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Gestational Trophoblastic Disease Treatment (PDQ®)

Health Professional Version
Last Modified: 04/12/2013

Treatment Option Overview

Low Levels of hCG
        False-positive hCG
        Pituitary hCG

Most hydatidiform moles (HMs) are benign and are treated conservatively by dilation, suction evacuation, and curettage. However, since they carry a risk of persistence or progression to malignant gestational trophoblastic disease (GTD), they must be followed carefully with weekly serum human chorionic gonadotropin (hCG) levels to normalization. Monthly follow-up for 6 months is generally recommended, although the duration of this phase of follow-up is not based on empiric study.

Prompt institution of therapy for GTD and continuing follow-up at very close intervals until normal beta-hCG titers are obtained is the cornerstone of management. When chemotherapy is instituted, the interval between courses should rarely exceed 14 to 21 days, depending on the regimen used. It is recommended that patients receive one to three courses of chemotherapy after the first normal beta-hCG titer, depending on the extent of disease. The modified World Health Organization (WHO) Prognostic Scoring System (see Table 1) should be utilized, and combination chemotherapy should be initiated when warranted by the patient's score. If a diagnosis of GTD is made, routine work-up includes the following:

  • Serum beta-hCG.
  • Blood work of liver, renal, and marrow function.
  • Chest x-ray.
  • Pelvic ultrasound.
  • Head computed tomography or magnetic resonance imaging (in the case of choriocarcinoma or central nervous system signs).

Treatment of GTD depends on the risk category determined by the Modified WHO Prognostic Scoring System as adapted by the International Federation of Gynecology and Obstetrics (see Table 1). Since the very rare placental-site trophoblastic tumors and the even more rare epithelioid trophoblastic tumors are biologically distinct entities, their management is discussed separately.

Low Levels of hCG

Accurate monitoring of hCG is critical to successfully diagnose and monitor the treatment course of gestational trophoblastic disease. False-positive results may lead to inappropriate diagnoses and treatment, and must be minimized. The following are possible alternate diagnoses to be considered in cases of low-level hCG.

False-positive hCG

Serum hCG testing relies on detecting two antibodies on the hCG molecule. The antibodies are polyclonal or monoclonal antibodies derived from various animals: mouse, rabbit, goat or sheep. Humans with heterophilic (or cross-species) antibodies bind the antibodies in the assay, leading to a false-positive result. This was a common problem with one of the commercially available assays until it was re-engineered in 2003. Heterophilic antibodies cannot cross the glomerular filtration barrier, so the performance of a urinary hCG can eliminate this source for a positive test result. The urine sample should be run using the same system generally reserved for serum, as opposed to over-the-counter urine-pregnancy tests, to avoid decreased sensitivity in the latter.

Pituitary hCG

The anterior stalk of the pituitary secretes luteinizing hormone (LH), which shares an alpha subunit with hCG. In normal menstrual cycles, pituitary generated hCG may be detectable at the time of the LH surge. Estrogen provides negative feedback for this LH secretion and acts as a suppressing agent. In patients in low-estrogen states (perimenopause, menopause, and status postoophorectomy), pituitary hCG may be secreted in increasing amounts, although only levels between 1 to 32 mIU/mL have been recorded.[1] To confirm a pituitary source for the hCG, patients are started on high-dose oral contraceptive pills to produce an exogenous source of estrogen. In general, patients with pituitary hCG will have their hCG levels suppressed after 3 weeks on this regimen.[1]

References
  1. Muller CY, Cole LA: The quagmire of hCG and hCG testing in gynecologic oncology. Gynecol Oncol 112 (3): 663-72, 2009.  [PUBMED Abstract]