Gastric cancer peritoneal metastases

Why stomach cancer goes to the peritoneum

The stomach is a hollow organ with a wall of several layers, and the outermost layer, the serosa, is in fact peritoneum. When a tumour grows through the whole wall and reaches that outer face, its cells sit in direct contact with the abdominal cavity. They shed, float in the small amount of fluid inside, and settle wherever gravity and the movement of the bowel carry them: the floor of the pelvis, the space under the right diaphragm, the omentum. It is the logic of a seed in a greenhouse — it does not need to travel through the bloodstream; it only needs to fall.

Not every stomach cancer does this with the same ease. The diffuse type of the Lauren classification, and in particular the signet-ring cell variant, grows by infiltrating the wall rather than forming a mass, is detected later, and reaches the serosa more often. When it thickens the whole stomach it is called linitis plastica. These tumours also respond worst to chemotherapy and most often recur in the peritoneum after an apparently curative gastrectomy.

Surgery on the stomach itself also counts: handling a tumour that has already reached the serosa can release cells into the cavity. That is why intraperitoneal treatments given at the time of gastrectomy have been studied for years, with results that remain inconclusive.

Risk factors for peritoneal spread (serosal invasion, diffuse type, signet-ring cells, nodal involvement): Thomassen I, et al. International Journal of Cancer, 2014, and the author's monograph on peritoneal carcinomatosis.

How often it happens

More often than is generally assumed. In the Dutch population registry, which followed more than five thousand patients with gastric cancer, roughly one in seven already had peritoneal disease at diagnosis. Among those presenting with metastases, the peritoneum was the most frequent site, involved in around a third or more of cases, and often the only site.

The other route is recurrence. After a gastrectomy with curative intent, the peritoneum is where the disease most often reappears, particularly if the tumour had reached the serosa or involved lymph nodes. That recurrence usually happens within the first two years and is frequently not well seen on CT until it is already extensive.

CT systematically underestimates this disease: peritoneal nodules of a few millimetres are not seen, and even less so on the small bowel. The true figure is therefore probably higher than image-based series record.

Thomassen I, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. International Journal of Cancer, 2014 (more than 5,000 patients, the Netherlands, 1995–2011).

Staging laparoscopy and peritoneal cytology

Because CT falls short, before a curative-intent treatment is decided for a gastric cancer that already grows through the wall or has suspicious nodes, a staging laparoscopy is performed: a short operation through two or three one-centimetre incisions, in which the surgeon inspects the whole cavity and takes samples. International guidelines recommend it before perioperative chemotherapy in locally advanced tumours.

Something else is done at that laparoscopy that matters as much as looking: the cavity is washed with saline, the fluid is collected, and it is examined for tumour cells. This is peritoneal cytology. If positive it is called CY1, and it means there are loose cells even though no nodule can be seen.

The current TNM classification, the eighth edition of the AJCC manual, is unambiguous: positive cytology counts as distant metastasis, M1, and therefore as stage IV — exactly as if visible nodules were present. It is hard news to receive with an abdomen that looks clean, but it reflects what happens next: most of these patients go on to develop visible peritoneal disease if they are simply operated on.

Laparoscopy finds occult peritoneal disease, missed on CT, in a meaningful share of locally advanced tumours: in published series, of the order of one patient in five, and more in diffuse-type tumours. Each of those patients is spared a gastrectomy that would not have cured them.

Positive cytology (CY1) classified as M1: AJCC Cancer Staging Manual, 8th edition, 2017. Indication for staging laparoscopy: NCCN gastric cancer guidelines, current version. Diagnostic yield of laparoscopy: order of magnitude from published series; varies with patient selection.

What chemotherapy alone achieves

Systemic chemotherapy is the backbone of treatment for peritoneal disease of gastric origin, and that should be said before any surgery is discussed. Historically, median survival with chemotherapy in patients with gastric peritoneal carcinomatosis was between six and twelve months, and in population registries, which include those who received no treatment, it was shorter still.

With current regimens the picture has improved. In the Japanese and Korean trial that compared chemotherapy alone against gastrectomy plus chemotherapy in patients with a single non-curable factor, the chemotherapy-alone arm reached a median of 16.6 months, and removing the stomach did not improve on it: 14.3 months. That trial, REGATTA, closed a door that used to open too easily — operating on the primary tumour when metastases are present, for no better reason than to do something.

The next change has come from markers. The tumour is now tested for HER2, for PD-L1 expression and for claudin 18.2, and the result decides what is added to chemotherapy. In tumours with high PD-L1, adding immunotherapy with nivolumab to chemotherapy prolonged survival in the CheckMate 649 trial, and that combination is now first-line treatment in those patients. Peritoneal disease does not respond to systemic treatment as well as other sites, but it shares in the benefit.

What this means for you is concrete: before any operation is discussed, your tumour's markers must be known and its response to a well-chosen systemic treatment must be seen. No surgical decision is made before that.

