Surgery Still Mainstay in Advanced Ovarian Cancer

Mario M. Leitao, Jr, MD, FACOG, FACS

Surgery is still considered a vital part of initial therapy for patients with advanced ovarian cancer, but the current debate is the timing of the procedure as well as the role of neoadjuvant chemotherapy, said Mario M. Leitao, Jr, MD, FACOG, FACS.

There are certain factors to take into consideration when deciding which patients should undergo upfront surgery or neoadjuvant chemotherapy, said Leitao, who is fellowship director, Gynecology Service, director, Minimal Access and Robotic Surgery Program, Department of Surgery at Memorial Sloan Kettering Cancer Center. For example, if an elderly patient has widespread metastatic disease, they would likely benefit from neoadjuvant chemotherapy with a platinum-based agent and paclitaxel. Occasionally, the regimen can include the antiangiogenic agent bevacizumab (Avastin), Leitao adds.

“Surgery is a type of treatment—a lot of folks tend to forget that it is,” said Leitao. “But it is only one aspect of treatment, so we also have to make sure that our patients are living longer with a good quality of life.”

OncLive^®: How do you use patient selection to determine whether a patient should get upfront surgery or neoadjuvant chemotherapy?

In an interview at the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer and Soft Tissue Sarcoma, Leitao highlighted the decision-making process for the placement of surgery in patients with newly diagnosed advanced ovarian cancer, as well as the use of hyperthermic intraperitoneal chemotherapy (HIPEC).Leitao: At our institution, we still take a primary debulking approach. There is a flowchart that we kind of use in our head to decide who should receive surgery. There are a few criteria that would lead us to doing neoadjuvant chemotherapy first; it is usually in patients who are older—more than 70 years old—who have widespread metastatic disease and who have a less-than-optimal performance status or low albumin. If a patient meets these 3 criteria, those patients are primarily offered neoadjuvant chemotherapy first. If they don't meet those criteria, we will look at the disease distribution at the CT scan. There are some instances where we see that a complete cytoreduction is not possible on a CT scan. That is somewhat surgeon dependent.

What about interval debulking?

What are you doing in terms of triaging patients?

Also, we make sure the patient is medically fit for surgery. Therefore, for a patient who is sick or who has had a recent pulmonary embolism—someone who we don't think will be able undergo a full surgical resection—we will often offer them neoadjuvant chemotherapy first. Everyone else is a candidate for primary debulking.Interval debulking is essentially what would happen for someone who undergoes neoadjuvant chemotherapy. Surgery is still considered an important part of initial therapy for patients, although the debate is now about the timing of the surgery. Is it before the chemotherapy or after 3 cycles of chemotherapy? All patients will have some surgery at some point, but unfortunately, there are some patients who will never get to surgery either because they are too sick, too old, or they don't have a good response to initial therapy.We don't use any sort of laparoscopic scoring system. We currently have a Memorial Sloan Kettering Cancer Center—specific scoring system based on prospective studies that we did in conjunction with The University of Texas MD Anderson Cancer Center, which looks at certain patient factors and key elements of a CT scan finding. We have radiologists who are just specialized in looking at these CT scans and we look at them ourselves. Certain elements are given a certain score, and then there is a score created for this using patient age, American Society of Anesthesiologists score, and a few CT scan features that we've found to be predictive of a complete cytoreduction.

Is there a preferred agent for neoadjuvant chemotherapy?

If a patient is eligible for both upfront surgery and neoadjuvant chemotherapy, what would be the deciding factor?

Based on that score, we'll decide what to do primarily. If it's a low score, it means we have a very high chance at least in doing an optimal or complete cytoreduction. We will take those patients right to a laparotomy. If they have a higher score, our chances of an optimal or complete cytoreduction are reduced but are still relatively good. For those patients, we will start with a laparoscopic assessment and make a determination if we can achieve a complete resection.There is some controversy in this area. There is always a platinum/paclitaxel backbone. Often, bevacizumab is added to the regimen, and that is based on certain patient factors. If the patients have high disease burden and are symptomatic, sometimes we will add bevacizumab. Generally speaking, we avoid bevacizumab since we are planning to do surgery. Using the platinum/paclitaxel backbone, we do prefer to go with the weekly regimen rather than giving it every 3 weeks.We favor primary debulking, so if they are a candidate for primary debulking off-trial, that is our preference. We would sort of encourage that in our patients, although we always encourage second and third opinions, too. From our interpretation of the literature, we feel that primary debulking is in the best interest of the patient, at least in our hands. We are participating in an international randomized study called the TRUST study. Any patient who is eligible for surgery is being offered participation in that trial, which is actually nearing completion; they have enrolled over 700 patients internationally. Surgical trials are very hard to ensure quality; surgery is not quite the same as basic treatment. Surgical technique and surgeon skill are highly variable.

What the TRUST investigators have done is initially only allowed certain surgeons in certain institutions to enroll patients. They actually went out, visited every institution, and observed them operating before viewing their records and outcomes for a certain number of months. Every institution had a benchmark of optimal and complete cytoreductive resection rates. They were given a letter score, and if you had a certain score, you were able to enroll patients. It's a huge effort by the investigators, but it's a tremendous effort that will hopefully ensure better quality surgery.

Could you highlight the use of HIPEC and lymphadenectomy?

There is also a requirement in this study that enrolled institutions to track every eligible patient as well as which ones are offered the protocol. This is important because in most clinical trials, we don't know how participants go about preselection.For a while, folks were doing routine lymphadenectomies after complete resection in the abdomen—this is removing normal-appearing lymph nodes in the pelvic area up to the renal vessels. To me, it never made sense because the abdominal area goes way above the renal vessels. This is in patients with non-enlarged lymph nodes. If they are enlarged, then the goal is to debulk them also, and that's different.

There was a recently published trial that randomized patients at the end of their optimal cytoreduction to either a lymphadenectomy or not. The progression-free survival (PFS) and overall survival (OS) are exactly the same, so there is not even a suggestion that there was any benefit. To me, that's not surprising because I never thought that would be of value to patients.

For the interval debulking and HIPEC story, this is kind of the new thing with a lot of rave surrounding it. Unfortunately, we have little level 1 evidence to support its use. Investigators in The Netherlands did a randomized trial in patients receiving neoadjuvant chemotherapy and undergoing interval debulking surgery; they were randomized to undergo HIPEC or not and then getting systemic therapy. Results showed a significant improvement in both PFS and OS. That's the only randomized trial in this setting, so it's something we should pay attention to. It would not be unreasonable if you can offer HIPEC at the time of interval debulking. We don't know the role of HIPEC in other settings, such as upfront.