Interval Cytoreductive Surgery After Chemo Boosts Survival in Stage IV Epithelial Ovarian Cancer

Interval cytoreductive surgery following neoadjuvant chemotherapy improved overall survival (OS) vs neoadjuvant chemotherapy alone in patients with initially unresectable stage IV ovarian cancer, according to data from a retrospective study presented in a poster at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

In this retrospective analysis, investigators collected data on 111 patients, including 30 (31%) who underwent primary debulking surgery, 65 (58.6%) who received neoadjuvant chemotherapy followed by interval cytoreductive surgery, and 16 (14%) who received neoadjuvant chemotherapy alone.

The median OS was 56 months for patients who underwent primary debulking surgery, 36.9 months for those given neoadjuvant chemotherapy and interval cytoreductive surgery, and 18.3 months for those who received neoadjuvant chemotherapy alone (P < .001). The median progression-free survival for the 3 groups was 27.8 months, 14.2 months, and 10.4 months, respectively (P < .001).

When comparing the 2 groups of patients who received neoadjuvant chemotherapy, a multivariant analysis controlling for stage and age showed that the OS benefit remained significant for interval cytoreductive surgery (HR, 0.24; 95%CI, 0.09-0.61; P = .003).

“Even if [patients with ovarian cancer] are not great candidates for primary debulking surgery, interval cytoreductive surgery is beneficial in terms of survival. We need to offer it to our patients, even if they require significant extensive surgical intervention at the time of interval cytoreductive surgery,” said lead study author Liat Hogen, MD, FRCSC. Hogen is an assistant professor in the Department of Obstetrics and Gynecology at the University of Toronto, and a gynecologic oncologist at Princess Margaret Cancer Centre in Toronto, Ontario, Canada.

In an interview with OncLive®, Hogen discussed the potential benefit for cytoreductive surgery in patients with initially unresectable stage IV epithelial ovarian cancer and the implications of findings from this retrospective analysis on future clinical decisions.

OncLive^®: Please discuss the rationale for conducting a study examining interval cytoreductive surgery in patients with initial unresectable stage IV ovarian cancer.

Hogen: Patients with ovarian cancer are typically known to be diagnosed at an advanced stage. Most patients are diagnosed at stage III, and some of them are at stage IV. [Approximately], 70% to 80% of patients will have advanced [disease] at diagnosis. When discussing treatment options, we aim to start with primary debulking surgery following neoadjuvant chemotherapy. However, some patients will not be amenable for this type of intervention and will need to go to neoadjuvant chemotherapy, usually followed by interval cytoreductive surgery, with the goal [of getting] to no visible residual disease, or at least to optimal [residual disease], which is less than 1 cm.

The challenge with some patients who have unresectable disease at presentation is that after you give neoadjuvant chemotherapy, there is still disease. It is unclear if you can resect it all at the time of interval cytoreductive surgery. This is where it’s important to characterize this population and see whether surgical intervention could benefit [these patients. This could help us] better understand the subpopulation in this category and which patients are likely to benefit from surgical intervention.

Could you expand on the factors that make patients with stage IVB epithelial ovarian cancer poor candidates for primary debulking surgery? What makes interval cytoreductive surgery a potentially more favorable approach vs neoadjuvant chemotherapy alone?

When looking at a patient at initial diagnosis, we look at [certain] factors to help us decide [between] primary cytoreductive surgery and neoadjuvant [chemotherapy]. One has to do with the disease distribution; if there are locations that are not amenable for surgical resection, such as brain metastases, bone metastases, multiple liver metastases, or intraparenchymal lung disease, those [patients] are not going to be amenable for surgical resection.

There are other factors, such as disease volume. If there are multiple areas [of disease] in the abdomen, chest, and retroperitoneum lymph nodes, that will entail a very large, extensive procedure, which may not be beneficial for the patient. Additionally, some patients present with a poor ECOG performance status of 2 or more. In those situations, an extensive surgical procedure might carry significant morbidity for these patients or, potentially, mortality.

