Ovarian cancer that has spread to the peritoneum

Why ovarian cancer reaches the peritoneum so early

The ovary does not sit inside a hollow organ, as a colon or stomach tumour does, with a wall to cross before it can get out. It lies free inside the peritoneal cavity, bathed in the fluid there. A tumour growing on its surface is, from day one, in direct contact with the whole abdomen.

It is now known, too, that most high-grade serous tumours — the commonest type — do not start in the ovary at all but at the end of the fallopian tube, which opens into the cavity. Cells shed and fall into the peritoneal fluid like dust in a draughty room.

That fluid does not stand still. The movement of the diaphragm with each breath drives it from the pelvis upwards, along the right side, to beneath the diaphragm. That is why the disease is always found in the same places: the pelvis, the omentum, the right paracolic gutter and the dome of the right diaphragm. It is not chance; it is the path the fluid takes.

And because the peritoneum does not hurt, all of this happens in silence. The consequence is the figure that defines this disease: around 70% of patients are diagnosed at stage III or IV, with disease already outside the pelvis. In Spain, around 3,500 new cases are diagnosed each year.

Tubal origin of high-grade serous carcinoma and transcoelomic spread: Kurman RJ, Shih IeM. Am J Surg Pathol, 2010. Stage distribution at diagnosis: population registries (SEER; REDECAN/SEOM for the Spanish figures). The annual Spanish case count is a rounded registry estimate.

The stages, in plain words

Ovarian cancer is not staged with the usual TNM but with the FIGO classification, which says the same things under other names. It is worth translating, because it is what appears in your report.

• Stage I: disease confined to the ovaries or the tubes.
• Stage II: disease has left the ovaries but stays within the pelvis.
• Stage III: disease on the peritoneum outside the pelvis, or in the retroperitoneal lymph nodes. This is peritoneal carcinomatosis. It is subdivided by the size of the implants: IIIA if they are microscopic only, IIIB if they measure up to two centimetres, and IIIC if larger — including disease on the capsule of the liver or spleen.
• Stage IV: disease outside the abdomen — a pleural effusion containing tumour cells, distant lymph nodes — or inside the liver or spleen, within the organ rather than on its surface.

Prat J; FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet, 2014.

The factor that weighs most: leaving no visible disease

Of everything that can be measured in this disease, one figure predicts prognosis more than any other, and it is the one that depends on the operation: how much disease is left inside when the abdomen is closed.

The study that measures it best pooled the data of 3,126 patients from three trials of the German AGO group. When surgery left no visible residual disease, median survival was 99.1 months. When residual nodules of one to ten millimetres were left, 36.2 months. When residual disease over one centimetre was left, 29.6 months. The same patients, the same chemotherapy afterwards; what changed was what stayed inside.

Look at the size of the gap: between leaving nothing and leaving “a little” there is more than five years of difference in the median. Between leaving a little and leaving a lot, barely six months. That is why the goal of surgery has changed over twenty years: it used to be enough to leave residual nodules under one centimetre, which was called “optimal” surgery. Today the goal is to leave nothing visible, and anything else counts as incomplete.

This has a practical consequence worth understanding early: when a team decides whether to operate, the question is not whether it can remove a lot, but whether it can remove all of it. If the answer is no, the operation loses much of its purpose, and it is better to change the order and give chemotherapy first.

du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials (AGO-OVAR 3, 5 and 7). Cancer, 2009. Relationship between the rate of maximal cytoreduction and survival: Bristow RE, et al. J Clin Oncol, 2002.

Operating first or giving chemotherapy first

There are two ways to order the treatment. The classical one is to operate first — primary debulking surgery — and give six cycles of chemotherapy afterwards. The other is to give three cycles of chemotherapy first to shrink the disease, operate in the middle — interval debulking surgery — and complete the chemotherapy afterwards.

Two European trials compared the two orders. EORTC 55971, with 670 patients at stage IIIC and IV, gave median survivals of 29 and 30 months: the same. The British CHORUS trial, with 552 patients, gave 22.6 and 24.1 months: also the same. In both, interval surgery was shorter, with fewer serious complications and fewer postoperative deaths, and more often ended with no visible disease, because chemotherapy had already reduced what had to be removed.

That was read as meaning chemotherapy first is just as good and safer, and in many places it became the norm. The criticism made — with reason — was that in both trials the rates of complete surgery were low even in the primary surgery arm, under one patient in five in EORTC 55971, and that median survival in both arms fell short of what the most experienced surgical centres were publishing.

The TRUST trial was designed to settle that question: only centres that could demonstrate high rates of complete surgery took part, and it compared the two orders again. Its results were reported in 2025. The primary endpoint, overall survival, did not reach a statistically significant difference in favour of operating first, although time to progression was longer with primary surgery and the survival trend pointed the same way, particularly at stage III. It needs careful reading: it does not prove that operating first is better for everyone, but it does show that, in expert hands and when complete surgery is achievable, operating first is at least as good and probably somewhat better.

