Cytoreduction: What This Operation Is and Who It Suits in Peritoneal Carcinomatosis

What is cytoreduction?

It is an operation that aims to remove all visible tumor from the abdominal cavity, not just the largest deposit. The affected areas of the peritoneum, the inner lining of the abdominal cavity, are removed, along with the omentum, part of the bowel or other affected organs if needed. It is often combined with systemic chemotherapy before or after surgery, and with some tumors, with HIPEC. Whether chemotherapy is needed depends on the type of tumor: for example, after complete surgery for low-grade pseudomyxoma it is usually not given^[5].

Cytoreduction can be complete or incomplete. In a retrospective multicenter study of 506 patients with peritoneal carcinomatosis from colorectal cancer treated with cytoreduction plus intraperitoneal chemotherapy, complete cytoreduction was one of the independent factors associated with a better outcome^[2]. That is why radical surgery is planned when there is a real chance of removing all visible deposits.

What peritoneal carcinomatosis itself is, where it comes from and how it is investigated is described on the peritoneal carcinomatosis page.

What does PCI mean in a report?

The PCI, or peritoneal cancer index, shows how widespread carcinomatosis is. The abdominal cavity is divided into 13 regions, four of which cover the small bowel. In each region the largest deposit is scored: 0 for no visible tumor, 1 for up to 0.5 cm, 2 for more than 0.5 and up to 5 cm, and 3 for more than 5 cm or confluent disease. The total gives an index from 0 to 39^[1].

The PCI is not a percentage of involvement, and the same score in two people does not mean the same chance of surgery: it matters which regions are involved, especially the small bowel. There is no single cut-off beyond which surgery is impossible, and it depends on where the tumor comes from. For example, a large randomized trial in colorectal cancer enrolled patients with a PCI of 25 or less^[3]. That was an inclusion criterion for the trial, not a universal threshold.

The final PCI is determined by the surgeon during the operation by examining each region^[1]. The CT estimate is preliminary, so diagnostic laparoscopy is sometimes done before major surgery.

What do CC-0, CC-1 and so on mean?

CC is the completeness of cytoreduction score: how much tumor is left after surgery. At the end of the operation the surgeon assesses what remains^[1]:

• CC-0: no visible residual tumor;
• CC-1: residual nodules smaller than 2.5 mm;
• CC-2: residual disease from 2.5 mm to 2.5 cm;
• CC-3: residual disease larger than 2.5 cm or confluent deposits.

CC-0 means no tumor can be seen, but this does not yet mean that no microscopic cells remain. That is why follow-up after surgery is essential, and whether further treatment is needed is decided separately.

What is HIPEC, and is it always needed?

HIPEC is washing the abdominal cavity with a heated chemotherapy solution right after the tumor is removed. The idea is to act on microscopic residual disease that cannot be seen. But whether it helps depends on where the tumor comes from and which drug is used:

• colorectal cancer. The randomized PRODIGE 7 trial enrolled patients in whom all visible tumor was removed or residual disease was smaller than 1 mm, with systemic chemotherapy planned. Adding 30-minute oxaliplatin HIPEC gave no survival advantage, and there were more serious adverse events in the second month after surgery. The authors concluded that cytoreduction itself should be the cornerstone of treatment. The result applies to this specific HIPEC regimen^[3];
• ovarian cancer. The OVHIPEC trial enrolled patients with stage III epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had not progressed after three cycles of carboplatin and paclitaxel and in whom residual disease of no more than 10 mm was expected. Adding cisplatin HIPEC to interval cytoreduction lengthened the time to recurrence or death^[4]. This result cannot be applied to every ovarian cancer;
• pseudomyxoma. This is an accumulation of mucus in the abdominal cavity, most often from a tumor of the appendix. It ranges from slow-growing to aggressive. For selected patients who are candidates for surgery, the international guideline recommends complete cytoreduction with HIPEC^[5].

Whether you need HIPEC is decided by the tumor board. I perform operations with HIPEC together with a team. How the operation is done and what its risks are is described on the surgery for peritoneal carcinomatosis page.

Who may be a candidate for cytoreduction?

People in whom all visible tumor can be removed and whose health allows a major operation. The decision is based on several factors together, not on one:

• the extent of carcinomatosis, that is the PCI, small bowel involvement, and whether complete cytoreduction can be achieved;
• whether there are metastases outside the peritoneum, for example in the liver or lungs. Whether surgery is possible with limited metastases is decided individually;
• where the tumor comes from and how it responds to chemotherapy;
• general health and other illnesses.

In the retrospective study mentioned above, better outcomes were associated with complete cytoreduction, limited extent of carcinomatosis, age under 65 and chemotherapy after surgery, and worse outcomes with lymph node involvement, liver metastases and a poorly differentiated tumor^[2]. These are associations found in an observational study, not a prediction for an individual.

How risky is it?

Cytoreduction is a major operation, and the risks need to be discussed in advance. In PRODIGE 7, serious (grade 3 or higher) adverse events within a month of surgery occurred in 32% of patients after cytoreduction alone and 42% after cytoreduction with HIPEC. This difference was not statistically significant, while in the second month after surgery serious adverse events were more frequent after HIPEC: 26% versus 15%. Treatment-related deaths within a month occurred in 2% of patients in each group^[3]. These are data from selected trial participants, not a personal prediction.

That is why this operation is considered only when the expected benefit justifies the risk. If complete cytoreduction is not possible, the treatment plan depends on the tumor type: systemic treatment is considered, and if needed, procedures that relieve symptoms. After a response to chemotherapy, surgery sometimes becomes an option again.

What to ask your surgeon

1. What is the tumor source and the PCI?This determines whether cytoreduction is possible and whether HIPEC makes sense.
2. Is complete cytoreduction realistic?If not, ask what is offered instead and whether surgery might be reconsidered after chemotherapy.
3. Why HIPEC in your case?And with which drug: trial results differ between tumors and regimens.
4. Who makes the decision?It should be made by a tumor board after a full workup. Send your scans and reports: the online consultation is free.

Sources

1. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–374. PMID 8849962
2. Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–3292. PMID 15310771
3. 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. PMID 33476595
4. van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018;378(3):230–240. PMID 29342393
5. Govaerts K, Lurvink RJ, De Hingh IHJT, et al. Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment. Eur J Surg Oncol. 2021;47(1):11–35. PMID 32199769

This article is for general information and does not replace a consultation: whether surgery is possible is decided from your own scans, histology and the tumor board’s conclusion.