NEOADJUVANT CHEMOTHERAPY FOR ADVANCED OVARIAN CANCER

The adoption of neoadjuvant chemotherapy is associated with reduced mortality in women with advanced epithelial ovarian cancer, researchers report.

"There are gynecologic oncologists who believe that the increasing use of neoadjuvant chemotherapy in the United States may be harming patients,” Dr. Alexander Melamed from Massachusetts General Hospital, Boston, told Reuters Health by email. “Our study suggests a decline in the use of primary debulking surgery in favor of neoadjuvant chemotherapy resulted in improvement in both perioperative and long-term survival.”

“In two randomized trials, neoadjuvant chemotherapy followed by surgery was found to be noninferior in terms of long term survival compared with upfront surgery, but not superior,” he explained. “Furthermore, prior observational studies showed that patients selected to receive neoadjuvant chemotherapy have shorter survival than those selected to undergo primary surgery, although such studies cannot adequately account for baseline differences between patients due to strong selection.”

In the current quasi-experimental study, Dr. Melamed and colleagues used the U.S. National Cancer Database to assess whether greater utilization of neoadjuvant chemotherapy (NACT) is associated with better survival in advanced epithelial ovarian cancer.

They compared outcomes between two groups: women in New England and the “east south central” region (two areas where NACT use increased by 27% between 2011 and 2012) and control women in the south Atlantic, west north central, and east north central regions (where NACT use remained unchanged from 2011 to 2012).

The two groups did not differ significantly in age, race/ethnicity, stage, histologic type, grade, or comorbidities.

In the two regions with rapid adoption of NACT after 2011, all-cause mortality was 19% lower in 2012 than in 2011, whereas mortality did not change significantly in the other regions, according to the January 3 BMJ online report.

Similarly, Kaplan-Meier survival curves showed superior survival in New England and the east south central region after the abrupt increase in NACT use, whereas survival remained unchanged in the control regions.

Between 2011 and 2012, the proportion of women who died within 30 days after surgery declined from 3.1% to 1.8% in the rapidly adopting regions, whereas the proportion did not change significantly in the control regions.

During the same interval, 90-day postoperative mortality declined to a significantly greater extent in the rapidly adopting regions than in the control regions.

Moreover, the proportion of women who did not receive surgery and chemotherapy declined from 20.0% in 2011 to 17.4% in 2012 in the rapidly adopting regions, compared with a slight uptick from 19.0% to 19.5% in the control regions.

“Physicians should be reassured that using neoadjuvant chemotherapy for women with advanced ovarian cancer is unlikely to harm long-term outcomes,” Dr. Melamed said. “I hope that this finding will encourage providers to choose neoadjuvant chemotherapy for ovarian cancer patients who are unlikely to benefit from upfront surgery, like elderly patients, and those for whom resection of all visible disease is either not feasible or would require a very extensive surgical procedure.”

Dr. Alon Altman from the University of Manitoba, in Canada, who recently reviewed the selection criteria of neoadjuvant chemotherapy patients, told Reuters Health by email, "Patients that have advanced disease that cannot be adequately debulked to microscopic disease, or are too sick to undergo surgery, likely do better with NACT followed by interval surgery. Those patients that are healthy, and the surgeon believes that they can be optimally debulked, likely still have better outcomes from primary surgery. The balance is always morbidity and mortality.”

“The correct balance of NACT versus primary surgery is a difficult point to determine and is influenced by surgeon comfort, patient health/comorbidities, distance traveled, and wait times (especially in publicly funded systems),” he said. “For example, if you have to wait for 4 weeks, 6 weeks, 8 weeks for surgery, is NACT a better upfront option? Not sure we know the answer to this question, yet.”

“I think the two camps of oncologists will argue about these results,” Dr. Altman concluded. “The pro-NACT camp will support the study and say that there is good RCT (data) and now retrospective data that shows it is safe. The anti-NACT camp will likely say that there still exists a different in surgical ‘aggression’ and this difference may be present between these two centers.”

SOURCE: http://bit.ly/2AycqFI

BMJ 2018.