NCCN Issues Guidelines for Management of Rare Gestational Cancers

Jason Harris
Published: Thursday, Oct 18, 2018
Nadeem R. Abu-Rustum, MD

Nadeem R. Abu-Rustum, MD

The National Comprehensive Cancer Network (NCCN) has issued the first-ever guidelines for the treatment of women with gestational trophoblastic neoplasia (GTN), a rare set of tumors that develop from placental cells. The guidelines recommend single-agent chemotherapy for most patients with low-risk disease; surgery and combination chemotherapy are advised for patients with high-risk GTN.1

The rarity of these cancers makes it unlikely that most oncologists and other clinicians will develop enough hands-on experience with them to become expert in their management, which is why a team of NCCN panelists from nearly 30 institutes worked more than a year to develop these guidelines. The American Cancer Society (ACS) estimates that GTN develops in roughly 1 of 1000 pregnancies in the United States.2 GTN is more prevalent in Asian and African countries.

Sometimes known as gestational trophoblastic disease, GTN occurs during pregnancy. Nadeem R. Abu-Rustum, MD, chief of the Gynecology Service at Memorial Sloan Kettering Cancer Center in New York, New York, and vice chair of the NCCN GTN panel, said in an interview that even experienced gynecologic oncologists struggle to manage GTN. “Gestational trophoblastic neoplasia is a rare disease and a complex disease,” he said. “It’s not common, and you require centralization and high volumes to become an expert.”

“We felt it was important to develop guidelines for the treatment of these diseases [because] most practicing oncologists, whether they’re medical oncologists or gynecologic oncologists who will be seeing and treating these patients, have never seen one of these patients before,” added John R. Lurain, MD, the Marcia Stenn professor of Gynecologic Oncology at Northwestern University Feinberg School of Medicine in Chicago and a member of the guideline-writing committee. “Although there’s a pretty robust literature, we thought it was important to present this information in a concise form.”

Most GTN appears in the form of partial or complete noninvasive hydatidiform moles, a mass that can form inside the womb during early pregnancy, resulting in an abnormal fetus. Surgery, usually suction dilation and curettage, is often the only treatment necessary if the disease has not spread beyond the uterus. Hysterectomy is also an option for women who aren’t planning to have children in the future.

These women should be monitored by human chorionic gonadotropin (hCG) assay every 1 to 2 weeks until hCG levels are normal for 3 consecutive assays. The hCG levels should then be tested twice in 3-month intervals. If hCG continues to rise or the patient has extrauterine disease, she should proceed to the same chemotherapy regimen as women with low-risk (FIGO prognostic score <7) GTN (Table).

These women are assigned to single-agent methotrexate or dactinomycin, or methotrexate/ leucovorin. The guidelines recommend a regimen of multiday methotrexate as frontline therapy. Because of its toxicity profile, dactinomycin is generally used in the second line for patients with methotrexate toxicity or effusions that contraindicate the use of methotrexate. NCCN recommends against using a dactinomycin pulse regimen as secondary therapy for patients with methotrexate- resistant disease or as primary therapy for choriocarcinoma.

These patients should undergo hCG assessment at the start of each treatment cycle. Those who have a good response to initial therapy and normal hCG levels can continue systemic therapy for 2 cycles, or 4 weeks, beyond hCG normalization, followed by an annual hCG assessment. The NCCN also recommends oral contraception for those patients.

The guidelines call for close hCG monitoring at all stages of disease and treatment. Abu-Rustum said the same test used to check for pregnancy also serves as the main blood test used to quantitatively monitor disease and indicate resolution.

“[Human chorionic gonadotropin] is like the perfect tumor marker, which we don’t have with other disease,” Lurain said in an interview with OncologyLive®. “We can use that to decide which patients need treatment based on the fall to normal [hCG levels] or persistent disease.

Figure. NCCN Guidelines for Treatment of Gestational Trophoblastic Neoplasia

Figure. NCCN Guidelines for Treatment of Gestational Trophoblastic Neoplasia
He added that these guidelines are also meant to be educational. Because GTN is rare, few oncologists, even gynecologic oncologists, are familiar with the disease. According to the ACS, almost all women with complete or partial moles and low-risk GTN can be cured, and cure rates are high for placental-site trophoblastic tumors. The prognosis is not as good if the disease metastasizes beyond the uterus, but even for high-risk GTD, cure rates range from 80% to 90%.

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