Surgery Remains Standard of Care in Advanced Ovarian Cancer

Amer Karam, MD

Neoadjuvant chemotherapy has emerged as a potential treatment approach for patients with advanced-stage ovarian cancer, though primary debulking surgery remains the standard of care for those who are eligible, said Amer Karam, MD.

“In our division at Stanford Medicine, we believe that primary debulking surgery or upfront surgery should be the standard of care for those patients who can undergo surgery [with the goal of achieving] minimal residual disease (MRD),” he said.

Although neoadjuvant chemotherapy is believed to reduce the burden of disease in patients who are too ill or frail to undergo upfront surgery, there are no robust data to prove the superiority of the regimen.

Therefore, physicians are awaiting the results of the ongoing TRUST trial, which is investigating the use of radical upfront surgery versus neoadjuvant chemotherapy in patients with advanced-stage disease (NCT02828618). Patients in the comparator arm will receive primary debulking surgery followed by 6 cycles of standard chemotherapy, whereas those in the experimental arm will receive 3 cycles of standard neoadjuvant chemotherapy followed by interval debulking surgery and another 3 cycles of standard chemotherapy. The study has an estimated completion date of April 2023.

OncLive: Could you discuss the current surgical approaches used for the treatment of patients with ovarian cancer?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer, Karam, associate clinical professor of Gynecologic Oncology at Stanford Hospital and director of Robotic Surgery and Outreach in the Division of Gynecologic Oncology at Stanford Medicine, discussed surgical options for patients with advanced-stage ovarian cancer and the emergence of neoadjuvant chemotherapy.Karam: For almost a century now, the concept of surgery for advanced-stage ovarian cancer focused on surgical debulking or cytoreduction; moreover, the concept of leaving as little as possible in terms of residual disease. Our goal was to be able to remove as much as possible of the cancer. Over the years, more radical techniques, particularly ultra-radical surgery in the upper abdomen, have been used to do that.

Is MRD commonly achieved after surgery?

Is neoadjuvant chemotherapy widely accepted?

How many patients receive neoadjuvant chemotherapy?

Where does interval cytoreduction fit into the paradigm?

The other concept that has started to come forward is neoadjuvant chemotherapy. Patients who are too ill or have an overwhelming burden of disease are given neoadjuvant chemotherapy in order to reduce their disease burden; [this] allows them to heal and get stronger before they undergo surgery to remove the cancer from their abdomen. We would like to leave our patients with optimal results, which would be less than 1 cm of residual disease. We leave over 75% of our patients with less than 1 cm of disease. For those patients who did not go through primary debulking surgery, our goal of no residual disease or MRD is over 50%. Patients who cannot go through upfront debulking surgery, those who are too ill or frail, or those who have disease that is too overwhelming, should be offered neoadjuvant chemotherapy. However, we strive to offer upfront surgery to all of our patients, if possible. About one-third of our patients get neoadjuvant chemotherapy because of their disease status. At the time of diagnostic laparoscopy, these patients had a disease burden that [indicated] that they would not be good candidates for primary debulking surgery. Interval debulking surgery is part of the treatment paradigm for the majority of patients who undergo neoadjuvant chemotherapy. Not every single patient who gets neoadjuvant chemotherapy will get to interval debulking surgery. Unfortunately, some patients progress, and some patients have disease burden that's still very significant at the time of interval debulking surgery, [rendering them ineligible for] an optimal interval debulking surgery.

What is the treatment for those who progress through neoadjuvant chemotherapy?

Where do you see the biggest application of laparoscopy? How is this operation used in patients with borderline tumors?

The results from our own internal data as well as from clinical trials show that interval debulking surgery is a much less morbid operation than that of primary debulking surgery. Fewer patients require [transfer] to the intensive care unit, blood transfusions, and blood component transfusions. Patients also have a lower risk of requiring bowel surgery or ultra-radical procedures such as splenectomies, hepatectomies, and diaphragm resections. Unfortunately, all of our data point toward a poor outcome for those patients who progress on neoadjuvant chemotherapy. These patients invariably become platinum-refractory and progress through the lines of salvage chemotherapy we have to offer them. We try the best we can to salvage these patients by offering them opportunities outside of traditional chemotherapy, whether it’s on clinical trial or with other chemotherapy regimens.Any patient who comes in with advanced-stage ovarian cancer should be offered laparoscopy as a way to triage them in terms of primary debulking surgery. I offer it to all of my patients who are going to have primary debulking surgery; it's something that I apply universally to all of my patients. Borderline tumors are an interesting entity. The rate of advanced-stage borderline tumors is lower than we would expect in high-grade ovarian cancer.

What are your main takeaways for fellow oncologists working in this space?

[Laparoscopy is] much more likely to find early-stage disease with borderline tumors. In the event of a borderline tumor, diagnostic laparoscopy is still useful. There are instances where borderline tumors are spread so far inside the abdomen that surgery would not be able to resect all of the disease. Still, for these patients, surgery probably plays a different role than what you would see in high-grade serous ovarian cancer. There may be a role for surgical debulking even if you don't leave patients with MRD. It's important to convey that the only way for us to treat patients adequately and offer them the best possible options is to gather as much robust data as possible. I applaud my colleagues’ efforts to put together randomized controlled trials to try to answer some of these surgical questions. A lot of our treatment decisions were based on historical data that are, unfortunately, in many cases, incomplete or of lower quality in terms of their scientific validity.

I'm looking forward to seeing the results of the TRUST trial, which is examining radical upfront surgery therapy for ovarian cancer. It's a multicenter, multinational trial that is comparing the use of primary debulking surgery with neoadjuvant chemotherapy. [Hopefully], it will help settle the debate of whether or not primary debulking surgery should be the standard of care.