Treatment of peritoneal carcinomatosis: cytoreductive surgery combined with HIPEC
Cytoreductive surgery and the role of HIPEC in peritoneal metastases of colorectal origin
When cancer of the colon or rectum spreads to the peritoneum, the treatment strategy requires particularly careful assessment. It is not enough simply to confirm the presence of tumour implants within the abdomen. It is necessary to determine their extent, the affected regions, the biological behaviour of the disease and, above all, whether there is a reasonable chance of removing all visible disease through surgery.
For years, so-called peritoneal carcinomatosis was interpreted as a manifestation of advanced disease amenable only to systemic treatment and symptom management. Advances in oncological peritoneal surgery have made it possible to change this perspective in a specific group of patients.
In carefully selected cases, cytoreductive surgery can form part of a strategy aimed at achieving long-term control of the disease and, in certain circumstances, may be considered with the intention of potentially curing the patient. The procedure may be complemented by hyperthermic intraperitoneal chemotherapy, known as HIPEC.
Dr François Quénet, an international authority on the treatment of colorectal peritoneal metastases and head of the Peritoneal Carninomatous Disease Unit, summarises one of the essential principles of this approach: “Progress does not lie in operating on more patients, but in better identifying those who can truly benefit from complete cytoreduction as part of a well-planned oncological strategy.”
The indication for cytoreductive surgery with HIPEC, therefore, does not depend on a single test, an isolated figure or the mere diagnosis of peritoneal involvement. It requires an in-depth assessment of each individual’s disease and clinical situation.
What are peritoneal metastases of colorectal origin?
The peritoneum is a thin membrane that lines the inside of the abdomen and covers the surface of most of the organs within it.
When cells from a cancer of the colon or rectum reach this surface, tumour implants may appear in different regions of the abdominal cavity. This condition has traditionally been termed peritoneal carcinomatosis, although in current clinical practice the term ‘peritoneal metastases’ is increasingly used.
The condition may be diagnosed at the same time as the colorectal tumour or may develop months or years after its treatment. Nor does it present in the same way in all patients. In some cases, it affects limited areas; in others, the implants are numerous, involve anatomically challenging areas or are accompanied by metastases in other organs.
These differences determine the treatment options. The number of lesions is important, but so too are their location, their relationship with the small intestine and other vital structures, the speed at which the cancer has progressed, and its response to previous treatments.
As Dr Juan José Torrent explains, a diagnosis of peritoneal metastases describes a cancerous condition, but does not in itself allow us to predict what the treatment recommendation will be. Two patients with the same diagnosis may require different strategies because the distribution and biology of their disease are not the same.
When might surgery be considered?
Cytoreductive surgery is primarily considered when the disease is confined to or predominantly localised in the peritoneum, its extent is manageable, and there is a reasonable chance of removing all visible implants.
Not all patients meet these criteria. This is a major operation that may require resections in different areas of the abdomen and should only be proposed when the expected benefit outweighs its complexity.
The decisive question is not merely whether the patient is technically suitable for surgery. It is also necessary to determine whether the procedure can achieve a clinically meaningful oncological outcome without causing disproportionate functional loss or risk.
This assessment explains why the decision to proceed must be made in centres with specific expertise and within a multidisciplinary committee. The surgical opinion is fundamental, but it must be integrated with the assessments of medical oncology, radiology, pathology, anaesthetology, nutrition and other relevant specialities.
What is cytoreductive surgery?
The aim of cytoreductive surgery is to remove all visible tumour implants within the abdominal cavity.
It does not consist solely of removing the original colorectal tumour or partially reducing the tumour burden. Its aim is to achieve complete or virtually complete cytoreduction; that is, to leave no macroscopic disease or to limit any residual disease to minimal lesions, smaller than 2.5 mm.
During the operation, the surgical team systematically examines the different regions of the abdomen. Depending on where the disease is located, it may be necessary to remove areas of the peritoneum through peritonectomy procedures, resect the omentum, or operate on segments of the intestine and other infiltrated organs.
The extent of the operation varies considerably. Some cytoreductive surgeries require relatively localised procedures; others involve several resections and reconstructions within a single operation.
