HIPEC for Gastric Cancer: Patient Selection, Recovery Insights, and Guideline Recommendations

Brian Badgwell, MD, MS, of The University of Texas MD Anderson Cancer Center, and Nataliya Uboha, MD, PhD, of University of Wisconsin School of Medicine and Public Health, discuss the hyperthermic intraperitoneal chemotherapy (HIPEC) procedure for managing gastric cancer, highlighting its use with cytoreduction to remove all peritoneal disease before adding heated chemotherapy.

Together, they weigh the importance of patient selection, response to systemic therapy, and recent trial data showing HIPEC does not significantly increase complications, while also touching on the potential benefits of intraperitoneal chemotherapy.

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Dr. Uboha: Could you tell us about the HIPEC procedure and the potential benefits of using HIPEC in managing patients with gastric cancer?

Dr. Badgwell: HIPEC gets a lot of attention partly because it is an easy abbreviation to remember, and it is a bit of a charged word because of that. However, it is only used in combination with cytoreduction, which involves removing all peritoneal disease. For gastric cancer, it is critical that all disease is removed. After that, chemotherapy is added directly into the peritoneum. Typically, we choose agents that work better with heat, so we add heat to enhance their effectiveness. That is the rationale behind HIPEC.

Dr. Uboha: You have done extensive research on this and even conducted your own prospective phase 2 trial on the role of HIPEC in gastric cancer patients, which was recently published with longer follow-up. You have shown that some patients really benefited from this treatment. What do you think are the most important factors that lead to the improvement in survival for these patients?

Dr. Badgwell: The first thing I will mention is that it is a select group of patients, and all the limitations of a single-arm phase 2 trial apply here. These were patients who had not progressed on first-line systemic therapy, or in a few cases, were already on second-line therapy. The most important predictor of their outcome was their response to systemic therapy. If they responded well to systemic therapy, it suggests that the disease outside of the peritoneum and within the peritoneum is controlled.

There is a common belief that chemotherapy does not work within the peritoneum due to the plasma-peritoneal barrier, but it does. I have seen it work in many laparoscopies. It is just that its effectiveness is limited, which is why intraperitoneal treatments like HIPEC make sense.

Dr. Uboha: Can you talk about the selection of your patients for this therapy based on the peritoneal index score and the extent of their disease? Does that play a role in your selection process?

Dr. Badgwell: Yes, absolutely. I have gone through a progression in my trials. In my first phase 2 trial, I did not combine gastrectomy with HIPEC; instead, I performed repeated HIPECs, and those patients had to show no imaging evidence of peritoneal disease. That was my strategy to keep the disease burden low. However, in the most recent trial you are referring to, I did not have a peritoneal carcinomatosis index (PCI) cutoff. I was able to select patients with a low PCI, but there was not a strict cutoff. Essentially, if I could see that I could remove all of their peritoneal disease with cytoreduction, they were candidates for the trial. Naturally, patients with a low PCI did better.

Dr. Uboha: That is exactly what you referred to earlier: complete cytoreduction is critical, as is the response to systemic therapy.

What is recovery like from HIPEC? How long do patients stay in the hospital, and when can they resume systemic therapy if needed?

Dr. Badgwell: In my most recent trial, which concluded around 2021, we were still learning, and patients tended to stay in the hospital for a long time with a significant morbidity rate. However, there have been a couple of newer trials, like the GASTRIPEC trial from Germany, which compared cytoreduction alone to cytoreduction plus HIPEC. They found no increase in complications with the addition of HIPEC. Another trial also compared gastrectomy alone to gastrectomy plus HIPEC and found no increase in complications with HIPEC. So, adding HIPEC does not appear to increase the complication rate significantly.

Typically, patients might stay in the hospital about a week longer if they experience complications. As with most perioperative trials, only about half of the patients are able to resume postoperative chemotherapy, usually around 6 to 8 weeks post-surgery, similar to those who undergo just gastrectomy.

Dr. Uboha: Patient selection is critical, and while you work with select patients in your practice, incorporating these therapies into standard treatments will still require appropriate patient selection.

Speaking of standard treatments, are there any guidelines on how to incorporate HIPEC into the treatment of patients with this disease?

Dr. Badgwell: Yes, surgeons have been working on this for a while. There is an international group and a U.S. group that have developed guidelines. Initially, this was coordinated through the University of Chicago, and now Dr. Kiran Turaga is updating these guidelines at Yale School of Medicine. These updated guidelines should be available soon.

Importantly, HIPEC has been included in the NCCN guidelines, which is a significant development for managing peritoneal disease in gastric cancer. However, it is important to note that these guidelines apply to a very select group of patients: those with peritoneal-only metastatic disease treated with systemic chemotherapy. The guidelines recommend 6 months of chemotherapy, though I prefer 4 months. Additionally, patients should have a PCI score of less than 10, with some studies suggesting less than 7.

Dr. Uboha: It is exciting to see these developments. I also work with metastatic gastroesophageal cancers, and patient selection is crucial. Patients who respond well to systemic therapy and have isolated metastatic disease can benefit from local regional therapies.

Switching gears a bit, can you compare intraperitoneal chemotherapy (IP chemo) to HIPEC? I know you are involved in research with IP chemo as well…

Dr. Badgwell: There is a common misconception that surgeons want to rush into surgery, but we recognize the importance of being selective, especially for patients with peritoneal disease. Surgery can significantly impact quality of life and increase complication rates. We are all looking for ways to manage peritoneal disease effectively before considering gastrectomy.

Normothermic, repeatable intraperitoneal paclitaxel is being studied extensively. Paclitaxel is effective in gastric cancer, stays in the peritoneum, and has seen a lot of use in Asia. There, they often use a port similar to a chest wall port, but slightly larger and placed in the abdomen, allowing for repeated administration of paclitaxel. There are different methods, such as peritoneal-only or bidirectional (systemic and intraperitoneal), and while it is still controversial, it makes theoretical sense. It is relatively safe, allows for high doses, is repeatable, and may help control peritoneal disease before subjecting patients to gastrectomy.

Dr. Uboha: And cytoreduction. This is great. Thank you so much for talking with me today. This has been very helpful, and I hope we will have more data to support more aggressive treatments for these patients.