HIPEC for stage 4 colon cancer: could this major operation actually help me? | Dr Dilanka De Silva

A 42-year-old lawyer. No bowel symptoms. No family history. Yet her first diagnosis was already stage 4 colon cancer.

Unfortunately, this can happen.

This patient was referred to me for genetic assessment after being diagnosed with colon cancer that had spread across the lining of her abdomen—the peritoneum.

Her CEA tumour marker was elevated at approximately 21, and testing of the cancer showed loss of the MLH1 protein.

At the same time, she was being assessed for a major treatment called cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

The obvious question was:

“Could HIPEC improve my chance of living longer—or would I be undergoing an enormous operation without enough benefit?”

The answer requires much more than simply knowing that the cancer has reached the peritoneum.

HIPEC for colon cancer may be appropriate for some carefully selected patients, but suitability depends on much more than the cancer simply reaching the peritoneum.

Some personal details have been adjusted to protect patient confidentiality.

Who is this article for?

This article may be helpful if:

• you have colon or colorectal cancer that has spread to the peritoneum;
• you have been referred to discuss HIPEC or cytoreductive surgery;
• you have been told you have a high or low Peritoneal Cancer Index;
• your tumour is MSI-high or mismatch-repair deficient;
• your pathology shows loss of MLH1; or
• you are considering a second opinion before a major abdominal operation.

The diamond answer

HIPEC is not automatically the right treatment simply because colon cancer has spread to the peritoneum.

For carefully selected patients whose disease may ultimately be completely removed, cytoreductive surgery can form part of a treatment strategy that may offer meaningful long-term disease control. The timing of surgery versus treatment that works throughout the body, such as chemotherapy or immunotherapy, should be decided by an experienced multidisciplinary team.

The controversial part is the heated chemotherapy itself.

In the major PRODIGE 7 randomised trial, adding short-duration oxaliplatin-based HIPEC to successful cytoreductive surgery did not improve overall survival and resulted in more serious complications by 60 days. Current ASCO guidance therefore recommends against adding this particular oxaliplatin-based HIPEC approach routinely.

So the first question should not simply be:

“Can I have HIPEC?”

It should be:

“Can an experienced surgical team remove all visible cancer—and what additional benefit, if any, is expected from the particular HIPEC treatment being proposed?”

What does HIPEC for colon cancer involve?

HIPEC stands for hyperthermic intraperitoneal chemotherapy.

When cytoreductive surgery and HIPEC are used together, the treatment has two components.

First, the surgeon removes visible cancer deposits from inside the abdomen. This is called cytoreductive surgery, or CRS.

If HIPEC is being used, heated chemotherapy is then circulated through the abdominal cavity for a defined period before being removed.

The idea is to expose microscopic cancer cells remaining within the abdomen to a high concentration of chemotherapy.

The important distinction for patients is:

Cytoreductive surgery removes visible cancer. HIPEC is an additional treatment given after that surgery.

They should not be treated as though they are the same intervention.

Why do only selected patients qualify?

This is a very large operation, and the potential benefit depends heavily on patient selection.

Current specialist consensus emphasises factors such as good general fitness, relatively limited peritoneal disease, acceptable surgical risk and—most importantly— a realistic expectation that surgeons can remove all visible cancer (complete cytoreduction). Extensive disease involving the small bowel or other surgically difficult areas can make complete removal impossible. There is no single PCI cut-off that applies to every patient or every specialist centre.

The amount of cancer within the abdomen is often described using the Peritoneal Cancer Index, or PCI.

In simple terms:

The PCI gives the surgical team an estimate of how widely the cancer is distributed throughout different areas of the abdomen.

Generally, a lower burden of disease makes complete removal more achievable, but the location of the deposits can matter just as much as the number.

Sometimes scans cannot show the full extent of peritoneal disease. A staging laparoscopy, or keyhole examination of the abdomen, may therefore be considered before committing to a much larger operation.

Three questions that matter most

1. Is the cancer confined to the peritoneum?

This is one of the first questions I would want answered.

A contrast-enhanced CT of the chest, abdomen and pelvis is usually central to staging. MRI can provide additional information about peritoneal disease in selected patients.

A PET scan is not automatically required for every patient, but it can sometimes help when curative-intent surgery is being considered and there is concern about cancer elsewhere.

