Simple SummaryGastric cancer with metastasis to the peritoneum carries a poor prognosis, with a 40% mortality rate. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). We have conducted a systematic review and meta-analysis of available studies on novel treatment strategies including HIPEC and PIPAC to evaluate their safety and efficacy. Through this, our study contextualizes their role in the current treatment pathways for advanced gastric cancer.AbstractBackground: Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. Results: The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53;p= 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52;p< 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61;p< 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35;p< 0.00001), which correlated with a peritoneal carcinomatosis index below 7. Conclusions: Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.