Causes of treatment failure in gestational trophoblastic disease

Fifty-three (9.8%) of 539 patients with gestational trophoblastic tumors (invasive mole or choriocarcinoma) referred to the John I. Brewer Trophoblastic Disease Center, Northwestern University Medical School, from 1962 to 1986 died. They all had histologically documented choriocarcinoma. The time from the pregnancy event to treatment and the pretreatment human chorionic gonadotropin level were both significantly greater in the 53 patients who died as compared to the 486 who were cured. Seventy percent of fatal cases developed in association with term or preterm pregnancies, abortions or ectopic pregnancies rather than hydatidiform moles. Fifty-one percent of patients who died had brain, liver and/or peritoneal metastases at diagnosis. Ninety-six percent of patients had a Bagshawe score of ≥8 (high-risk group): the average score was 13. The most common causes of death were hemorrhage from one or more metastatic sites (42%) and pulmonary insufficiency (31%). Factors primarily responsible for the treatment failures in these patients were: (1) presence of extensive choriocarcinoma at the time of diagnosis, (2) lack of appropriately aggressive initial treatment in high-risk patients, and (3) failure of presently used treatment protocols to control advanced disease. Secondary chemotherapy and radiotherapy to sites other than the brain failed to improve survival. Adjuvant surgical procedures, especially hysterectomy and thoracotomy, may be useful for excising localized, chemotherapy-resistant tumors.