A mathematical tool may help to examine how doctors may coordinate available treatments for high-grade serous ovarian cancer. Published by Gu et al in the Proceedings of the National Academy of Sciences, the new analysis showed that patients who can have complete debulking surgery first, with chemotherapy added after (ie, primary debulking surgery), are more likely to have a superior outcome than patients treated with neoadjuvant chemotherapy.
Ovarian cancer is the eighth most common cancer and a major cause of cancer death in women worldwide; high-grade serous ovarian cancer constitutes roughly 70% of ovarian malignancies and carries the worst prognosis. Patients with the condition are typically treated with surgery and chemotherapy, but there has been long-standing controversy over the best order of treatment.
“The issue of whether primary debulking surgery or neoadjuvant chemotherapy should be used was highly controversial, and a major reason for it lies in the different characteristics of patients in different clinical studies,” said first study author Shengqing Gu, PhD, a graduate of the University of Toronto and now an instructor at Dana-Farber Cancer Institute. “We therefore built a mathematical model to simulate high-grade serous ovarian cancer clinical course, which allows us to compare treatment outcomes in the same virtual patients and examine which group of patients may respond differently to primary debulking surgery vs neoadjuvant chemotherapy.”
“Our model, combined with earlier clinical data, suggests that for patients who can undergo complete debulking, surgery offers the best chance of long-term survival—or even cure,” said study co–senior author Benjamin G. Neel, MD, PhD, Director of NYU Langone’s Perlmutter Cancer Center. “Our model also provides some insight about optimal early detection and treatment intervals.”
Our model, combined with earlier clinical data, suggests that for patients who can undergo complete debulking, surgery offers the best chance of long-term survival.... Our model also provides some insight about optimal early detection and treatment intervals.— Benjamin G. Neel, MD, PhD
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Study Details
The researchers used clinical data from roughly 300 patients in previous studies of responses to primary debulking surgery or neoadjuvant chemotherapy, taken from the Princess Margaret Cancer Center in Toronto and the Canadian Cancer Trials Group.
The researchers found that in patients who were well enough for surgery, debulking provided better results, because it has the best chance of removing cancer cells resistant to chemotherapy. For patients who are too ill for debulking surgery, the study suggests that a shorter period of initial chemotherapy, rather than the currently recommended interval, might provide a greater benefit.
The current analyses suggest several questions that future randomized clinical trials should examine, said the study authors. These include how much the influence of the time gap between surgery and subsequent chemotherapy may affect treatment outcome; whether there is a link between the number of initial chemotherapy cycles and outcomes; and whether complete secondary surgery on relapsed tumor improves prognosis.
“Our model shows that a fraction of patients can have long-term survival or even cure, but only when they undergo complete debulking, followed by the currently available therapies,” said Dr. Neel. “There is an urgent need for new therapies to provide cures for patients for whom complete debulking is not an option and for those with the most treatment-resistant cancer cells.”
Disclosure: This study was supported by the National Institutes of Health, the NIH Terry Fox Foundation, the Mary Kay Foundation, DCA Award from University of Toronto and Sara Elizabeth O’Brien Trust Fellowship, Ontario Ministry of Health and Long Term Care, and the Princess Margaret Cancer Foundation. For full disclosures of the study authors, visit pnas.org.