Historical medians: Thomassen I, et al. Int J Cancer, 2014, and series collected in the author's monograph. REGATTA: Fujitani K, et al. Lancet Oncology, 2016 (175 patients; 16.6 versus 14.3 months). CheckMate 649: Janjigian YY, et al. Lancet, 2021. Biomarkers: NCCN gastric cancer guidelines, current version.

Cytoreductive surgery with HIPEC: what the trials say

This is the point of the page. Cytoreductive surgery means removing all visible disease from the abdomen, and HIPEC means then bathing the cavity in heated chemotherapy. In colorectal cancer, ovarian cancer and above all appendiceal pseudomyxoma, this operation has changed the history of the disease. In gastric cancer the data do not say the same, and they have to be read trial by trial.

The first randomised trial was Chinese, from 2011, with 68 patients: cytoreductive surgery alone against the same surgery plus HIPEC. Median survival rose from 6.5 to 11 months with the bath. It was positive, but small, single-centre, with patients who mostly had extensive disease, and with a control arm — surgery without the bath and without modern chemotherapy — that was already not standard treatment in Europe. That is why it did not change practice outside Asia.

The French CYTO-CHIP study, from 2019, compared retrospectively, with statistical adjustment, 277 patients operated on with and without HIPEC across nineteen centres: median survival was 18.8 months with HIPEC against 12.1 without, and around 20% were alive at five years against 6%. The benefit was concentrated in patients with very little disease — a PCI of 6 or less — and complete cytoreduction. It is the study that supports the idea that a subgroup does benefit. But it is not a randomised trial, and the patients given HIPEC were the ones who were better to begin with.

The German GASTRIPEC-I trial, published in 2024, randomised patients who had responded to chemotherapy to cytoreductive surgery with or without HIPEC. The bath did not change overall survival: around fifteen months in both arms. It did lengthen progression-free survival, from about three and a half months to about seven, and reduced distant recurrence — signals that deserve study, but not what the patient is asking about. The trial closed before recruiting all the patients planned, which limits its power.

And the trial that was missing — the one comparing the full operation against not operating: the Dutch PERISCOPE II, in patients with limited peritoneal disease who had responded to chemotherapy. Median survival was 15.7 months with cytoreductive surgery and HIPEC against 16.6 months with systemic treatment alone, with serious adverse events in 44% of the surgical arm against 6%, and it closed early for futility. In well-selected patients, operated on in experienced centres, the operation did not lengthen life and did add complications.

The honest reading of all this is the one already given on the general page for this disease: outside a structured trial, cytoreductive surgery with HIPEC for peritoneal metastases of gastric origin is not defensible today as standard treatment. That it is still offered in some places does not change what the data say.

Yang XJ, et al. Annals of Surgical Oncology, 2011 (68 patients; 6.5 versus 11.0 months). Bonnot PE, et al. CYTO-CHIP. Journal of Clinical Oncology, 2019 (277 patients; 18.8 versus 12.1 months). Rau B, et al. GASTRIPEC-I. Journal of Clinical Oncology, 2024. Quik JSE, et al. PERISCOPE II. Lancet Oncology, 2026 (15.7 versus 16.6 months; serious adverse events 44% versus 6%).

When it is considered, and on what conditions

Not being standard does not mean there is no patient for whom it is considered. Expert consensus statements — the 2020 Chicago Consensus and the recommendations of the international PSOGI group — agree on the conditions, and they are strict: peritoneal disease of very low volume, with a low PCI, of the order of six or less; a demonstrated response to systemic chemotherapy; a realistic prospect of removing all the disease; no metastases in other organs; good general condition; and a centre experienced in this surgery. And even then, the recommendation is to do it preferably within a clinical trial.

A variant of this idea is conversion surgery: patients who present with peritoneal disease, receive chemotherapy, respond strikingly — the cytology turns negative, the nodules disappear at a second laparoscopy — and are then operated on with curative intent. Japanese and Korean series report long medians in the patients who reach that operation and leave it with a complete resection. But these are series of those who got there: the patients who did not respond are not in the count, and that inflates the result.

Japan has also explored repeated intraperitoneal chemotherapy with paclitaxel through a catheter, alongside systemic treatment. The PHOENIX-GC trial, with 183 patients, did not meet its primary endpoint: median survival was 17.7 months against 15.2 with systemic chemotherapy alone, a difference that was not statistically significant. A later analysis, adjusted for the amount of ascites at baseline, suggested a benefit, which is why the strategy is still being studied. Suggesting is not proving, and that is how it should be told.

If your case meets those conditions, the reasonable step is for the committee of a peritoneal surgery unit to review it and, if one exists, to offer you a trial. If it does not meet them, offering you the operation is not doing more for you: it is exposing you to six to eight hours of surgery, with serious complications in close to half of those operated on, without a survival gain to justify it.

Chicago Consensus Working Group. Management of gastric metastases (The Chicago Consensus on peritoneal surface malignancies). Cancer, 2020. PHOENIX-GC: Ishigami H, et al. Journal of Clinical Oncology, 2018 (183 patients; 17.7 versus 15.2 months). Serious complications: surgical arm of PERISCOPE II, Lancet Oncology, 2026.

