OVARIAN CANCER that spreads to the lining of the abdominal cavity, called the peritoneum, is difficult to treat. Patients with this advanced cancer typically undergo debulking, also called cytoreductive surgery, a lengthy procedure in which surgeons aim to remove all cancer from the abdominal cavity and affected organs, including the ovaries and fallopian tubes as well as the bladder, colon and other parts of the gastrointestinal tract. In recent years, researchers have looked at the efficacy of using hyperthermic intraperitoneal chemotherapy (HIPEC), which is heated chemotherapy delivered directly to the peritoneum, to destroy remaining cancer cells immediately after debulking surgery.

Scientists in Belgium and the Netherlands published long-term data from OVHIPEC-1, a randomized phase III trial to evaluate adding HIPEC to interval cytoreductive surgery for ovarian cancer, in the October 2023 Lancet Oncology. (In interval surgery, chemotherapy is given to shrink the cancer prior to surgery.) The study enrolled 245 women with stage III epithelial ovarian cancer whose cancer showed no signs of progression after upfront chemotherapy. Researchers randomly assigned women to have debulking surgery alone, or surgery plus HIPEC using the chemotherapy drug cisplatin. After 10 years, median overall survival for the surgery-plus-HIPEC group was 44.9 months versus 33.3 months for the surgery group. Median progression-free survival was 14.3 months and 10.7 months, respectively. The rates of adverse events were similar—25% with surgery alone versus 27% with surgery plus HIPEC—and the most common events were abdominal pain, infection and slowed bowel function.

These results are in line with the researchers’ five-year analysis, published in the New England Journal of Medicine in 2018. In that analysis, 6.6% of patients in the surgery group had survived without progression at five years, compared with 12.3% in the surgery-plus-HIPEC group. At 10 years, 6.6% of the people who received surgery were alive with no progression versus 10.1% in the surgery-plus-HIPEC group. While surgery plus HIPEC did not result in better cure rates, the authors note that it significantly prolonged the time cancer was controlled. “The most important finding is that the benefit for patients with stage III ovarian carcinoma when interval cytoreductive surgery is combined with HIPEC remains present after a 10-year follow up,” says Willemien van Driel, lead author and a gynecologic oncologist at the Netherlands Cancer Institute in Amsterdam, who notes that patients in both arms of the study received similar treatment after subsequent recurrences.

Van Driel says that there is still variation in the use of HIPEC along with cytoreductive surgery. European guidelines published in October 2023 note that HIPEC with cytoreductive surgery should not be considered a standard of care. In the U.S., National Comprehensive Cancer Network guidelines state that HIPEC can be considered for patients with stage III epithelial ovarian cancer.

Van Driel and her colleagues are now enrolling patients in the OVHIPEC-2 trial, which will study the effect of adding HIPEC in women with stage III ovarian cancer undergoing primary surgery, which is surgery done upfront prior to chemotherapy. Other trials are evaluating HIPEC use for recurrent ovarian cancer. She notes there are several unanswered questions, including optimal dosing and temperature for HIPEC and the impact of including other drugs, such as PARP inhibitors, with this approach, since many of these drugs were not standard of care at the time of the trial.

Sharon Engel Robertson, a gynecologic oncologist at Indiana University Health Simon Cancer Center in Indianapolis who was not involved in the study, is most interested in the trial’s sub-analysis of BRCA-positive versus BRCA-negative patients, which suggests HIPEC may be more beneficial for those who do not carry a BRCA gene mutation. These people make up the majority of ovarian cancer patients, but they have fewer treatment options. “For BRCA-negative patients, we need something to move the numbers,” she says, noting that patients who carry the BRCA gene mutation often receive and respond to PARP inhibitors. In the study, people who did not have BRCA mutations but whose cancer tested positive for a feature called homologous recombination deficiency, meaning the lack of DNA repair ability, had the greatest benefit in median progression-free survival in this study: 17.7 months with surgery plus HIPEC versus 8.4 months with surgery alone. This finding could be useful in determining which patients are more likely to benefit from HIPEC, although van Driel notes more research is needed.

HIPEC may be a valid choice for patients who are generally healthy and open to a longer procedure and hospital stay. Although the length of surgery plus HIPEC varies, HIPEC generally adds 90 minutes or more to debulking surgery, which itself takes several hours. Also, patients typically require a longer hospital stay for recovery, possibly with intravenous or tube feedings while the digestive system recovers.