Experts Debate Evidence For and Against HIPEC Use in CRC Peritoneal Disease

New York, New York— At the 2019 Great Debates and Updates in Gastrointestinal (GI) Malignancies meeting, Michael A. Choti, MD, GI Surgical Oncology, Hepatobiliary and Pancreatic Surgery, Banner Gateway Medical Center, Gilbert, Arizona, presented his arguments in support of the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of patients with colorectal cancer (CRC) peritoneal carcinomatosis.

Opposing Dr Choti was Andrea Cercek, MD, GI Oncology Service, Memorial Sloan Kettering Cancer Center, who presented evidence negating the use of HIPEC in this setting.

Citing decades of research on HIPEC therapy, he said that there’s been enthusiasm for this approach being used in CRC for some time. However, data specific to this subset of patients is admittedly lacking.

Describing peritoneal carcinomatosis in metastatic CRC as rare and difficult to measure, Dr Choti said that although chemotherapy has demonstrated positive outcomes in CRC, outcomes in this subgroup remain unsteady.

“We’re really debating systemic therapy versus cytoreductive surgery with the intraperitoneal chemotherapy, which can be delivered 2 ways,” he explained.

“Either with an open approach, bathing the abdominal cavity with chemotherapy during surgery, or a closed-circuit approach—both approaches are used similarly,” he added.

Currently, volume and symptoms are considered when deciding whether HIPEC is the right treatment for patients with peritoneal carcinomatosis in metastatic CRC.

“Just like in systemic therapies, we don’t really have good data on what the optimal strategy is, but there are some studies to show that in [patients with] low-volume disease, the drug penetrates,” Dr Choti said.

In a 2008 study by Verwaal et al, HIPEC led to exceptional outcomes in patients with peritoneal disease compared with F-5U/leucovorin chemotherapy.

Another study, Prodige 7, which was conducted by Quenet et al and presented at ASCO 2018, yielded controversy and “brought some relative negative enthusiasm to the role of HIPEC for CRC,” according to Dr Choti. Patients in both arms in the study had cytoreductive surgery, but only 50% were randomized to receive HIPEC.

“What was remarkable about this is the median survival in both arms was 40 months,” he said, adding that there were no differences in complications between both patient groups.

In addition, Dr Choti described how HIPEC was shown to improve outcomes in a separate study of patients with ovarian cancer.

“There’s clearly a signal that there’s a real role for this approach in malignancies within the abdominal cavity,” he said, adding that operative times and morbidity have decreased since implementation of HIPEC. “It’s a therapy that is tolerated much better than in the past where this was often a concern.”

In her counter-response to Dr Choti, Dr Cercek opened by agreeing with her debate partner in that peritoneal disease is very uncommon and rife with poor outcomes.

But this is where the acquiescence waned.

“The point of intraperitoneal chemotherapy is to really try to eliminate any microscopic residual disease that’s remaining in the abdomen,” Dr Cercek told listeners.

“[HIPEC] is not really supported by data at all,” she continued, adding that the therapy is not included in national guidelines for treating CRC, and that while it remains an experimental therapy, it should be considered as such.

According to Dr Cercek, the level of evidence supportive the use of HIPEC is severely lacking, or riddled with holes.

Citing a Dutch therapy of patients receiving HIPEC, she pointed out the lack of patients involved in the study and the high rate of participants ineligible for surgery due to severe disease.

“Ultimately we were left with very, very small numbers that did give us some positive data but have to be interpreted with a grain of salt,” Dr Cercek said. “And the really important take-home point here, I think, is that if you break it down and you look at the patients who achieved complete cytoreductive surgeries (ie, patients where all visible tumor was removed), their survival was phenomenal.”

Of note, patients who had residual disease did “significantly worse” than was expected.

Findings from several other comparative studies also supported Dr Cercek’s argument, and led her to ask whether HIPEC really contributes to patient outcomes, or if benefit is achieved with chemotherapy alone.

“Is it just that we achieved the benefit that we achieved with surgery, and the intraperitoneal chemotherapy really just adds morbidity?” she asked attendees.

In her concluding remarks, Dr Cercek reiterated that there is a lack of evidence overall and specifically from the first large, randomized clinical trial of patients with CRC and peritoneal disease that support the addition of HIPEC to their therapy regimen.—Hina Khaliq