The Inner Lining

Cancers of the peritoneum, the membrane that lines the abdomen, were long treated as the end of the road. What they are, why they are hard to see, what radical surgery with heated chemotherapy can do, and what the trials really show.

The peritoneum is a thin, slippery membrane that lines the inside of the abdomen and wraps most of the organs in it, so that the bowel can slide as it moves. It is larger than it sounds. Measured in ten cadavers, it covered about 1.4 square metres, close to the surface area of the whole body by the usual formulas, and more than four-fifths of it lay on the organs themselves, with the small bowel and its mesentery alone accounting for 39 per cent.[1] For a cancer cell that has broken loose inside the abdomen, it is an enormous field to land on.

Cancers of this surface come in two kinds. A few start there: peritoneal mesothelioma, from the membrane’s own cells, and pseudomyxoma peritonei, in which a mucus-producing tumour, often of the appendix, fills the abdomen with jelly. Far more often the peritoneum is where other cancers spread: of the colon and rectum, stomach, ovary, pancreas and appendix. For a long time, either kind was regarded as incurable. A 2021 review by the leading groups in the field summed up how that view has changed: “the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients.”[2]

The key words are “in selected patients”. This essay, a companion to The Brakes Released on cancer immunotherapy, looks at how often cancers reach the peritoneum, why they are so hard to see there, what the operation that changed the field involves, and what forty years of trials have and have not shown, including several large ones published this year.

1.4 m²the surface area of the peritoneum, close to the whole body’s surface area by the usual formulas

11%of peritoneal deposits smaller than half a centimetre that a CT scan detects

63%of 2,298 patients with pseudomyxoma peritonei alive ten years after surgery with heated chemotherapy

0.5months of difference in median survival (41.7 against 41.2) when heated chemotherapy was added to surgery for colorectal cancer in the PRODIGE 7 trial

How it gets there

Seeds in the abdomen

Most cancers spread through the blood or the lymph. Peritoneal metastasis can take a shorter route: cells shed from a tumour that has grown through the wall of an organ, float in the fluid of the abdomen and settle on the membrane. In ovarian cancer this is the main route. The cancer cells “primarily disseminate within the peritoneal cavity and are only superficially invasive”; “carried by the peritoneal fluid, cancer cell spheroids overcome anoikis”, the death that normally follows when a cell loses its attachment, “and attach preferentially on the abdominal peritoneum or omentum”, the fatty apron that hangs from the stomach.[3] A review in The Lancet Oncology called this transcoelomic route the most common in ovarian cancer and the one “responsible for the greatest morbidity and mortality”.[4] More recent work describes a “complex, stepwise process” in which the tumour, the shed cells and the membrane all take part.[5]

Fig. 1 — How often common cancers reach the peritoneum, in three population registries. Colorectal: all 11,124 patients in Stockholm County, 1995–2007, at diagnosis (4.3%) or later (4.2%). Pancreatic and gastric: the Eindhoven cancer registry, at diagnosis only (Segelman et al. 2012; Thomassen et al. 2013, 2014).

How often it happens depends on the cancer. In Stockholm County, of all 11,124 patients with colorectal cancer diagnosed between 1995 and 2007, 8.3 per cent developed peritoneal metastases, half at diagnosis and half later; in 4.8 per cent the peritoneum was the only site of spread. Tumours that had grown through the bowel wall (stage T4) carried ten times the risk.[6] In the Netherlands, 14 per cent of patients with gastric cancer and 9 per cent with pancreatic cancer already had peritoneal spread at diagnosis.[7][8] Ovarian cancer is different in kind: most serous ovarian carcinomas, the commonest type, are diagnosed at stage III (51 per cent) or IV (29 per cent),[9] and stage III is defined largely by spread within the abdomen.

Fig. 2 — What peritoneal spread means for survival. Gastric cancer in the Eindhoven registry: patients with peritoneal metastases against those with no metastases at all (Thomassen et al. 2014). Colorectal cancer in two chemotherapy trials: patients with and without peritoneal metastases among those whose cancer had spread (Franko et al. 2012).

Peritoneal spread is also a worse kind of spread. In gastric cancer, median survival was 4 months with it against 14 without any metastases; in pancreatic cancer, “only 6 weeks”, with no improvement over the years studied.[7][8] In 2,095 patients in colorectal chemotherapy trials, median survival was 12.7 months with peritoneal metastases against 17.6 without,[10] and in a pooled analysis of 10,553 patients, cancers that had spread only to the peritoneum did worse than cancers that had spread only to another single organ.[11] It was against this background that surgeons began to treat the membrane directly.

