Gestation trophoblastic diseases: Management of cases with persistent low human chorionic gonadotropin results

As indicated by the USA hCG Reference Service experience, despite announcements by the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists regarding the importance of verifying the diagnosis of GTM before initiating therapy, there continues to be confusion among clinicians who manage these patients, and unfortunately patients are continuing to receive unnecessary therapy. It is known that at least one person died as a consequence of therapy for the misdiagnosis of choriocarcinoma and GTM. The goal is to improve public awareness about conditions that mimic GTM. These include false-positive hCG, quiescent gestational trophoblastic disease, and pituitary hCG. Some of these conditions are harmless, but in the case of quiescent hCG, there is a very real possibility for malignant transformation. In this special circumstance, close follow-up is critical, but therapy should be withheld until there are sharply increasing hCG results, most notably those over 100 mIU/mL [34,35]. This is particularly relevant for the patient with a recent or remote history of hydatidiform mole or GTM. Under these circumstances, the first step is to confirm the diagnosis using a different laboratory and hCG test. If results are very different (more than twofold) then false-positive hCG is likely. If the patient is over 45 years old or postoophorectomy, then pituitary hCG should be considered as the likely cause, regardless of history, and can be confirmed with 2 weeks or so of combination estrogen-progesterone therapy, which suppresses the hCG result in patients with this diagnosis. This is in keeping with currently recommended guidelines in patients undergoing postmolar surveillance, that all such patients undergo oral contraception for up to a year following evacuation of a molar pregnancy. This practice also excludes the complications of pituitary hCG. In patients following the diagnosis of hydatidiform mole, GTM, or choriocarcinoma, if there is complete resolution of measurable hCG, and then titers slowly rise and then plateau, this is indicative of quiescent gestational trophoblastic disease. This condition is not likely to respond to chemotherapy [1-7]. It is important to discriminate whether newly rising hCG is leading to a plateau (quiescent disease) or will continuously rise (malignant disease). In some cases, following treatment of a molar pregnancy or GTM, the hCG plateaus below 250 mIU/mL. This can also be consistent with the diagnosis of quiescent gestational trophoblastic disease, and does not respond to therapy [1-7]. The diagnosis of quiescent disease can be readily confirmed by showing the absence of Hg-hCG (<0.3 ng/mL). This test is approved by the Food and Drug Administration and readily available at national clinical laboratories (Nichols Institute Laboratories, Invasive Trophoblast Antigen test).