Recurrent ovarian cancer

HOLLYWOOD, FLA. -- Major changes to national guidelines for ovarian cancer staging and treatment include recommendations for women with borderline or low-malignancy disease, updated chemotherapy recommendations, and additional options for recurrent disease that incorporate new agents.

"This is an era of hope," Dr. Robert J. Morgan Jr. said at the annual conference of the National Comprehensive Cancer Network. "We're seeing median survivals now of up to 5 years, and we're going to continue to see slow improvements in survival over time."

Epithelial ovarian cancer remains the leading cause of death from gynecologic cancer in the United States. Last year, there were an estimated 23,400 new diagnoses and about 13,900 deaths from this disease, according to the NCCN guidelines, which are compiled by a panel of 18 physician experts from leading cancer treatment centers nationwide.

Feedback since the last update in 1998 indicated a need for guidance on patients with borderline tumors, noted Dr. Morgan, staff physician in the department of medical oncology and therapeutics research at City of Hope Cancer Center, Duarte, Calif.

The definition of epithelial ovarian cancer of low malignant potential is a tumor with histologic features suggesting malignancy, but clinical behavior that suggests an excellent prognosis (more than 80% survival at 5 years). The term "low malignant potential" is preferred because "it is confusing to physicians as well as patients when you use the term 'borderline tumor,'" said Dr. Benjamin Greer, director of gynecologic oncology at the University of Washington in Seattle.

Clinicians may be unsure which patients to treat and which ones to merely observe because the potential lethal harm to these patients is small, Dr. Greer said. "Good pathology is critical to make the right decision for the patient."

The pathologic definition of low-malignant-potential disease is the gross appearance of peritoneal carcinomatosis and a microscopic appearance that characteristically fails to reveal evidence of frank invasion by the tumor nodules."

Women with ovarian cancer of low malignant potential tend to be younger, and are often diagnosed with stage I disease. The guidelines panel suggested asking patients about their fertility wishes preoperatively, and possibly delaying hysterectomy until after childbearing. A unilateral oophorectomy may be performed at the time of comprehensive staging if the woman desires to maintain her fertility; otherwise standard debulking surgery is recommended, accompanied by comprehensive staging.

Treatment after comprehensive staging is dictated by the presence or absence of invasive implants. There was no consensus among the experts regarding a preferred initial therapy. Those with invasive implants can either be observed or treated according to epithelial ovarian cancer guide-lines. For those women with noninvasive implants, the panel recommended monitoring and observation every 2-4 months for 2 years and every 6 months for 3 years.

The same follow-up schedule is recommended for women with a complete response to treatment for any stage of the disease.

In addition, a complete blood count is recommended every 12 months; CA 125 assessment at each visit if initially elevated; a chemistry profile; physical evaluation including a pelvic exam; and an abdominal-pelvic CT scan and chest x-ray as clinically indicated.

The guidelines feature new, alternative chemotherapy regimens. The preferred regimen for stage IA or IB (grade 2 or 3 tumors), stage IC, and stage II patients remained the same: carboplatin, AUC 5.0-7.5 plus paclitaxel, 175 mg/[m.sup.2], over 3 hours for three to six cycles, and the same regimen for stage III or IV disease for six cycles. Other options are a regimen of cisplatin, 75 mg/[m.sup.2] plus paclitaxel, 135 mg/[m.sup.2] over 24 hours or docetaxel/carboplatin, AUC 5-6.

Abdominal-pelvic radiotherapy is suggested as an adjuvant to primary chemotherapy for patients with low bulk disease. The panel reportedly had a "major debate" over the role of this radiotherapy in these patients, and concluded "it's OK as long as an institution has expertise," Dr. Morgan said, "but most institutions still consider chemotherapy first-line treatment in advanced disease."

The guidelines suggest a number of therapeutic options for ancillary surgery and acceptable regimens in patients whose tumors progress on primary chemotherapy.

The authors of the guidelines note that patients whose tumors progress without clinical benefit on two consecutive, single-agent regimens are unlikely to benefit from additional chemotherapy, and may be offered the best supportive care or entry into a clinical trial.

The updated guidelines, which include algorithms for work-up, primary treatment (including surgery), primary chemotherapy, and secondary adjuvant therapy, can be found at www.nccn.org.