Peritoneal Metastasis from Gastric
Cancer: State of Art
John D Spiliotis123*
1Director and Chairman 4th Department of Surgical and Surgical Oncology
2European Interbalkan Medical Center Thessaloniki, Greece
3Athens Medical Center Marousi, Athens, Greece
Submission:July 26, 2021; Published:July 30, 2021
*Corresponding author: John D Spiliotis, MD, PhD, FASPSM, Director and Chairman 4th Department of Surgical and Surgical Oncology, European Interbalkan Medical Center Thessaloniki, Greece, Athens Medical Center Marousi, Athens, Greece
How to cite this article: John D S. Peritoneal Metastasis from Gastric Cancer: State of Art. Open Access J Surg. 2021; 13(3): 555863 DOI: 10.19080/OAJS.2021.13.555863.
Peritoneal metastasis (PM) has traditionally been approached with therapeutic nihilism. Gastric Cancer is a lethal disease especially with the presence of PM. The standard treatment for Gastric cancer with PM is palliative systemic Chemotherapy with a survival of 6 months. The evolution of cytoreductive surgery (CRS) and hyperthermic intraoperative chemotherapy the last decade, however, has caused a paradigm shift in the treatment for PM. This article reviews the current literature date regarding the use of CRS/HIPEC for PM from gastric cancer.
Gastric Cancer remains a lethal disease and is the 3rd leading cause of death from cancer in the world [1, 2]. Peritoneal metastasis is the most common type of recurrence and cause of death in gastric cancer. Patients with locally advance disease (tumor penetrating deeper to mucosa) at time of diagnosis remain at high risk for peritoneal dissemination despite margin-negative resection . Peritoneal disease are present in 20-30% at primary diagnosis and 40-60% will have a peritoneal relapse as the only site of metastasis the first 2 years after curative resection [4, 5]. On the other hand, the presence of positive peritoneal Lavage cytology is classified as M1 and has as similar prognosis to that of macroscopic metastatic nodules. The most common treatment with medical oncologists’ guidelines recommend palliative systemic chemotherapy [6, 7] with poor survival outcomes. The role of CRS/HIPEC for gastric cancer has been evaluated both in an adjuvant setting for locally advanced disease with curative resection as well as in setting of peritoneal metastasis. There is an increasing evidence based mainly on retrospective information and in several prospective trials with encouraging survival results in selected cases. In this article we present the state-of-the-art opinions concerning the management of peritoneal metastasis in gastric disease.
Given the aggressive native of gastric cancer, the importance of patient selection for CRS/HIPEC in this setting cannot be stressed enough. We currently offer Hipec only in patients with low disease burden. The two most important prognostic factors for patients with gastric cancer with PM are the volume of peritoneal disease, estimated by the PCI and the possibility to achieve a complete cytoreduction according to the completeness cytoreduction score [8, 9]. As both factors are related, PCI assessment is crucial to select patients for CRS and HIPEC. In 2010, Glehen O et. al.  published the analysis of 159 patients with PM from gastric cancer. No patient with PCI higher than 19 survived at 6 months and no patient with PCI>12 survived at 3 years. So, this French study recommended that patient with PCI>12 should not be treated with CRS and HIPEC because the survival benefit is extremely low. In 2016 Chia et. al.  published an analysis of 81 patients treated with complete CRS (CC0/1) and HIPEC. Patients with PCI<7 had a median OS of 26,4 months versus 10,9 month for PCI≥7. So in this study patients with a PCI<7 and a complete CRS, there is a real possibility of Cure. In 2019 a Spanish study of 88 patients with PM from gastric cancer have the similar results with PCI<7 had a median OS of 26,1 months versus 18,9 m with PCI>7 . In the same study the 5-year survival rate was 46,8% with PCI<7 while those with PCI≥7 had a 5-year survival rate of 0%.
