Debulking Advanced Ovarian Cancer To Low Volume Linked With Better Survival

There is a survival benefit to debulking stage IIIC ovarian, fallopian tube, and peritoneal tumors down to 10mm or smaller in size, a single-center retrospective study demonstrated.

“You shouldn’t just relegate those patients [in whom] you can’t get a complete gross resection to neoadjuvant chemotherapy, because their median survival is going to generally be around 30-36 months,” Dr. Dennis S. Chi said in an interview in advance of the annual meeting of Society of Gynecologic Oncology. “But if you do a primary debulking and you get the volume of residual disease down to 10 mm or smaller in maximal diameter, the median survivals can be in the mid-40s to over 80 months.”

Dr. Dennis S. Chi

Dr. Chi, head of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center, New York, said that the current findings come at a time when the initial management of advanced ovarian cancer is in flux and is controversial. “For decades it used to be that the initial step was to do an operation and to do a primary debulking surgery,” he said. “But studies in the 1980s and 1990s showed that if you did primary debulking surgery and you did the standard surgery that gynecologic oncologists did at that time, greater than 50% of the time you would not do an operation that would result in an optimal debulking, where you get all or almost all of the visible cancer out.”

Two camps formed, he continued, one consisting of clinicians who believe “we need to do better surgery, or more comprehensive surgery,” and another group of clinicians who say, “Why don’t we treat with chemotherapy first for three treatments, and then do surgery? Maybe this will shrink the cancer and consequently improve the surgical outcome.’ Both camps agree that if you cannot get all the cancer out or almost all the cancer out, then you should start with chemotherapy first. The question then lies, what is the cut-off?”

In a study led by Dr. Chi and Dr. Vasileios Sioulas, the Senior International Gynecologic Oncology Fellow at Memorial Sloan Kettering Cancer Center, the authors set out to explore the effect of primary cytoreduction to minimal but gross residual disease in women with bulky stage IIIC ovarian/fallopian tube/primary peritoneal cancer. They retrospectively evaluated the records of 496 women who underwent primary debulking surgery at the cancer center between 2001 and 2010. Their median age was 62 years, the median operative time was 265 minutes, and 46% of the patients received at least one cycle of primary or consolidation intraperitoneal chemotherapy.

The researchers assigned patients to one of four groups based on reported gross residual disease. More than one-third (37%) had no gross residual disease (group 1); 26% had residual disease of 1-5 mm in diameter (group 2); 11% had residual disease of 6-10 mm in diameter (group 3), and 26% had residual disease that exceeded 10 mm in diameter (group 4). The median follow-up in the entire cohort was 53 months, the median progression-free survival was 18.6 months, and the median overall survival was 54.7 months. However, median progression-free survival and median overall survival varied significantly among the four assigned groups. It was 26.7 months for group 1, 20.7 months for group 2, 16.2 months for group 3, and 13.6 months for group 4 (P less than .001). At the same time, median overall survival was 83.4 months for group 1, 54.5 months for 2, 43.8 months for group 3, and 38.9 months for group 4 (P less than .001).

Dr. Vasileios SioulasTo be consistent with the vast majority of the existing literature, which used the cut-off of 10 mm to define optimal residual disease, Dr. Sioulas and his associates merged patients with residual disease 1-5 mm and 6-10 mm into one group and found that its median overall survival was 52.6 months. Patients with residual disease of 1-10 mm had significantly better overall survival, as compared to those with residual disease greater than 10 mm (P less than .001). Importantly, among the patients with residual disease of 1-10 mm, the administration of at least one cycle of primary intraperitoneal chemotherapy was associated with significantly prolonged overall survival, as compared to the sole use of intravenous chemotherapy. The median overall survival for those groups was 65.1 and 40.6 months, respectively (P = .002).

“I certainly believe neoadjuvant chemotherapy is the best approach in certain situations, but I don’t think it should be the knee-jerk reflex for all patients with advanced ovarian cancer,” Dr. Chi said. “I think that may be doing a disservice to many patients who could get a distinct prolongation of life and overall survival, or even cure, with a primary debulking surgery approach.”

He noted that ovarian cancer “goes where it wants to go. It doesn’t care what the training or surgical capabilities of the surgeon are. It’s going to go where it wants to go, so you can’t make the patient and the disease fit into your training skill set. You have to adapt your training skill set to the disease.”

The ideal study of this issue, Dr. Chi said, would “compare 400 or 500 patients with primary debulking and 400 or 500 patients who receive neoadjuvant chemotherapy to see which approach is better. There are two trials that have been done in Europe and have shown that it doesn’t matter, that the outcomes are the same whether you do primary debulking first or neoadjuvant chemotherapy first [see N. Engl. J. Med. 2010;363;943-53 and Lancet 2015;386:249-57]. Unfortunately, the survival outcomes in their primary debulking surgery arm were much lower as compared to other studies, especially those conducted in the United States. This highlights the importance of homogeneity in advanced surgical skills as a prerequisite before we draw definite conclusions about the survival outcomes after primary debulking surgery in patients with advanced disease.”

Dr. Chi acknowledged certain limitations of the study, including its retrospective design and the fact that surgeons at Memorial Sloan Kettering “are more willing, and have more support staff available, to perform comprehensive surgeries than at other centers.”

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