Invited commentary: Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy

In this issue, the group from the Sheba Medical Center, one of the most active and ambitious in the world, propose a very interesting set of results.1 The tittle of the paper is quite long but nevertheless informative: "Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy." Why such a proposal for a treatment option that is still much debated: cytoreductive surgery and HIPEC (CRS/HIPEC) for colon cancer peritoneal metastasis? Because as for any other surgical procedure which is an expensive process; because of the risk for the patient; because of the time devoted by the medical team, or because of its cost for the society. All the assumptions could be true, and for the simple reason, because all that is feasible is not always recommendable,2 if there is no benefit for the patient. The work published is a retrospective study but from a prospective consecutive cohort of patients operated recently and during the last 10 years. Authors divided the cohorts between those with low operative PCI (PCI 20). Results were obtained from the study of 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI 20. The median disease-free survival was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months) (p = 0.001 and p = 0.189, respectively) compared to an only chemotherapy strategy that had been reported at 16 months. These results could be considered as a validation of the proposed strategy: if a complete resection is possible, if the security of the patient is controlled, even with the HIPEC, oncological seem to exist and the exclusion of the CRS/HIPEC strategy using a cut-off proposed by some, with PCI, may not be a good strategy.3 The use of cytoreductive surgery and HIPEC had been so highly debated by many surgeons or medical oncologists who usually were not aware of the risk and results of the process. Their comments and reticence are nevertheless legitimate, since they are part of the medical healthcare team of the country. A first paper that was published in 2015 reported that in a single French cohort, when the extension of the disease, reported as the PCI, is highly elevated, it results in the decrease in OS.3 This concept is easy to understand and probably true; the more the carcinomatosis exists, the more difficult it is to control, and the rate of failure increases. However, the study includes patients operated many years ago with a selection process that is probably totally different today and with a high operative morbidity. The idea to select patients to offer a real chance of cure and to avoid unsuccessful cytoreduction is accepted by the vast majority of medical and surgical oncologists. But the decision is very difficult to make, because it has to be done before laparotomy. Regarding recent results, for some all colon carcinomatosis with MSI tumor need to receive in first line an immunotherapy without surgery,4 and for those with a PCI evaluated more than 15 need to receive only systemic chemotherapy.3 Biology or PCI, what is important, only one or both? The interest of the proposal of Sheba group lies in exploring if there is a cut off for the PCI ? Can you close the door to a possible surgical treatment, that if you control the morbidity and mortality, it can prolong the patient's life, regrading one simple number as PCI? The response is given in the title of the paper. Why such results? Probably, first because the postoperative morbidity is limited and offers to the patient a chance to have a normal postoperative course and so there is a chance for cure. Second, if we have to select the patient, we probably have to select a nontoxic HIPEC procedure that excludes Prodige 7 protocol and to select a good surgical team. First results that measure circulating tumor DNA (CtDNA), to select patients affected by a "general disease" with a high systemic CtDNA level versus others affected by a "locoregional disease" with a low or no CtDNA, may contribute to a more personalized oncological therapy and probably a better selection for the future. The results of the pioneering paper have not been confirmed, but technological progress and easy analysis should be done in the coming years.5 Other genomic analysis confirm that peritoneal site dissemination, in case of colon cancer, is associated with a specific genomic signature, as part of a family of colon cancer named CMS4, but with a more aggressive subtype related to polyclonal evolution that could explain resistance to chemotherapy.6 Specific biological evaluation could probably be used in the future to select cases that should receive a CRS/HIPEC strategy or that should be excluded from the procedure. If today genomic is not able to help us in our daily practice, selection of the patients have to be based on clinical experience of trained surgical teams and two rules have to be kept in mind: (1) complete cytoreductive surgery and (2) no postoperative mortality as proposed by the group from Sheba Medical Cancer, which is bound to be of help for the patients. Marc Pocard: Writing – original draft; writing – review & editing. The author declares no conflicts of interest.