Chemotherapy Before Surgery Improves Outcomes in Advanced Ovarian Cancer

Despite clinical guidelines that advocate surgery as a first step, many patients with advanced ovarian cancer should be treated first with chemotherapy, a study by Columbia oncologists suggests.

The study found that women who are treated at cancer centers that commonly use chemotherapy first had greater short-term survival rates compared to centers that more commonly use surgery first. Women had the same likelihood of long-term survival at both centers.

“In light of the clinical trials and our new data, it’s time to consider a chemotherapy-first approach as the default to treating advanced ovarian cancer,” says lead author Alexander Melamed, MD, MPH, assistant professor of obstetrics & gynecology (in gynecologic oncology) at Columbia University Vagelos College of Physicians and Surgeons.

“Together, these findings should allay concerns that expanding the use of chemotherapy as a first-line treatment will harm patients, when in fact it might help them by reducing the extent and impact of surgery without affecting their long-term survival.”

The study was published online Sept. 30 in the journal JAMA Oncology.

For decades, “debulking” surgery has been the standard first-line treatment for advanced ovarian cancer, based on the idea that it is best to remove as much as the cancer as soon as possible before starting chemotherapy. The arduous procedure, which may involve operations to remove portions of the colon, the small intestine, or the entire spleen, in addition to the female reproductive organs, can cause significant morbidity and can increase the risk of early death.

In the early 2000s, some oncologists proposed using chemotherapy before surgery to lessen the magnitude of debulking surgery.

Despite four randomized clinical trials that favor a chemotherapy-first approach, national treatment guidelines and many prominent cancer experts continue to recommend surgery first for most patients with ovarian cancer that has spread within the abdomen.

One reason behind the discrepancy is that observational studies, which observe what happens to real-world patients, tend to support the surgery-first approach.

“But classic selection bias is a major factor in these studies,” Melamed says. “Oncologists tend to select the healthiest patients with the least disease for primary debulking surgery, while selecting the sickest patients with the most disease for neoadjuvant chemotherapy. So, when observational studies look at the outcomes, it appears that primary surgery is more effective.”

To help settle the debate, Melamed used a type of observational study that looks at differences in outcomes on a group level, rather than an individual level, to significantly reduce the impact of confounding introduced by selection bias.

The study examined data from nearly 40,000 patients treated in 664 cancer centers in the United States between 2004 and 2015. At the start of the study period, about 20% of patients with advanced ovarian cancerwere treated first with chemotherapy. By 2015, the chemotherapy-first approach doubled in about half of the centers and stayed the same in the other half.

When Melamed compared mortality rates between the two types of centers, he found that both types saw similar improvements in median overall survival, which increased to about three years. But the centers that increased use of the chemotherapy-first approach saw a significantly larger improvement in one-year mortality, which dropped by 6.5% compared to a drop of 3.1% in the other programs.

“It’s easy to hypothesize why patients who were treated first with chemotherapy had better short-term survival,” Melamed says. “They probably needed less complex surgery to remove their cancer, and therefore experienced fewer life-threatening complications. They were also probably more likely to recover from surgery and complete their chemotherapy.”

“Using chemotherapy first is not appropriate for all patients with ovarian cancer,” he adds. “But for many, it could have significant benefits and few, if any, drawbacks.”