PET also has limitations. Small peritoneal deposits and some low-FDG-uptake or mucus-producing cancers can be difficult to see. Current specialist guidance therefore recommends choosing CT, MRI and PET according to the clinical situation rather than relying on one scan alone.

2. Can all visible disease be removed?

This may be the most important surgical question.

ASCO recommends considering cytoreductive surgery only in appropriately selected patients where complete removal of the peritoneal metastases is considered achievable and there is no cancer elsewhere that would make a curative-intent operation unrealistic.

In PRODIGE 7, surgeons were able to remove all visible cancer in approximately 91 in every 100 patients, reflecting just how carefully patients were selected and the expertise of the centres involved.

HIPEC is unlikely to compensate for a situation where substantial visible cancer has to be left behind.

3. Does HIPEC add enough benefit beyond surgery?

For colorectal cancer, this is where the controversy lies.

Different centres have used different drugs, temperatures and treatment durations.

The strongest randomised evidence tested a short-duration, high-dose oxaliplatin HIPEC regimen. That treatment did not improve overall survival.

Some specialist centres still consider other forms of HIPEC, particularly those using a chemotherapy drug called mitomycin-C. However, we do not yet have strong evidence proving that these approaches improve survival.

That distinction matters.

What did PRODIGE 7 actually show?

PRODIGE 7 included 265 carefully selected patients with colorectal cancer that had spread to the peritoneum.

All underwent cytoreductive surgery. Half were also assigned to oxaliplatin-based HIPEC.

HIPEC did not extend overall survival

Median overall survival was:

• 41.7 months with cytoreductive surgery plus HIPEC
• 41.2 months with cytoreductive surgery alone

In patient language, the typical survival in the two groups differed by only about half a month, and statistically there was no survival advantage from adding the oxaliplatin HIPEC regimen.

Serious later complications were more common

By 60 days after surgery, serious complications (grade 3 or worse) occurred in approximately:

• 26 in every 100 patients who had surgery plus HIPEC
• 15 in every 100 patients who had surgery alone.

But there was also an important positive message

Both groups had median survival of more than 41 months, despite having metastatic colorectal cancer.

That should not be interpreted as proof that surgery alone caused that survival—the trial was not designed to compare surgery with no surgery.

However, together with the wider evidence, it supports the view that carefully selected patients with isolated peritoneal metastases can sometimes do remarkably well after successful cytoreductive surgery. ASCO notes that approximately 15 in every 100 patients in PRODIGE 7 experienced no disease progression during the five years following surgery.

Two important complications to understand

Cytoreductive surgery, with or without HIPEC, is major abdominal surgery.

One important problem is infection or an abdominal collection. This may require antibiotics, drainage and occasionally another procedure.

Another is a bowel leak (anastomotic leak), where an area of bowel that has been cut and rejoined does not heal completely and begins to leak.

A significant leak can cause severe infection, require another operation and sometimes lead to a temporary or permanent stoma. These are recognised complications of extensive cytoreductive surgery.

This is why patients should ask not only whether an operation can be done, but also about the experience and outcomes of the centre performing it.

Should CEA be high in stage 4 colon cancer?

Not necessarily.

CEA is a tumour marker that some colorectal cancers release into the bloodstream.

A CEA of approximately 21 was above the usual reference range and may provide a useful baseline for this patient.

If CEA falls during treatment and later rises, it can sometimes help us follow what the cancer is doing.

But CEA has important limitations:

• some advanced cancers produce very little CEA;
• a normal CEA does not exclude metastatic cancer;
• smoking and several non-cancerous conditions can increase CEA; and
• CEA cannot tell us whether someone is suitable for cytoreductive surgery or HIPEC.

I think of CEA primarily as one monitoring tool, not a measurement of exactly how much cancer is present.

Could the abdominal deposits be something other than colon cancer?

Before pathology is established, peritoneal abnormalities can have several causes.

They may represent colorectal or appendiceal cancer, ovarian or primary peritoneal malignancy, rarer diseases of the peritoneal lining, or occasionally non-cancerous inflammatory or infectious conditions.

This is why treatment should not be determined from the scan appearance alone.

Once pathology confirms that the deposits represent metastatic colon cancer, the important questions become where the disease is, how extensive it is, what its biology is and whether it can be completely removed.

Why is MLH1 loss so important?

This was another crucial part of my patient’s case.

MLH1 is one of the proteins involved in repairing mistakes when cells copy their DNA.

