The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.
David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.
“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.
“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.
The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.
Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.
The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the.
The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.
The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.
For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.
The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.
For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).
“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.