ was 8 %. A total of 69 patients had CYT+(1.6 %), 789 (17.9 %) had PM+ and 3539 (80.5 %) had PM- disease. Hazard ratio for OS in CYT+ versus PM+ was 0.86 (95 %CI 0.64-1.17, p-value=0.338), and in PM- versus PM+0.43 (95 %CI 0.38-0.49, p-value<0.001). No survival difference was found between systemic chemotherapy versus surgical resection in CYT+ patients.

In this nationwide study, OS for gastric cancer patients with CYT+ was equally unfavorable as for those with PM+ and significantly worse as compared to those with PM-. The optimal treatment strategy has yet to be established.

Systemic chemotherapy for gastric cancer with peritoneal metastasis has limited clinical benefit; for those with intraoperative detection of occult peritoneal metastasis, cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative treatment. However, the feasibility and effects of this modality and criteria for selecting suitable groups remain unclear. This study aimed to explore the safety and efficacy of laparoscopic cytoreductive surgery (L-CRS) followed by HIPEC in gastric cancer with limited peritoneal metastasis, and this study also aimed to determine the optimized cut-off of the peritoneal cancer index.

Between March 2017 and November 2019, patients diagnosed with gastric cancer peritoneal metastases by using laparoscopy and the Sugarbaker peritoneal cancer index of ≤12 were eligible for inclusion. All patients received L-CRS (including gastrectomy with D2 lymph node dissection) and resection of visible peritoneal metastasis, followed by post-operative HIPEC, and systemic chemotherapy. The primary end points were median progression-free survival and median survival time, and the secondary outcomes were morbidity and mortality within 30 days after surgery.

Thirty patients were eligible for analysis, of whom 19 (63.3%) were female, and the overall mean age was 53.0 years. The post-operative morbidity was 20% and the severe complication rate was 10%. The median survival time was 27.0 months with a 2-year overall survival rate of 52.3% and median progression-free survival was 14.0 months with a 2-year progression-free survival of 30.4%.

L-CRS followed by HIPEC can be safely performed for gastric cancer with limited peritoneal metastasis and potential survival benefits.

Gastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting.

We constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases.

In the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model.

The presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

The role of surgery in stage IV gastric cancer with peritoneal metastasis (PM) remains unclear. The objective of the current single-center study was to define the impact of gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on outcomes among Central European GC patients with limited peritoneal disease progression after neoadjuvant chemotherapy (NAC).

Patients with histologically confirmed GC who underwent curative-intent multimodal treatment between 2013 and 2023 were included. Patients without adenocarcinoma, who did not undergo gastrectomy, had early (cT1) or metastatic GC at the time of initial diagnosis, who underwent multivisceral resection, incomplete cytoreduction or palliative care, died before planned curative-intent treatment, or had incomplete clinical or pathological missing information were excluded.

A total of 74 patients who underwent curative-intent treatment for GC with PM were included in the final analytic cohort. Patients who underwent gastrectomy with CRS+HIPEC were less likely to achieve TOO (CRS+HIPEC: 28% vs. CRS: 57.1%, p = 0.033) compared with individuals after CRS alone. Specifically, patients who underwent gastrectomy with CRS+HIPEC had a higher likelihood of postoperative complications (CRS+HIPEC: 48% vs. CRS: 20.4%, p = 0.018) and longer hospital LOS (median, CRS+HIPEC: 12 vs. CRS: 10, p = 0.019). While administration of HIPEC did not impact long-term survival (median OS, CRS+HIPEC: 16 months vs. CRS: 12 months, p = 0.55), postoperative complications (median OS, CCI < 30:16 months vs. CCI > 30:5 months, p = 0.024) and ICU stay (median OS, no ICU stay: 16 months vs. ICU stay: 5 months, p = 0.008) were associated with worsened long-term survival among GC patients with PM.

Data from the current study demonstrated a lack of survival benefit among advanced GC patients with PM undergoing gastrectomy with CRS+HIPEC when compared with individuals after gastrectomy with CRS alone. Administration of perioperative chemotherapy and achievement of TO failed to withstand the peritoneal disease progression during NAC.

We reviewed outcomes following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal or colorectal neoplasms and evaluated key prognostic indicators for treatment.

All patients who underwent cytoreductive surgery/HIPEC for appendiceal and colorectal neoplasms were identified from an IRB-approved database. Patient demographics, operative reports, and postoperative outcomes were reviewed.

110 patients [median age 54.5 (18-79) years, 55% male] were included. Primary tumor location was colorectal (58; 52.7%) and appendiceal (52; 47.3%). 28.2%, .9%, and 12.7% had right, left, and sigmoid tumors, respectively; 11.8% had rectal tumors. 12/13 rectal cancer patients underwent preoperative radiotherapy. Mean Peritoneal Cancer Index was 9.6 ± 7.7; complete cytoreduction was achieved in 90.9%. 53.6% developed postoperative complications. Reoperation, perioperative mortality, and 30-day readmission rates were 1.8%, .09%, and 13.6%, respectively. Recurrence at a median of 11.1 months was 48.2%; overall survival at 1 and 2 years was 84% and 56.8%, respectively; disease-free survival was 60.8% and 33.7%, respectively, at a median follow-up of 16.8 (0-86.8) months. Univariate analysis of preoperative chemotherapy, primary malignancy location, primary tumor perforated or obstructive, postoperative bleeding complication, and pathology of adenocarcinoma, mucinous adenocarcinoma and negative lymph nodes were identified as possible predictive factors of survival. Multivariate logistic regression analysis showed that preoperative chemotherapy (P < .001), perforated tumor (P = .003), and postoperative intra-abdominal bleeding (P < .001) were independent prognostic indicators for survival.

Cytoreductive surgery/HIPEC for colorectal and appendiceal neoplasms has low mortality and high completeness of cytoreduction score. Preoperative chemotherapy, primary tumor perforation, and postoperative bleeding are adverse risk factors for survival.