Loss of MLH1 on tumour testing raises concern for mismatch-repair deficiency (dMMR), although the complete MMR staining pattern and/or MSI testing should be reviewed.

This matters for two very different reasons.

It may completely change the treatment sequence

If further testing confirms that the cancer has a faulty DNA-repair system—called mismatch-repair deficient (dMMR) or microsatellite instability-high (MSI-H)—immunotherapy can be highly effective in metastatic colorectal cancer.

For example, in the first-line CheckMate 8HW study, at two years approximately 72 in every 100 patients receiving nivolumab plus ipilimumab were alive without their cancer progressing, compared with approximately 14 in every 100 treated with chemotherapy.

This is why I would not view HIPEC or cytoreductive surgery in isolation in a 42-year-old patient with MLH1 loss.

The tumour biology may change what should happen first.

It may raise the possibility of Lynch syndrome

Lynch syndrome is an inherited condition that increases the risk of colorectal, uterine and several other cancers.

A negative family history does not completely exclude Lynch syndrome.

But MLH1 loss also does not automatically mean that Lynch syndrome is present.

Many colorectal cancers lose MLH1 because of a change that occurred only inside the tumour rather than an inherited genetic alteration.

When MLH1 is lost, further tumour testing for BRAF V600E and/or a change called MLH1 promoter methylation can help determine whether the finding is more likely to be inherited or to have developed only within the cancer. MLH1 promoter methylation commonly points towards a non-inherited cause. Finding a BRAF V600E mutation usually makes Lynch syndrome much less likely, while not finding BRAF V600E does not by itself prove Lynch syndrome.

At only 42 years of age, I would take the genetics question particularly seriously and interpret the complete tumour findings with a cancer genetics team.

Tumour testing and inherited genetic testing are different

This distinction often causes confusion.

Tumour testing examines changes inside the cancer itself. These results can influence treatment—for example, whether immunotherapy or a targeted drug may be useful.

Germline testing usually examines blood or saliva to determine whether a cancer-predisposition gene change was inherited and could also be relevant to relatives.

A tumour finding may affect treatment without being inherited.

An inherited genetic finding may affect the patient’s future cancer surveillance and may also have implications for children, siblings and other relatives.

Some young patients with colorectal cancer therefore need both types of assessment.

The Australian perspective

In Australia, mismatch-repair testing is an important part of colorectal cancer assessment, both for identifying patients who may benefit from immunotherapy and for recognising people who may require evaluation for Lynch syndrome. Current Australian eviQ guidance supports routine MMR screening of colorectal cancers and provides a pathway for interpreting MLH1/PMS2 loss.

For metastatic dMMR colorectal cancer, immunotherapy is now a major treatment pathway in Australia. Current eviQ guidance includes both pembrolizumab and nivolumab/ipilimumab pathways for eligible patients, with treatment choice depending on the individual clinical situation, current treatment indications and PBS eligibility at the time treatment is considered.

For cytoreductive surgery or HIPEC, I would want the case reviewed by a specialist multidisciplinary team with substantial experience in treating cancers that have spread to the lining of the abdomen and in performing these operations.

The diamond checklist: could HIPEC be suitable for me?

Before accepting or rejecting a major operation, I would want clear answers to questions such as:

• Is the cancer confined to the peritoneum or present elsewhere?
• What is the estimated PCI?
• Is the small bowel extensively involved?
• Can the surgical team realistically remove all visible cancer?
• Is the recommendation for cytoreductive surgery itself, HIPEC as well, or both?
• If HIPEC is proposed, which drug and protocol will be used?
• What evidence supports that particular HIPEC protocol?
• Has the case been reviewed by an experienced specialist multidisciplinary team?
• Is the cancer dMMR or MSI-high?
• Could systemic chemotherapy or immunotherapy be more appropriate before surgery?
• Has appropriate tumour and germline genetic assessment been completed?
• What are the centre’s rates of complete cytoreduction, major complications, bowel leakage and postoperative mortality?

The final question I would ask is:

“Which strategy gives this particular patient the best chance of meaningful long-term control—not simply the most aggressive treatment?”

The bottom line

HIPEC for colon cancer is not a general treatment for everyone with stage 4 disease involving the peritoneum.

For carefully selected patients with disease that can be completely removed, expert cytoreductive surgery may provide meaningful long-term disease control.