The practical conclusion today is the one in the guidelines: if the disease can be removed in full at a first operation and your general condition allows it, operate first. If not — because of the extent of disease, above all on the small bowel, or because of your condition — chemotherapy first and interval surgery. The decision requires seeing the disease properly, and in many centres it is completed with a diagnostic laparoscopy before deciding.

Vergote I, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer (EORTC 55971). N Engl J Med, 2010. Kehoe S, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS). Lancet, 2015. TRUST (AGO-OVAR OP.7): results reported in 2025; details subject to the full publication. Neoadjuvant guideline: Wright AA, et al. SGO/ASCO. J Clin Oncol, 2016.

What “ultra-radical” upper abdominal surgery means

Classical ovarian cancer surgery removed the uterus, ovaries, tubes and omentum, and cleared the pelvis. With that, in many patients, disease is left higher up: on the diaphragm, in the spleen, on the liver capsule, on the bowel. For years that disease was left behind and chemotherapy was relied on to deal with it.

What changed the outcome was deciding not to leave it. When a North American referral centre systematically incorporated upper abdominal procedures — stripping the peritoneum off the diaphragm, removing the spleen where necessary, resecting affected bowel segments, clearing the liver surface — the proportion of patients leaving theatre with no visible disease rose markedly, and survival rose with it. And another series from the same period showed something uncomfortable: within the same hospital, patients’ survival depended on how radical the surgeon who operated on them had been.

That is what is now called ultra-radical surgery, or upper abdominal cytoreduction. In practice it is the same operation described on the parent page — cytoreduction of the peritoneal surfaces — applied to ovarian cancer. Stripping the diaphragmatic peritoneum, removing the spleen and sometimes the tail of the pancreas, resecting lengths of bowel and joining them back, clearing the porta hepatis. It is hours of meticulous work, and those are the hours that separate a complete operation from an incomplete one.

This is where who operates matters. Gynaecological oncology is the specialty that leads ovarian cancer care, and in many centres it has taken on this surgery with excellence. But the upper abdominal procedures — diaphragm, spleen, bowel, liver — are those of the surgical oncologist who treats carcinomatosis of any origin, which is why in the units with the best results the two work together in the same theatre. The question worth asking is not which specialty operates on you, but how often the team operating on you finishes with no visible disease.

Chi DS, et al. Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol, 2009. Aletti GD, et al. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol, 2006. Surgical quality indicators: Querleu D, et al. ESGO. Int J Gynecol Cancer, 2016.

HIPEC in ovarian cancer: where it is proven and where it is not

HIPEC is the heated chemotherapy bath delivered inside the abdomen at the end of surgery, to reach what cannot be seen. In ovarian cancer it has solid proof in one specific situation, and weaker evidence elsewhere. The two need separating.

Where it is proven: at interval surgery. The Dutch OVHIPEC-1 trial enrolled 245 patients at stage III who had received three cycles of chemotherapy and were coming to interval surgery. All were operated on until the abdomen was clear or nearly clear, with residual nodules under 2.5 millimetres. Half then received a cisplatin bath at 40 degrees for ninety minutes. Median survival went from 33.9 to 45.7 months, a 33% reduction in the risk of death. At ten years, 16.1% of those operated on with HIPEC were alive against 10.9% of those operated on without it. And serious complications were the same in both arms: 27% against 25%.

A later Korean trial, with 184 patients, points the same way with a detail that matters: overall there was no significant difference, but in the subgroup operated on at interval surgery HIPEC was associated with longer survival, and in the subgroup operated on up front it was not. It is a subgroup reading and should be taken as one, but it agrees with what OVHIPEC-1 had shown.

Where it is not proven: at primary surgery, because no large trial has tested it there with a positive result. And in recurrence the evidence is less clear. The French CHIPOR trial, in patients with a first platinum-sensitive relapse, reported longer survival with HIPEC but no difference in time to the next progression, and a North American trial using carboplatin in the same setting found no benefit. On that evidence, HIPEC at recurrence is regarded as an option to discuss case by case, not a standard.

In summary: if you are going to interval surgery, at stage III, and the team can leave the abdomen clear, cisplatin HIPEC is backed by a randomised trial with ten-year follow-up and is among the options the guidelines contemplate. Outside that scenario it can be considered, but it must be said plainly that the proof is weaker.

van Driel WJ, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer (OVHIPEC-1). N Engl J Med, 2018. Aronson SL, et al. Cytoreductive surgery with or without HIPEC in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis. Lancet Oncol, 2023. Lim MC, et al. Survival after HIPEC and primary or interval cytoreductive surgery in ovarian cancer: a randomized clinical trial. JAMA Surg, 2022. Recurrence: Classe JM, et al. CHIPOR, reported 2023; Zivanovic O, et al. J Clin Oncol, 2021.