The ability to complete the surgery successfully is one of the main factors determining its value. If it is anticipated that a significant amount of visible disease will remain, the benefit may be considerably reduced. For this reason, the team’s experience is reflected not only in the technical execution but also in the ability to recognise when an operation can achieve its objective and when it is not proportionate.
What is HIPEC and what does it offer?
HIPEC stands for hyperthermic intraperitoneal chemotherapy. When indicated, it is administered into the abdomen after the surgical resection phase has been completed.
A specialised system is used to circulate a heated chemotherapy solution, whilst controlling the temperature, flow rate and exposure time. The aim is for the drug to come into direct contact with the peritoneal surfaces and act on any microscopic tumour cells that cannot be identified or removed visually.
Hyperthermia can enhance the local action of certain drugs. However, the penetration capacity of intraperitoneal chemotherapy is limited. Consequently, HIPEC cannot compensate for incomplete surgery nor eliminate any macroscopic implants remaining in the abdomen.
This distinction is crucial: cytoreductive surgery treats visible disease; HIPEC aims to target any potential residual microscopic disease. They are related procedures, but not equivalent. In some patients, they are performed together; in others, surgery alone, without HIPEC, may be indicated.
What the scientific evidence has shown
Research in recent years has made it possible to distinguish more clearly between the value of surgery and the potential added benefit of the various HIPEC protocols.
One of the most significant studies is the French PRODIGE 7 trial, led by Dr François Quénet and published in *The Lancet Oncology*. In patients with colorectal peritoneal metastases in whom complete or near-complete cytoreduction had been achieved, the study compared surgery alone with the same surgery followed by a short-duration oxaliplatin-based HIPEC regimen.
The addition of this specific regimen did not increase overall survival and was associated with a higher incidence of late post-operative complications. At the same time, the results reinforced the central role of complete surgical cytoreduction in appropriately selected patients.
For Dr Quénet, one of the trial’s main contributions was to distinguish between two issues that had previously often been presented as a single one:
“PRODIGE 7 confirmed the importance of cytoreductive surgery and showed that we cannot attribute the same effect to every form of HIPEC. The result must be interpreted taking into account the drug, the dose, the duration and the context in which it is administered”.
The study did not evaluate all possible forms of intraperitoneal chemotherapy. Subsequently, a consensus from the Peritoneal Surface Oncology Group International concluded that HIPEC could continue to be considered on a conditional basis following complete cytoreduction and expressed a preference for certain mitomycin C-based protocols.
An international analysis published in BJS Open in 2024 compared different HIPEC regimens in over 2,000 patients treated at numerous centres. The study found associations between the protocols used and clinical outcomes, but its retrospective nature prevents it from demonstrating that any one of them is superior. Its main significance lies in confirming that HIPEC is not a uniform procedure: the drug, dose and duration of exposure are important when interpreting the results.
The most prudent conclusion is that cytoreductive surgery retains a fundamental role when it can be performed comprehensively. The appropriateness of adding HIPEC should be assessed on a case-by-case basis, taking into account the characteristics of the case, the protocol used and the centre’s experience.
How patients are selected
Patient selection is probably the most important stage of the entire process. No single finding is sufficient to establish the indication.
Factors to be assessed include:
The extent and distribution of peritoneal metastases.
The possibility of removing all or virtually all visible disease.
Involvement of the small intestine, the mesentery and other critical anatomical areas.
The presence of metastases outside the peritoneum.
The histological and molecular characteristics of the tumour.
Response to systemic treatments.
The patient’s nutritional, functional and general condition.
The risk of the procedure weighed against the expected benefit.
The presence of metastases in other organs does not automatically rule out surgery in all cases. In certain, very specific situations, surgery may be considered as part of a combined strategy. However, extensive disease outside the peritoneum or rapid progression despite treatment usually reduces the expected benefit of a locoregional procedure.
Professor Luis González-Bayón emphasises that this decision must go beyond the technical feasibility of surgery: “The committee does not decide whether a procedure can be performed, but whether that procedure forms part of the best strategy for a specific individual. The extent of the tumour, its biology and the patient’s condition must be interpreted together’. This approach avoids the application of rigid criteria and allows the recommendation to be tailored to the actual complexity of the case.