PIPAC: what it is and what it can offer

PIPAC stands for pressurised intraperitoneal aerosol chemotherapy. It is done by laparoscopy: two small incisions, the cavity is filled with gas as in any laparoscopy, and through a nebuliser the chemotherapy is sprayed as a fine aerosol that spreads across the whole peritoneal surface and is held there, under pressure, for about thirty minutes. It is then evacuated and the incisions are closed. It is like painting a room with a spray gun instead of a brush: it reaches every corner with very little product.

Three things set it apart from HIPEC. First, nothing is resected: it is not cytoreductive surgery, it is a way of delivering a drug. Second, the dose is very low, around a tenth of what would be given intravenously, so general side effects are minimal and the hospital stay is one to three days. Third, it is repeated: the usual pattern is a cycle every six weeks, alternating with systemic chemotherapy, and at each one the surgeon looks at the abdomen again, scores the PCI and takes biopsies. That makes it possible to know, under the microscope rather than on a scan, whether the disease is responding.

What has been published: phase II studies, in gastric cancer and in mixed series of several origins, show histological regression of the nodules in a substantial share of patients who complete several cycles, control of ascites in many of them, and a low rate of serious complications. Quality of life is maintained during treatment. In a minority of patients with a good response, PIPAC has served as a bridge to a cytoreductive surgery that was not possible at the outset.

What has not yet been published: that it prolongs survival compared with systemic chemotherapy alone. No completed randomised trial shows that, and the ones under way in Europe and Asia are what will tell. Until then, PIPAC is a treatment with palliative intent — controlling ascites, slowing peritoneal disease, maintaining quality of life — or a bridge in highly selected patients, and that is how it should be offered.

Review of the clinical evidence for PIPAC by indication: scoping review by the author and colleagues in Clinical and Translational Oncology, 2026. Prospective phase II study PIPAC-OPC2: Graversen M, et al. Annals of Surgical Oncology, 2023. Technique and dosing: original description by the Tübingen group (Solass W, Reymond MA, et al., 2014) and later European series.

Ascites and obstruction: what is always treated

Whatever is decided about surgery, two problems of this disease have treatment, and nobody should endure them without it.

Ascites is the fluid that the irritated membrane produces in excess, swelling the abdomen, taking away appetite and making breathing harder. It is treated by draining it through a needle — paracentesis — which can be repeated, or replaced by a permanent catheter if the fluid accumulates quickly. Systemic chemotherapy that works reduces ascites, and PIPAC controls it in a high proportion of patients, which is one of the strong reasons for considering it.

Bowel obstruction appears when peritoneal nodules fix or narrow a loop of intestine. The options run from least to most invasive: diet and medication, an endoscopic stent if the narrowing is in a reachable spot, a venting gastrostomy so the stomach does not fill, or a bypass operation or a stoma if there is a single point of obstruction and general condition allows. Choosing well among them is as much a part of peritoneal surgery as cytoreduction is.

Management of ascites and malignant obstruction: the author's practice and NCCN gastric cancer and palliative care guidelines, current version. Ascites control with PIPAC: phase II studies cited in the previous section.

How your case is assessed, and what a second opinion changes

In our unit, every patient with peritoneal disease of gastric origin is presented at a peritoneal tumour board with medical oncology, radiology, pathology and surgery. Histology and markers are reviewed, along with the extent of disease on imaging, and if it has not been done, a staging laparoscopy with cytology and PCI is proposed. If the case meets the conditions for cytoreductive surgery within a trial, the trial is explained to you. If you are a candidate for PIPAC, you are told what it can and cannot achieve. And if you are a candidate for none of that, you are told no, with the reasons, and you go on being treated.

That "no" is part of the job. An operation of six to eight hours, with serious complications in close to half of those operated on, which in the only trial that compared it did not lengthen life, should not be offered to anyone who does not fit the conditions that justify it. Saying so at the first visit, rather than discovering it after the operation, is the least we owe you.

A second opinion in a high-volume unit changes the decision in three specific situations. When no laparoscopy with cytology has been done and a gastrectomy is being planned: it can avoid an operation that would not cure, or confirm that it is appropriate. When you have responded well to chemotherapy and nobody has looked at the abdomen again: a new laparoscopy can open the door to conversion surgery or to a trial. And when you have been told there is nothing to be done: PIPAC, ascites control and trials are things to be done.

What to bring is the usual: the images in digital format, the pathology report with the markers, the reports of any previous operations or laparoscopies, and the chemotherapy schedule you received. With that, the case can be reviewed before the visit.

And what this page does not do: the figures you have read are medians from groups of selected patients. They are not your prognosis. That can only be given by looking at the histology, the images and the person.

Tumour board procedure and assessment criteria: the author's practice at Hospital General Universitario Gregorio Marañón, a CSUR national reference centre for peritoneal carcinomatosis.