When the disease comes back: a second operation

Most patients with advanced ovarian cancer will relapse, even when the first operation was complete and the chemotherapy worked. For years the answer to that relapse was more chemotherapy alone. Whether operating again makes sense took a long time to answer, and the answer is yes — but not for everyone.

The German DESKTOP III trial selected 407 patients with a first relapse more than six months after finishing platinum and with three conditions: good general condition, little or no ascites, and a first operation that had been complete. This is what is called a positive AGO score. Half were operated on again before chemotherapy and half received chemotherapy alone. Median survival was 53.7 months with surgery against 46.0 without.

The detail that matters most sits inside that result: the benefit was concentrated in the patients whose second operation was complete, which was three in four. Those who were operated on and left with visible disease lived less long than those who were never operated on. It is the lesson of the first operation, stated more harshly: operating makes sense if everything can be removed, and if it cannot, it is better not to.

A US trial from the same period, GOG-0213, found no benefit from second surgery. The most likely difference lies in selection: it did not use the AGO score, and its patients frequently received bevacizumab, which may have diluted the effect. A third trial, from China, did find that surgery lengthened the time to next progression. Taken together, it is now accepted that surgery for recurrence benefits well-selected patients, in centres where complete surgery is achievable.

Harter P, et al. Randomized trial of cytoreductive surgery for relapsed ovarian cancer (DESKTOP III). N Engl J Med, 2021. Coleman RL, et al. Secondary surgical cytoreduction for recurrent ovarian cancer (GOG-0213). N Engl J Med, 2019. Shi T, et al. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1). Lancet Oncol, 2021.

What the medical oncologist does, and why the decision is a team one

Surgery is half the treatment. The other half is chemotherapy with carboplatin and paclitaxel, given before or after surgery depending on the order chosen, and what is now called maintenance treatment: drugs taken for months or years after chemotherapy ends to delay relapse.

More has changed in that field in ten years than in the thirty before. PARP inhibitors — olaparib, niraparib and others — have markedly lengthened the time without disease, above all in patients whose tumour carries a BRCA mutation or a defect in DNA repair, which is now tested for routinely. Bevacizumab, a drug acting against the tumour’s blood vessels, also has a role in selected cases.

All of that is the medical oncologist’s field, and this page goes no further into it than to orient you. What does matter is that the choice of treatment order, the decision whether to operate at relapse, and whether to add HIPEC are not made by one specialist alone. They are made in a board where gynaecological oncology, medical oncology, radiology, pathology and — in centres that treat carcinomatosis — peritoneal surgical oncology sit together. If your case has not been through a board like that, it is reasonable to ask that it should be.

PARP inhibitors as first-line maintenance: Moore K, et al. SOLO1. N Engl J Med, 2018; González-Martín A, et al. PRIMA. N Engl J Med, 2019; Ray-Coquard I, et al. PAOLA-1. N Engl J Med, 2019. Guidelines: NCCN Ovarian Cancer and the ESMO-ESGO consensus conference on ovarian cancer.

When a peritoneal surgical oncologist adds something, and when to seek another opinion

In most cases the gynaecological oncology team at your hospital manages ovarian cancer from start to finish, and so it should. There are three situations in which the experience of someone who operates on carcinomatosis of any origin changes what can be offered.

• Extensive disease in the upper abdomen: on the diaphragm, the spleen, the liver capsule or the small bowel. These are the procedures that decide whether the operation ends complete, and they are the ones least often performed outside peritoneal surgery units.
• A relapse in which a second operation is being considered. Removing disease from an abdomen already operated on, with adhesions and altered anatomy, is harder than the first time, and the margin between a complete and an incomplete operation is narrower.
• The case that has been called “inoperable”. Sometimes it is. Other times, what the word means is that it was not operable by the team that said so, with the means it had. The difference can only be known by looking at the imaging with other eyes and, often, with a laparoscopy.

Selection criteria and the author’s experience in the peritoneal carcinomatosis unit at Hospital General Universitario Gregorio Marañón, a designated CSUR reference centre for this disease.

What this page does not do

The figures you have read are medians from groups of patients selected for trials. A median of 45 months is not a date: it is the point at which half the group had died and the other half were still alive, and in every one of these trials there are patients many years beyond it. Where you fall is not something any number on this page can tell you.

A second opinion is reasonable if you have been told surgery is not possible, if you have been offered an operation and want to check who will do it and how, or if your case has not been discussed in a board that includes peritoneal surgery. It offends no one. What you need to bring is the CT in digital form, the pathology report with the BRCA result if it has been done, and the notes from any previous operations. And none of the three things that decide — how much disease there is and where, the biology of the tumour, and your general condition — can be assessed from a screen.