The rare ones

Jelly and the membrane’s own cells

Two diseases start in the abdomen itself and are rare enough that most doctors never see them. Pseudomyxoma peritonei, in which a mucinous tumour, usually from the appendix, fills the abdomen with gelatinous material, was estimated at about one case per million people per year; Dutch nationwide pathology records found 267 patients in ten years, “approaching 2 per million per year”, and about one in five patients with a mucinous appendiceal tumour went on to develop it.[12] Peritoneal mesothelioma, from the membrane’s own cells, has an incidence of 0.5 to 3 per million a year; it is linked with asbestos less strongly than mesothelioma of the lining of the lungs, with “33% of diagnosed patients” having a history of exposure, and it affects women and younger people more often than mesothelioma of the lungs’ lining does.[13]

Because they spread slowly and stay in the abdomen for a long time, these are the diseases in which the radical operation described below has its best results.

Hard to see

Below the resolution of the scan

The deposits are often small and flat, scattered over a surface that folds around the bowel, and scans miss many of them. In one study comparing CT with what surgeons found at operation, CT detected only 11 per cent of nodules smaller than half a centimetre, against 94 per cent of those larger than 5 cm, and it “significantly underestimated” the extent of disease.[14] In another, CT underestimated the extent in a third of patients, by enough to change the treatment decision in 12 per cent.[15] A meta-analysis of 934 patients put CT’s overall sensitivity at 83 per cent and its specificity at 86 per cent.[16] That is why surgeons often look directly, through a laparoscope, before deciding whether a full operation is worthwhile.

Fig. 3 — Why peritoneal cancer is hard to see. Left: the share of peritoneal nodules detected by CT, by size (Koh et al. 2009). Right: the median fraction of tumour DNA among the DNA fragments in the blood (the maximum variant allele fraction) in patients with colorectal cancer that had spread only to the liver or only to the peritoneum (Bando et al. 2022).

Blood tests struggle too. Tumours shed fragments of their DNA into the blood, and these “liquid biopsies” are increasingly used to follow cancers. Peritoneal deposits shed very little. In patients with colorectal cancer, the median fraction of tumour DNA in the blood was 23.1 per cent when the cancer had spread only to the liver and 0.4 per cent when it had spread only to the peritoneum, and the blood test agreed with the tumour tissue on key mutations in 95.9 against 56.0 per cent of cases.[17] A second study found the same: peritoneal spread is associated with “significantly lower ctDNA levels”.[18]

Measuring it

Thirteen regions

What surgeons can see, they score. In 1996 Patrick Jacquet and Paul Sugarbaker proposed dividing the abdomen into thirteen regions, nine in a grid over the abdomen and four along the small bowel, and scoring each from 0 to 3 by the size of its largest deposit. The total, the Peritoneal Cancer Index, runs from 0 to 39.[19][20] A second score records what is left at the end of the operation: CC-0 if no disease is visible, CC-1 if the remaining nodules are smaller than 2.5 mm, and so on.[20]

Fig. 4 — The Peritoneal Cancer Index. Thirteen regions, each scored 0 to 3 by its largest deposit (Jacquet & Sugarbaker 1996). The scores shown are an invented example, not a patient.

Both numbers predict survival, independently of each other. The index “has been recognized as an independent prognostic indicator”,[14] and in the large series below, the extent of disease and the completeness of surgery were the strongest predictors of outcome.[21][22] In the first randomised trial, patients with disease in six or seven regions, or in whom it could not all be removed, had a “grave prognosis”.[23]

The operation

Remove everything, then wash

The treatment that changed the field has two parts. The first is cytoreductive surgery: removing every visible deposit, which can mean stripping large areas of the peritoneum and taking out parts of several organs. The second is HIPEC, hyperthermic intraperitoneal chemotherapy: before the abdomen is closed, a heated chemotherapy solution is circulated through it, to reach the cells too small to see.

Fig. 5 — Four decades of surgery and chemotherapy inside the abdomen: the events described in this essay. Teal for the development of the method; pink for the large randomised trials of the last decade.

The first heated chemotherapy perfusion of the abdomen was described in 1980, in a 35-year-old man with pseudomyxoma peritonei, perfused at 42 °C.[24] In 1995 Paul Sugarbaker described six “peritonectomy procedures” for removing the peritoneum region by region, writing that such situations “have been regarded as lethal”.[25] The combination spread to specialist centres around the world, including, from the early 2000s, the Portuguese Oncology Institute in Porto and Lisbon (see below).

