Debate Continues Between Upfront Surgery and Neoadjuvant Chemo in Advanced Ovarian Cancer

R. Wendel Naumann, MD

Primary debulking surgery is standard for patients with newly diagnosed advanced ovarian cancer, but for those who are not candidates for the procedure, neoadjuvant chemotherapy and interval debulking surgery can be used without sacrificing outcomes, said R. Wendel Naumann, MD.

“We know surgery is important in ovarian cancer, but there has been a paradigm shift from only doing surgery in the upfront setting to using neoadjuvant chemotherapy and interval cytoreductive surgery,” said Naumann. “We know [neoadjuvant chemotherapy] decreases morbidity. Now, we have 4 randomized studies—3 noninferiority studies and 1 superiority study—that suggest that the oncologic outcomes regarding progression-free survival and overall survival are similar, and the morbidity from the surgery is much less.”

Although the decision of whether to pursue primary debulking surgery versus neoadjuvant chemotherapy should be done in a multidisciplinary setting, patients who are better suited for surgery are generally those who are symptomatic and require immediate treatment. Conversely, patients with advanced disease and large-volume ascites may benefit more from neoadjuvant chemotherapy, explained Naumann.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Naumann, director of Minimally Invasive Surgery in Gynecologic Oncology at Carolinas Medical Center, Atrium Health, discussed the criteria for primary debulking versus neoadjuvant chemotherapy in patients with advanced ovarian cancer.

OncLive^®: Could you discuss the utility of neoadjuvant chemotherapy in a setting that has predominantly been led by surgery?

Naumann: The thing that we forget is that much of the outcome is based on a patient’s disease burden as well as the surgical complexity. The benefit that we get from these very aggressive debulking procedures is probably less than we think.

Even if we get patients who have a high disease burden down to R0, they probably won't have the outcome we think they will. There is a relatively high mortality associated with aggressive upfront surgery that ranges from 5% to 8%. We have to make a decision in determining who is a good candidate for upfront surgery versus who is a good candidate for neoadjuvant chemotherapy. Importantly, we don't lose anything by giving chemotherapy first and then operating later. That also opens up the possibility of more patients having a complete response (CR). In the initial study that Ignace Vergote, MD, PhD, of Catholic University Leuven and Cancer Institute at University Hospitals, and colleagues conducted in 2010, there was about a 5% CR rate. In patients who have BRCA mutations, the CR rate can be as high as 25%. To me, those patients can undergo minimally invasive surgery for debulking if they have a good response rate [to neoadjuvant chemotherapy].

What are some of the patient criteria for primary debulking surgery?

It’s a great question. Patients who are the best candidates for primary surgery are symptomatic, have very large masses, and may have a partial bowel obstruction; these patients require immediate attention. They can’t go through neoadjuvant chemotherapy and wait the 3 to 6 weeks for the chemotherapy to kick in. On the other hand of the spectrum, there are patients who have very advanced disease, stage IV disease, and upper abdominal disease with large-volume ascites; these patients are good candidates for neoadjuvant therapy. Once you’ve given the chemotherapy, you've reduced their surgical complexity and their need for ultraradical and upper abdominal procedures, which then reduces the morbidity of surgery.

What advice would you give your colleagues regarding this decision?

It is important that all patients are seen by a gynecologic oncologist upfront to help make this determination. This [process] could be done jointly because there are going to be patients who benefit from neoadjuvant chemotherapy or upfront surgery and that [decision] should be determined by a multidisciplinary team.

The main message is that if you do neoadjuvant chemotherapy, you do not compromise a patient oncologic outcomes. Furthermore, you can potentially make the surgery less morbid. However, the decision to do neoadjuvant chemotherapy versus primary surgery is a difficult decision that again, needs to be made by a multidisciplinary team.

Where do you see the role of surgery headed in the future?

I hope we can get better upfront neoadjuvant chemotherapy that would allow for less aggressive surgery. It would be nice if we did not have to do super radical surgery on patients with ovarian cancer. We have moved toward minimally invasive surgery in our institution and have shown that this is a reasonable strategy for many patients. Over 80% of patients can undergo minimally invasive surgery as opposed to open surgery; this allows them to not only have less morbidity but they are able to get back on their chemotherapy sooner as well.