NCCN OVARIAN CANCER GUIDELINES

March 20, 2012 (Hollywood, Florida) — The ovarian cancer guidelines from the National Comprehensive Cancer Network (NCCN) address a number of ongoing controversies, according to a presenter here at the NCCN 17th Annual Conference.

"There have not been a lot of changes in the past year, but there are various areas of controversy in the guidelines," Robert Morgan, MD, from the City of Hope Comprehensive Cancer Center in Los Angeles, California, told Medscape Medical News at the conference.

One such controversy is about the usefulness of the biomarker CA-125 to monitor patients who have been treated with surgery and/or chemotherapy. Dr. Morgan called CA-125 the "most controversial" aspect of patient follow-up.

The follow-up guidance calls for patient visits every 2 to 4 months for 2 years, every 3 to 4 months for 3 years, and annually after that. At all of these visits, CA-125 and other tumor markers should be checked if "initially elevated," according to the guideline.

The guidelines offer clinicians 2 different routes to take in the event of rising CA-125 (biochemical recurrence) during follow-up — after imaging studies, one can either undertake immediate treatment for recurrent disease or delay treatment until clinical relapse.

Dr. Morgan noted that a European randomized trial compared outcomes with these 2 options (Lancet. 2010;376:1155-1163). That trial confirmed that CA-125 can reliably detect asymptomatic relapsing ovarian cancer.

However, it also showed that women with relapsed ovarian cancer did not live longer if chemotherapy was started earlier on the basis of a rising CA-125 level, as opposed to delaying treatment until symptoms developed. They also had a diminished quality of life because of chemotherapy.

The lead author of the European trial, Gordon Rustin, MD, has said, in effect, "don't follow CA-125 at all," Dr. Morgan explained. But that mentality denies patients and their clinicians the choice of using the marker, he said.

"Most of my patients...really want me to follow the CA-125," said Dr. Morgan.

The subject continues to be very timely, noted Dr. Morgan. He told the NCCN audience that just last week,Medscape Hematology-Oncology published a debate on CA-125 between Dr. Rustin, who is from the Mount Vernon Cancer Centre in Northwood, United Kingdom, and another ovarian cancer expert, Beth Karlan, MD, from the Samuel Oschin Comprehensive Cancer Institute in Los Angeles, California.

The NCCN and the Society of Gynecologic Oncologists suggest discussing the possible utility of CA-125 with patients, said Dr. Morgan.

In defense of that guidance, Dr. Morgan pointed out that the European trial — and its negative findings about survival — had multiple limitations. The trial did not address the possible role of secondary cytoreduction in recurrent cases, participants were not stratified for residual disease after cytoreduction, remission was not consistently confirmed by imaging, and treatment regimens at relapse were not standardized.

Neoadjuvant Chemotherapy for Some Patients

In one of the few notable changes in the ovarian cancer guidelines, the NCCN has upgraded to category 1 (from 2A) their recommendation to consider neoadjuvant chemotherapy in some patients, said Carolyn Johnston, MD, from the University of Michigan Comprehensive Cancer Center in Ann Arbor.

Specifically, neoadjuvant chemotherapy is recommended for patients with bulky stage III/IV disease who are determined "not to be surgical candidates," reads the guideline. Primary interval cytoreduction is also recommended as part of this guidance.

"How do we select patients who are candidates for neoadjuvant therapy?" Dr. Johnston asked rhetorically. First of all, the decision should be made by a gynecologic oncologist, she answered.

In general, these patients "have too much bulk for surgery" or the morbidity of debulking precludes the upfront surgery, she told the NCCN audience.

Dr. Morgan explained that the approach of giving chemotherapy before surgery to these types of patients is not as well accepted in the United States as it is in Europe. Therefore, this recommendation is another area of controversy in the NCCN ovarian cancer guidelines.

"Work needs to be done" to clarify and predict which patients will have incomplete cytoreduction, Dr. Johnston added. But in all cases, the diagnosis of the disease should be confirmed before chemotherapy; use fine-needle aspiration, cytology of fluid, or biopsy to confirm.

The best evidence of the advantages of neoadjuvant chemotherapy comes from a phase 3 trial (N Engl J Med. 2010;363:943-953).

Study participants with stage IIIC/IV ovarian, peritoneal, and fallopian tube carcinoma were randomized to receive either primary debulking surgery (followed by 6 cycles of platinum-based chemotherapy, which was mostly paclitaxel/carboplatin) or interval debulking surgery (which was preceded and followed by 3 cycles of the chemotherapy).

For the adjuvant and neoadjuvant groups, median overall survival was similar (29 vs 30 months), said Dr. Johnston. However, there were fewer complications in the neoadjuvant group, she said.

Those complications, as reported by Medscape Medical News when the study was first presented, included a statistically significant reduction in postoperative deaths in the adjuvant and neoadjuvant cohorts (6.0% vs 2.7%). The other reductions included grade 3/4 postoperative fever (8.0% vs 2.0%), grade 3/4 hemorrhage (7.0% vs 1.0%), and blood clots (2.4% vs 0.3%).

National Comprehensive Cancer Network (NCCN) 17th Annual Conference. Presented March 15, 2012.