Fig. 6 — Long-term survival in selected patients after surgery with heated chemotherapy: the international registry of pseudomyxoma peritonei (Chua et al. 2012), the international series of peritoneal mesothelioma (Yan et al. 2009), and the patients with colorectal cancer in the first randomised trial whose tumour was removed with only microscopic residue (Verwaal et al. 2008). These are selected patients in specialist centres, not everyone with the disease.

In the rare diseases the results are the strongest. Among 2,298 patients with pseudomyxoma peritonei treated in 16 centres, median survival was 196 months, more than sixteen years, and 63 per cent were alive at ten years; 2 per cent died after the operation and 24 per cent had major complications.[21] Among 405 patients with peritoneal mesothelioma, median survival was 53 months and 47 per cent were alive at five years; 2 per cent died after surgery and 31 per cent had serious complications.[22] Neither series had a control group, and the patients were those fit enough, and with disease limited enough, to be operated on. But for diseases whose usual course was measured in months to a few years, these are long survivals.

The trials

What heated chemotherapy adds

For the common cancers the evidence comes from randomised trials, and it is more mixed. The first, in the Netherlands, randomised 105 patients with colorectal cancer that had spread to the peritoneum to cytoreductive surgery with HIPEC or to chemotherapy alone. Median survival was 22.3 against 12.6 months; 8 per cent of the surgical patients died of the treatment.[23] At eight years, 45 per cent of the patients whose tumour had been removed with only microscopic residue were alive at five years.[26] But the chemotherapy in the control arm, fluorouracil and leucovorin, is weaker than what patients receive today, and the trial could not say whether the benefit came from the surgery or from the heated chemotherapy.

That question was answered in France in 2021. PRODIGE 7 randomised 265 patients with colorectal peritoneal metastases who were all having complete cytoreductive surgery to HIPEC with oxaliplatin or no HIPEC. Median overall survival was 41.7 against 41.2 months; serious complications at 60 days were more common with HIPEC, 26 against 15 per cent. The authors concluded that “cytoreductive surgery alone should be the cornerstone”.[27] Two trials of HIPEC to prevent peritoneal spread in high-risk colorectal cancer, PROPHYLOCHIP and COLOPEC, found no benefit either,[28][29] and in 2026 the Dutch CAIRO6 trial, which added chemotherapy before and after surgery with HIPEC, found median survival of 44 against 39 months, a difference that was not statistically significant, with more major complications (36 against 26 per cent).[30]

Fig. 7 — Nine randomised trials and what they found. Hazard ratios for overall survival where the abstract gives one (disease-free survival for PROPHYLOCHIP); below 1 favours the treatment. Teal: a significant benefit. Pink: none shown. The trials ask different questions, from surgery with HIPEC against chemotherapy (Verwaal, PERISCOPE II) to HIPEC added to surgery (PRODIGE 7, OVHIPEC-1, CHIPOR, HORSE, GASTRIPEC-I) and preventive surgery (PROPHYLOCHIP); see text.

Ovarian cancer gave the opposite answer. In OVHIPEC-1, 245 women with stage III ovarian cancer having surgery after initial chemotherapy were randomised to HIPEC with cisplatin or none. Median survival was 45.7 against 33.9 months, with similar rates of serious side effects;[31] after about ten years of follow-up the difference held, 44.9 against 33.3 months.[32] In 2024 the French CHIPOR trial found a benefit in recurrent ovarian cancer too, 54.3 against 45.8 months, though with more serious side effects (49 against 27 per cent),[33] while the smaller Italian HORSE trial found none.[34]

Gastric cancer has been the hardest. The German GASTRIPEC-I trial, stopped early for slow recruitment, found the same median survival in both arms, 14.9 months, though HIPEC delayed progression.[35] A large French study comparing similar patients, not randomised, had suggested a benefit,[36] but in 2026 the Dutch PERISCOPE II trial, which compared surgery with HIPEC against systemic treatment alone, found median survival of 15.7 against 16.6 months, serious adverse events in 44 against 6 per cent, and three treatment-related deaths, all after surgery; it was closed early because it could not show a benefit.[37]

So the operation works in some diseases and some patients, and what the heated chemotherapy adds depends on the cancer and the drug. The international society of peritoneal surgeons, PSOGI, said as much in its 2022 consensus: “Evidence was weak or very weak for 9/10 clinical questions”; it recommended against the short, high-dose oxaliplatin regimen used in PRODIGE 7, and concluded that “despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended”, preferably with mitomycin C.[38] A 2026 consensus of 148 surgeons from three societies set out standards for how the surgery itself should be done.[39]