But PRODIGE 7 showed that adding the specific oxaliplatin-based HIPEC regimen tested in that trial did not improve median survival—41.7 versus 41.2 months—and increased serious complications by 60 days from about 15 in 100 to 26 in 100 patients.

That does not mean every form of HIPEC has been proven useless. Other regimens, particularly mitomycin-C-based approaches, continue to be considered by some specialist centres, but the evidence remains uncertain.

For a 42-year-old patient with MLH1 loss, there is another layer to the decision: could this be dMMR/MSI-high disease for which immunotherapy may be an important treatment option, and could the MLH1 finding indicate an inherited cancer predisposition?

Her lack of bowel symptoms did not prevent an advanced diagnosis.

Her lack of family history does not completely exclude an inherited genetic cause.

And the fact that HIPEC is technically possible does not automatically mean that it is the right treatment.

Key takeaways

• Cytoreductive surgery and HIPEC are different treatments, and not every patient with peritoneal spread will be suitable for them.
• The main goal is to remove all visible cancer where this is safely possible.
• In PRODIGE 7, adding oxaliplatin-based HIPEC did not improve survival and caused more serious complications.
• MLH1 loss may affect treatment because dMMR/MSI-high cancers can respond well to immunotherapy and may also raise the possibility of Lynch syndrome.

Key evidence

1. Quénet F, Elias D, Roca L, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256-266. doi:10.1016/S1470-2045(20)30599-4
2. Morris VK, Kennedy EB, Baxter NN, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2023;41(3):678-700. doi:10.1200/JCO.22.01690
3. Schultz KS, Bansal VV, Wach MM, et al. Consensus guideline for the management of colorectal cancer with peritoneal metastases. Ann Surg Oncol. 2026;33(6):5260-5282. doi:10.1245/s10434-025-17363-0
4. Hübner M, van Der Speeten K, Govaerts K, et al. 2022 Peritoneal Surface Oncology Group International consensus on HIPEC regimens for peritoneal malignancies: colorectal cancer. Ann Surg Oncol. 2024;31(1):567-576. doi:10.1245/s10434-023-14368-5
5. Mehta SS, Gelli M, Agarwal D, Goéré D. Complications of cytoreductive surgery and HIPEC in the treatment of peritoneal metastases. Indian J Surg Oncol. 2016;7(2):225-229. doi:10.1007/s13193-016-0504-6
6. André T, Elez E, Van Cutsem E, et al. Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer. N Engl J Med. 2024;391(21):2014-2026. doi:10.1056/NEJMoa2402141
7. eviQ. Mismatch repair (MMR)—genetic testing. Protocol 619. Accessed June 29, 2026. https://www.eviq.org.au/cancer-genetics/adult/genetic-testing-for-heritable-pathogenic-variants/619-mismatch-repair-mmr-genetic-testing

Frequently asked questions

1. Does having peritoneal metastases mean I should automatically have HIPEC?

No. The first question is whether you are a candidate for complete cytoreductive surgery. Whether HIPEC adds benefit depends on the cancer type and the specific HIPEC regimen being proposed.

2. Did PRODIGE 7 prove that HIPEC never works?

No. It showed that the specific short-duration oxaliplatin HIPEC regimen tested did not improve survival after successful cytoreductive surgery. It did not prove that every possible HIPEC drug or protocol is ineffective.

3. What is the PCI?

The Peritoneal Cancer Index is a way of estimating how much cancer is distributed throughout different regions of the abdomen. It helps surgeons judge whether complete removal may be feasible.

4. Does MLH1 loss mean I have Lynch syndrome?

Not necessarily. MLH1 can be lost because of changes that occurred only within the tumour. BRAF V600E and/or MLH1 promoter methylation testing can help determine whether inherited genetic testing is needed.

5. Could immunotherapy be more important than HIPEC?

In some patients, yes. If metastatic colorectal cancer is confirmed to be dMMR or MSI-high, immunotherapy can produce prolonged disease control and may significantly influence the treatment sequence.

About Dr Dilanka De Silva

Dr Dilanka De Silva is a Melbourne-based Medical Oncologist and Cancer Genetics Physician with experience in precision oncology, gastrointestinal cancer, hereditary cancer assessment and complex cancer second opinions.

He completed fellowship training at Memorial Sloan Kettering Cancer Center in New York and reviews Australian and international patients, including patients from Sri Lanka, the Maldives, Indonesia and the Philippines.

Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)