The peritoneal carcinomatosis index
To describe the extent of the disease, specialists commonly use the peritoneal carcinomatosis index (PCI). The system divides the abdomen into thirteen regions and assigns a score based on the size of the implants found in each. The total score allows the peritoneal tumour burden to be estimated.
Generally speaking, a low PCI is usually associated with more limited disease and a greater likelihood of achieving complete cytoreduction. However, there is no single figure that should automatically be interpreted as an indication or contraindication.
The location can be just as important as the score. A small-volume disease that is widely distributed across the small intestine or situated around vital vascular structures may be more difficult to treat than one with a higher score but localised in resectable areas. Furthermore, imaging tests may underestimate small implants. The PCI estimated prior to surgery does not always correspond to that observed during surgical exploration.
It should therefore be understood as a tool for describing the disease and guiding decision-making, not as a substitute for expert assessment.
How the case is assessed prior to surgery
The assessment begins with a comprehensive review of the oncological history: the location and characteristics of the primary tumour, histopathology, molecular alterations, previous surgeries, treatments received and the course of the disease.
Computed tomography (CT) is usually the initial imaging test. In certain cases, magnetic resonance imaging (MRI), PET-CT or other scans may be used to better assess certain lesions or to rule out involvement of other organs.
Where significant doubts remain regarding the actual extent of the implants, a diagnostic laparoscopy may be considered. This procedure allows direct visualisation of the abdominal cavity, the taking of samples and a more accurate assessment of whether the disease can be resected.
The assessment is not limited to the tumour. It is also necessary to determine whether the patient can cope with a lengthy operation and a demanding recovery. Among other factors, cardiopulmonary, renal and hepatic function, nutritional status, functional capacity and associated conditions are assessed.
Dr Torrent emphasises that preparing the patient is not merely an administrative step prior to the operation, but an integral part of the treatment itself. Addressing malnutrition, improving physical fitness, reviewing medication and anticipating future needs can all contribute to a safer recovery.
The role of systemic chemotherapy
Cytoreductive surgery should not be viewed in isolation. In many patients, systemic chemotherapy forms part of the strategy either before or after the operation.
It may be used to control microscopic disease outside the peritoneum, treat other sites, assess tumour sensitivity or stabilise the disease whilst further investigations are carried out.
The sequence depends on multiple factors: whether the metastases appeared at the same time as the colorectal tumour or afterwards, the treatments already administered, molecular alterations and the observed course of the disease.
The response to chemotherapy provides information on the biological behaviour of the cancer. Rapid progression despite appropriate treatment may lead to a reconsideration of extensive surgery. Stable or treatment-responsive disease may be a favourable sign, although it does not in itself constitute an indication.
Coordination between medical oncology and surgical oncology enables the most appropriate timing to be chosen and the operation to be integrated into an overall treatment plan.
How the procedure is carried out
The surgery begins with a thorough examination of the abdomen. The team confirms the distribution of the implants, calculates the surgical PCI and assesses whether the intended objective can be achieved.
The affected areas are then removed using procedures tailored to each patient. It may be necessary to resect different areas of the peritoneum, the omentum, segments of the intestine or other infiltrated organs. The priority is to achieve complete removal of visible disease whilst maintaining a reasonable balance between oncological radicality, safety and functional preservation.
If it has been decided to incorporate HIPEC, this is administered according to a defined protocol once the resection phase has been completed. The total duration of the operation depends on the extent of the disease and the number of procedures required; therefore, there is no single timeframe applicable to all cases.
The complexity of these procedures requires close coordination between the surgical, anaesthetology, intensive care and specialist nursing teams, as well as those responsible for oncological follow-up.
Recovery and possible complications
After the operation, the patient remains under close observation. Depending on the extent of the surgery and their initial progress, they may require intensive care or admission to a post-operative care unit.
During the first few days, pain, kidney and respiratory function, fluid balance and bowel recovery are monitored. Food is gradually reintroduced, depending on digestive function and the extent of the resections performed.
Early mobilisation, respiratory physiotherapy and nutritional support help to reduce complications and restore independence. The length of hospital stay depends on the extent of the procedure and the patient’s individual progress.