Those are the criteria that we look at, and the same criteria go for interval cytoreductive surgery. However, after neoadjuvant chemotherapy, the volume of disease usually reduces, and sites of disease that were initially unresectable could potentially be resectable at that point. With chemotherapy, performance status could improve because of [a reduction in] disease burden.

Could you expand on the goal of the retrospective study presented at the 2023 SGO Annual Meeting on Women’s Cancer? What was examined? What were the key results?

We had 3 main objectives. One was to characterize this population, because this is a very heterogenous [disease], and to describe the sites of disease in those with stage IVB high-grade ovarian cancer. These data would then be compared between the patients who had surgery vs those who did not. We also aimed to compare survival between these 2 groups and to define the parameters that were associated with not offering surgical intervention to patients.

We had 111 patients who met eligibility criteria; [31%] had primary cytoreductive surgery who were included in the survival analysis but not in the analysis of comparing the prognosis between the [interval cytoreductive surgery and neoadjuvant chemotherapy alone] groups. This is because [patients who underwent primary debulking surgery] had the best prognosis of all groups regarding survival. Moreover, patients who had neoadjuvant [chemotherapy] and interval cytoreductive surgery [accounted for] 58.6% of the patients, and 14% had neoadjuvant chemotherapy and were found to not be candidates for interval cytoreductive surgery.

We compared the areas of diseases, and we found that most patients with stage IVB disease had intrathoracic disease in the form of metastatic lymph nodes in the chest. Some of them had enlarged groin lymph nodes that made [their disease] stage IVB, and a small proportion of patients had brain metastases, bone metastases, or intraparenchymal lung disease. A small proportion of patients also had intrasplenic disease or multiple liver lesions.

In regard to survival, patients who had primary debulking surgery had the best prognosis. Patients who had neoadjuvant chemotherapy plus interval cytoreductive surgery had a better prognosis than those who did not have surgical intervention. Most patients, even if they initially had unresectable stage IV disease, were found to have optimal [residual disease] after surgery, and most had no gross residual [disease] after interval cytoreductive surgery.

Factors that were associated with not proceeding to interval cytoreductive surgery were patients who were elderly and those who had liver parenchymal disease. In the multivariant analysis, interval cytoreductive surgery was found to be one of the most significant factors for survival benefit.

How could this analysis impact future treatment decisions in clinical practice?

We have a lot of information on prediction models about which patients should be taken to the operating room for primary cytoreductive surgery. However, we don’t know much about the patients who were not good candidates for primary debulking surgery, had neoadjuvant chemotherapy, had some response, but still have disease and will still require extensive surgical intervention to get them to no gross residual disease or optimal cytoreductive surgery.

We need to find different ways to better characterize these patients to determine who will benefit from surgery, such as building prediction models with better radiological assessments, using about biochemical markers, such as CA-125, or hormone recombination–deficient profiling for molecular analysis. Maybe using a machine-learning algorithm for those patients could help to select patients who will benefit from surgical intervention.

We talk a lot about hyperthermic intraperitoneal chemotherapy [HIPEC] for patients with stage III disease, but the main [phase 3] study [NCT00426257] did not include [patients with] stage IV [disease]. We do not know the role of HIPEC in patients with stage IV disease. Despite the fact that patients with stage IV disease [may] have metastatic lymph nodes in their chest or in the lung, the vast volume of disease is in the abdomen, and that is what eventually causes problems. There may be a role [for] HIPEC to those patients, and we’ll need to study this group more.

How would you approach patients who may not be candidates for interval cytoreductive surgery?

Most patients who we do not take to surgery are those with progressive disease, or their ECOG [performance status] worsened with chemotherapy. Those are the minority of patients. For them, it is unclear what the next step should be. Medical interventions could be the next steps for those patients.

Reference

Hogen L, Tanen A, May T, et al. Interval cytoreductive surgery in patients with initial unresectable stage IV ovarian cancer. Presented at 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, FL.