Other routes

Aerosols and immune drugs

For patients who cannot have the operation, PIPAC, pressurised intraperitoneal aerosol chemotherapy, was introduced in 2011: chemotherapy sprayed as an aerosol into the abdomen through a laparoscope, at “10% of a usual systemic dose”.[40][41] By 2019 it had been used in 838 patients and 1,810 procedures, and a review concluded that it “can be considered as a treatment option for refractory, isolated peritoneal metastasis” but “needs to be validated”.[41] It still does: a 2026 review found that “no completed trial has included a comparator arm”, with two phase III trials recruiting.[42] A single-centre randomised phase II trial in Moscow, published in 2026, which added PIPAC to chemotherapy in women whose ovarian cancer could not be fully removed, reported large gains that remain to be confirmed elsewhere.[43]

The drugs of The Brakes Released reach the peritoneum too. Among 502 patients with colorectal cancer with broken mismatch repair treated with checkpoint inhibitors, those with peritoneal spread but no fluid in the abdomen did about as well as those without peritoneal spread, while those with ascites did much worse, with three times the risk of death.[44] In ovarian cancer, maintenance with a PARP inhibitor after chemotherapy kept 60 per cent of women with BRCA mutations free of progression at three years, against 27 per cent on placebo.[45]

In Portugal

Two programmes and a registry of procedures

Surgery with HIPEC is done in Portugal at specialist centres. In 2017 an editorial in the journal of the Portuguese Society of Surgery marked the fifteenth anniversary of the introduction of the approach in Portugal, first at the Portuguese Oncology Institute in Porto and then in Lisbon.[46] The Porto group’s early phase II study included 25 patients treated between 2001 and 2006, with complete cytoreduction in 88 per cent and major complications in 12 per cent;[47] by 2016–2020 it was reporting 259 procedures in 248 patients.[48] A PIPAC programme was described in 2022.[49] All the large series in this essay come from specialist centres that select their patients carefully, and their results should be read with that in mind.

Coda

What is known and what is not

Established

Peritoneal spread is common in colorectal, gastric, ovarian and pancreatic cancer and carries a worse prognosis than spread to many other sites. CT misses small deposits. In selected patients, complete removal of the disease gives long survival, above all in pseudomyxoma peritonei and peritoneal mesothelioma.

Strong evidence

HIPEC with cisplatin at interval surgery lengthens survival in stage III ovarian cancer. In colorectal cancer, oxaliplatin HIPEC added to complete surgery does not.

Uncertain

HIPEC with other drugs in colorectal cancer; HIPEC in recurrent ovarian cancer (one positive and one negative trial); PIPAC, which has no completed controlled trial.

Not shown

A survival benefit of surgery with HIPEC in gastric cancer with peritoneal spread, in two randomised trials.

The peritoneum shows how cancer treatment advances, unevenly. An operation once regarded as reckless now gives long lives to patients with rare diseases who would have had little hope; the same operation, tested more strictly in common cancers, turns out to help in some and not in others, and the heated chemotherapy that gave it its name is the part most in question. Surgeons in the field have run trials that tested their own methods, and published the negative answers. For patients, the lesson of all these numbers is that peritoneal spread is no longer a single verdict: what it means depends on the cancer, its extent, and where it is treated.

Open threads

Where this could go

Seeing it early. Scans and blood tests both miss peritoneal disease. Tests on the fluid of the abdomen itself, or better imaging, could find it when it is still small enough to remove completely.

Choosing the drug. The colorectal and ovarian trials used different drugs at different temperatures and durations. Which chemotherapy, if any, belongs in HIPEC for each cancer is still being tested.

Immunotherapy inside the abdomen. The peritoneum is a closed space full of immune cells. Delivering immune treatments directly into it, rather than by vein, is a logical next step that the trials have barely begun to test.

On method and tools

This essay was researched and written with Claude Opus 5.5 (Anthropic): human specification, editorial direction and critical review; machine research, drafting and figure generation. The subject was Luis’s choice. A research agent (Claude) gathered the sources, and every reference was then checked against its PubMed record; the two Portuguese surgery-journal articles were read in full. For most studies the figures and quotations come from the abstracts; Boussios et al. (2018) and Jäger et al. (2023) were read in their open-access full text. The figures are drawn by scripts/peritoneal.py from the published numbers named in their captions; there is no model in this essay, and the scores in the Peritoneal Cancer Index diagram are invented for illustration. The cover is a drawing, not data. This essay describes what studies have found; it is not medical advice.

Authored by: Luis Matos Ferreira — Physicist, Developer, Writer

Related essays on this blog

1. The Brakes Released — cancer immunotherapy: checkpoint drugs, CAR-T cells and personalised vaccines.
2. Cancer — an earlier survey here of new cancer treatments (2024).
3. The Second Reader — what AI is and is not doing in medicine, from breast screening to the ward.

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