More recently in 2020 Rau B et. al.  from Germany has been
published with 235 patients. The median OS according to PCI was
18 months for PCI 0-6, 12 m for PCI 7-15 and 5 months with PCI
In western countries (Europe and USA) pre-and post-operative
systemic chemotherapy is the standard of care. The MAGIC trial
was published in 2007 has been the standard therapy of patients
with advance gastric cancer. Unfortunately, the role of this trial
in patients with PM offers a median OS benefit of 5,4 months in
patients with low cancer volume . The 2019 the publication
of FLOT4 trial has changed this standard of care and currently
the FLOT (Fluorouracil, leucovorin, oxaliplatin and docetaxel)
with 4 preoperative and 4 postoperative cycles is preferred. The
benefit of FLOT in localized tumors with peritoneal disease offers
a median OS 9,8 .
In early 2000 Japanese studies proposed the combination of
neoadjuvant intraperitoneal and systemic chemotherapy (NIPS).
Yonemura et. al.  published the results of NIPS in 2012 with
IP taxotere and cisplatin combined with systemic S-1. Ninety-six
patients were enrolled, CC0 was achieved in 70% and 36,8% of
patients had complete pathologic response . Another trial
examine the use of preoperative HIPEC without cytoreduction, 53
patients treated with 2 cycles of Laparoscopic neoadjuvant Hipec
(doxatel plus cisplatin). A significant PCI decrease was observed,
from a median PCI 14,2 to a median PCI 11,8 and the cytology
changed from positive to negative in 68% of cases.
Peritoneal metastasis remains the most common type of local
recurrence after gastric cancer and is associated with median
survival pf approximately 4 to 6 months . On the other hand,
the response rate to systemic chemotherapy for peritoneal
deposits is low, which puts into perspective the role of CRS/
HIPEC for these patients. A complete cytoreduction is the main
requirement to prolong survival. The CRS must be carried out in
referral centers with experience in the selection of patients .
There is a luck of phase III trials and CRS/HIPEC is not yet the
standard of care. A phase III randomized trial by Yang et. al. 
evaluated 68 patients were randomized into CRS alone (n=34)
versus CRS/HIPEC (n=34) with a median PCI in both groups, both
groups had the same proportion of patients (58,8%) undergoing
CCso/1. Median OS was 6,5 months in the CRS group versus 11
months in CRS/HIPEC group (p=0,046). Both groups had similar
rates of serious adverse effects (11,7 %in CRS vs 14,7 % CRS/
HIPEC, p=0,8). On subgroup analysis patients with metachronous
PM had worse survival than those with synchronous PM. Our
registry in Greece which compare metachronous vs synchronous PM from gastric cancer we don’t found any significance difference between two groups concerning the OS . Coccolini et. al.
 performed a meta-analysis to evaluate the impact of CRS/
HIPEC. Outcomes of 20 RCTS were evaluated which include 2145
patients (1152 surgery + IP chemotherapy vs 993 controls). CRS
and HIPEC was shown to increase the 3-year survival rates as well
as decrease in the overall recurrence rate. The main bias of this
study is that the authors did not distinguish patients with locally
advanced disease from those with peritoneal metastasis. In 2019
 published the propensity score study CYTO-CHIP comparing
180 patients treated with CRS and HIPEC versus 97 patients
treated only CRS. The patients treated with HIPEC had better
survival rates 18,8 months vs 12,1 months without mortality and
morbidity differences. The most important questions concerning
HIPEC in gastric cancer is the confusion between different
centers concerning drugs, doses, duration, and the administration
Many patients with diffuse PM from gastric cancer can develop
malignant ascites which decrease the quality of life of these
patients. The last 5 years a new procedure has been described
to improve the quality of life for patients with refractory ascites.
Pressurized intraperitoneal chemotherapy (PIPAC) is a closed
laparoscopic technique of chemotherapy administration. The
drug is administered aerosolized by an injector at high pressure
and achieves better penetration into the tissues . The clinical
response of the method in patients with gastric cancer was 91%
. There are ongoing trials evaluating the use of PIPAC as a
Based on current evidence, the therapeutic benefit of CRS/
HIPEC for treatment of PM from gastric cancer is difficult to refute.
Only patients with low PCI (≤6) can benefit from this multimodal
treatment. We need more randomize phase III studies concerning
the loco regional treatments with IP chemotherapy (HIPEC, PIPAC,
EPIC) for have the evidence to changing the therapeutic steps for
the management of PM from gastric cancer.