Gestational Trophoblastic Disease: Plain-Language Guide

This page is for anyone facing gestational trophoblastic disease (GTD), a rare group of growths that start from pregnancy tissue. It walks through what the National Cancer Institute's PDQ summary says about risk, symptoms, staging, treatment, and the blood test used to track it.

Gestational trophoblastic disease, usually shortened to GTD, is a broad term. NCI's PDQ summary for health professionals defines it as covering both benign (not cancer) and malignant (cancer) growths. These arise from products of conception in the uterus, meaning tissue that forms after an egg is fertilized.

One biological fact explains much of what follows. GTDs contain chromosomes from the father and come from the placenta, not from the mother's own tissue. The tissue that grows abnormally is the tissue that would have formed the placenta.

PDQ reports incidence figures that vary enormously by country, and says part of that variation comes from differences in diagnostic criteria and reporting.

The reported range runs from 23 per 100,000 pregnancies in Paraguay to 1,299 per 100,000 in Indonesia. In the United States, the reported incidence is about 110 to 120 per 100,000 pregnancies.

Choriocarcinoma, which PDQ calls the most aggressive form, is rarer. The US reported incidence is about 2 to 7 per 100,000 pregnancies. Expressed as an age-standardized rate, that is about 0.18 per 100,000 women aged 15 to 49.

PDQ says two factors have consistently been associated with increased GTD risk: maternal age and a history of hydatidiform mole, often written HM. A hydatidiform mole, also called a molar pregnancy, is an abnormal growth of placenta tissue in place of a normal pregnancy.

The mole history figure is specific. After one previous hydatidiform mole, PDQ puts the risk of a mole in a later pregnancy at 1%. After more than one prior mole, that rises to approximately 25%.

Age risk is bimodal, meaning it rises at both ends. PDQ describes increased risk for mothers younger than 20 and older than 35. Relative risks run from 1.1 to 11 compared with ages 20 to 35.

A registry study PDQ cites complicates that picture usefully. Complete moles were highest in women under 20, then fell steadily with age. Partial moles rose across the whole age range. PDQ says that suggests different causes for the two.

The negatives are worth stating too. PDQ says the link with paternal age is inconsistent. It adds that many exposures have been examined with no clear links found. Those include tobacco smoking, alcohol, diet, and oral contraceptive use.

PDQ names the two most common first symptoms: vaginal bleeding, and a rapidly enlarging uterus. It says GTD should be considered whenever a woman who has not reached menopause has those findings.

Most GTD types raise human chorionic gonadotropin, or hCG, the hormone a pregnancy test detects. So PDQ says an hCG blood level and a pelvic ultrasound are the first steps in the workup.

Other signs PDQ lists are worth recognizing, because several look like ordinary pregnancy complications.

• Pelvic pain, or a sense of pressure.
• Anemia, meaning a low red blood cell count.
• Hyperemesis gravidarum, which is severe vomiting in pregnancy.
• Hyperthyroidism, meaning an overactive thyroid gland.
• Preeclampsia (dangerously high blood pressure in pregnancy) early in pregnancy.

The thyroid entry has a mechanism attached. PDQ explains that part of the hCG molecule looks so much like part of thyroid-stimulating hormone (TSH) that hCG can act a little like TSH.

PDQ says choriocarcinoma most often follows a molar pregnancy. But it can follow a normal pregnancy, an ectopic pregnancy (one that grows outside the uterus), or an abortion. PDQ says it should always be considered when bleeding continues after delivery.

PDQ states the prognosis for cure is good even when disease has reached distant organs. That holds especially when only the lungs are involved. Because of that, PDQ says the usual TNM staging system, which is based on tumor size, lymph nodes, and spread, does little to predict outcome here.

So GTD uses the FIGO system, from the Fédération Internationale de Gynécologie et d'Obstétrique, which PDQ says is the one most commonly used.

• Stage I. Tumors strictly confined to the uterine corpus (the main body of the uterus).
• Stage II. Tumors extending to the adnexa (the ovaries and fallopian tubes) or the vagina, but limited to genital structures.
• Stage III. Tumors extending to the lungs, with or without genital tract involvement.
• Stage IV. All other metastatic sites.

FIGO staging carries something unusual: a prognostic score appended to the stage. PDQ explains that the scores from eight risk factors are summed, then written after the Roman numeral separated by a colon, as in stage II:4 or stage IV:9.

The modified WHO scoring system uses eight factors:

• Age.
• The type of pregnancy that came before.
• The interval in months since that pregnancy.
• Pretreatment serum hCG (the blood level before treatment).
• Largest tumor size, counting the uterus.
• The sites of metastases (spread).
• The number of metastases.
• Any earlier chemotherapy that failed.

Some cut points are precise enough to look up on a report. Age scores 0 below 40, and 1 at 40 or over. The highest scores (4 points) go to an interval of more than 12 months, a pretreatment hCG above 100,000 IU/L, and more than 8 metastases. Ask your team to show you the full table.

PDQ adds a caution about all of it. A variety of risk scoring systems have been published, which makes comparing results across studies difficult.

Most hydatidiform moles are benign. PDQ says they are treated conservatively by dilation, suction evacuation, and curettage. In this procedure the cervix is gently opened, and the tissue is removed with suction and a small tool. Because they carry a risk of persisting or progressing, they must be followed carefully afterward.

For low-risk gestational trophoblastic neoplasia (GTD that has become a tumor needing treatment), defined as a FIGO score of 0 to 6, PDQ is candid. There is no consensus on the best first chemotherapy regimen. Regimens vary by geography and by institution. Most have not been compared head to head.

Then it gives the number that reframes everything. Initial remission rates may differ between regimens. But salvage, meaning switching to a different regimen when the first one does not work, is very effective. PDQ says ultimate cure rates are generally 99% or more.

A Cochrane systematic review PDQ cites found four randomized trials. The review compared pulsed dactinomycin with weekly methotrexate across 392 patients in total, and dactinomycin gave better complete response rates without salvage therapy. One arm was pulsed dactinomycin. The other was weekly methotrexate. Your treating team works out the amounts for you.

This is the most concrete part of GTD care, and the numbers are precise.

PDQ says the first regimen is generally continued until beta-hCG reaches a level the institution counts as normal. That level must hold for 3 consecutive weeks. Or treatment runs at least one cycle beyond the point where it normalized.

A salvage regimen is started if any of three things happens.

• The beta-hCG plateaus for 3 weeks, meaning it falls by 10% or less for 3 consecutive weeks.
• The beta-hCG rises by more than 20% for 2 consecutive weeks.
• Metastases appear.

These figures come from the National Cancer Institute’s “Gestational Trophoblastic Disease Treatment (PDQ).”

Those are checkable rules. Knowing them makes a weekly blood result readable rather than mysterious.

The organ involved is covered in uterine cancer. Diagnostic specifics are in GTD diagnosis questions, and drug specifics in GTD treatment questions.

• NCI PDQ: gestational trophoblastic disease, HP version