After discharge, it is common to need several weeks to regain strength, appetite and the ability to carry out daily activities. Follow-up appointments allow for the assessment of wound healing, the analysis of histopathological results and a decision on whether to continue or restart systemic treatment.
Cytoreductive surgery is a major operation. It may be associated with infections, bleeding, respiratory complications, thrombosis, renal dysfunction, delayed bowel recovery or problems with digestive anastomoses, amongst other complications. HIPEC may add further effects related to the drug and protocol used.
The likelihood of these complications varies from patient to patient. It depends on the tumour burden, the extent of resection required, the duration of the operation and the patient’s pre-existing clinical condition. Providing information about the risks is not intended to cause alarm, but to enable an informed and proportionate decision.
What outcomes can be expected?
There is no single prognosis that applies to all people with colorectal peritoneal metastases.
Outcomes are determined by the initial extent of the disease, the feasibility of achieving complete cytoreduction, the biological characteristics of the tumour, the response to systemic treatment, the presence of metastases in other organs and the patient’s general condition.
In carefully selected patients, surgery can offer long-term control of the disease and, in around 20 per cent of patients, a cure is achieved. Even so, there is a risk of relapse both in the peritoneum and in other sites.
Treatment should not be presented as a guarantee of a cure, but rather as the best option for the treatment of peritoneal carcinomatosis. Its value lies in offering a specialised option when the anatomy and behaviour of the disease make it reasonable to expect a significant clinical benefit.
Statistics from studies describe outcomes for groups of patients. An individual’s prognosis should be explained after taking all aspects of the case into account.
What happens if surgery is not indicated?
Not being a candidate for cytoreductive surgery does not mean that there are no alternatives. Medical oncology offers various chemotherapy regimens, targeted therapies and immunotherapy for specific molecular profiles. The choice depends on the characteristics of the tumour, previous treatments and the clinical situation.
Procedures may also be carried out to relieve symptoms or resolve specific complications, such as a bowel obstruction or fluid build-up in the abdomen.
In some people, the situation may be reassessed following systemic treatment. The response to treatment, the progression of the lesions and the patient’s general condition may lead to a change in the initial strategy, although a disease considered unresectable does not always become operable.
The recommendation should form part of a comprehensive cancer management plan and should not be limited to deciding whether or not a particular technique can be applied.
Frequently asked questions
Are cytoreduction and HIPEC the same treatment?
No. Cytoreductive surgery is the procedure aimed at removing visible implants. HIPEC is chemotherapy administered inside the abdomen to target any possible microscopic residual disease.
Is HIPEC always administered after surgery?
No. Whether it is indicated depends on the type of disease, the available protocol, previous treatments and the team’s assessment. Cytoreductive surgery may be performed without HIPEC.
Can all patients with peritoneal metastases undergo surgery?
No. The decision depends on the extent and distribution of the disease, the feasibility of removing it, the tumour biology and the patient’s general condition.
Does HIPEC replace intravenous chemotherapy?
No. HIPEC acts locally within the abdomen. Systemic chemotherapy circulates throughout the body and serves a different purpose. Both may form part of the same treatment strategy.
Can the disease be cured?
Yes. In some selected patients, treatment may be considered with the aim of potentially curing the disease. However, there remains a risk of relapse.
A strategy tailored to each patient
Peritoneal metastases of colorectal origin are no longer interpreted in the same way as they were a few decades ago. Cytoreductive surgery, systemic treatments and a more precise understanding of tumour biology have expanded the therapeutic options for a specific group of patients.
Progress, however, does not lie in the widespread application of complex procedures. It lies in rigorous selection, determining whether it is possible to eliminate visible disease, and assessing whether the potential benefit outweighs the risks of the procedure.
Surgery remains central when complete cytoreduction can be achieved. HIPEC may complement treatment in selected situations, but its indication must take into account the protocol used and the evolving scientific evidence.
The team’s experience, multidisciplinary discussion and clear information enable the development of a strategy tailored not only to the disease, but also to the individual facing it.
The information in this article is provided for general awareness and does not replace an individualised medical assessment.
