Choriocarcinoma

What choriocarcinoma is

During pregnancy, trophoblast cells invade the wall of the uterus and build the placenta. They make human chorionic gonadotropin (hCG), the hormone detected by pregnancy tests. In choriocarcinoma, these cells become malignant. They invade blood vessels, bleed easily and keep producing hCG.

Choriocarcinoma belongs to a family called gestational trophoblastic disease, which ranges from benign molar pregnancy to cancers grouped as gestational trophoblastic neoplasia (GTN). Because the tumor makes hCG, blood hCG levels act as a precise tumor marker for diagnosis, treatment response and follow-up.

Gestational vs non-gestational choriocarcinoma

The rest of this page focuses on gestational choriocarcinoma, the more common form. In men, choriocarcinoma appears as part of testicular cancer and is treated as a germ cell tumor.

Causes and risk factors

Choriocarcinoma can follow any pregnancy:

• About half follow a molar pregnancy, especially a complete mole.
• About a quarter follow a miscarriage, abortion or ectopic pregnancy.
• About a quarter follow a normal pregnancy, sometimes months or years later.

Risk is higher with a previous molar pregnancy, in women over 40 or under about 20 at conception, and in some parts of Asia and Africa where molar pregnancy is more common.

Symptoms

Symptoms depend on where the tumor is growing:

• Uterus: irregular or persistent vaginal bleeding after a pregnancy, an enlarged uterus and pelvic pain.
• Lungs (the commonest site of spread): cough, coughing up blood, chest pain and breathlessness.
• Vagina: dark purple, bleeding nodules.
• Brain: headache, vomiting, seizures, weakness or vision changes.
• Liver: pain under the right ribs and internal bleeding.
• Hormonal effects: very high hCG can cause nausea, breast tenderness and an overactive thyroid, because hCG weakly stimulates the thyroid gland.

Some women have no uterine bleeding at all and are first diagnosed after a chest X-ray or brain scan shows unexplained spots. Any woman of reproductive age with unexplained bleeding in the lungs, brain or liver should have an hCG test.

Diagnosis

1. Serum hCG: a blood test that measures the exact level. A high level with no ongoing pregnancy strongly suggests trophoblastic disease. Serial tests show whether it is rising or plateauing.
2. Pelvic ultrasound: to rule out a new pregnancy and look for a mass in the uterus.
3. Staging scans: chest X-ray or CT, CT of the abdomen and MRI of the brain to find spread.
4. Tissue diagnosis: when available from a uterine sample, it confirms the diagnosis. Biopsy of metastases is often avoided because these tumors bleed heavily.

Doctors then assign a FIGO stage (I to IV) and a WHO prognostic score based on factors such as age, hCG level, the type of preceding pregnancy, time since it ended, tumor size, the number and sites of metastases and previous treatment. A score of 0 to 6 is low risk. A score of 7 or more is high risk.

Treatment

Treatment is usually given at a specialist trophoblastic disease center.

• Low-risk disease: single-drug chemotherapy, usually methotrexate or actinomycin D, repeated until hCG is normal and then for a few extra cycles.
• High-risk disease: combination chemotherapy such as EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine).
• Brain or liver spread: may need adjusted chemotherapy, radiotherapy or surgery.
• Surgery: hysterectomy is sometimes used for drug-resistant disease in the uterus or to control bleeding, but most women keep their uterus.
• Resistant disease: second-line chemotherapy and immunotherapy (checkpoint inhibitors) are options.

Follow-up, fertility and outlook

After treatment, hCG is checked regularly, often for about a year, because a rise is the earliest sign of relapse. Doctors advise avoiding pregnancy until monitoring is complete so that a new pregnancy does not hide a relapse. Reliable contraception is important during this time.

Most women keep their fertility and go on to have healthy pregnancies. The risk of another molar pregnancy is slightly raised, so an early ultrasound and an hCG check after each future pregnancy are recommended. Cure rates are close to 100% for low-risk disease and around 80% to 90% or higher for high-risk disease treated at specialist centers. Non-gestational choriocarcinoma has a less favorable outlook.

Frequently asked questions

What are the first symptoms of choriocarcinoma?

The commonest first sign is irregular vaginal bleeding weeks or months after a pregnancy, including a molar pregnancy or miscarriage. A pregnancy test may stay positive. Some women first notice a cough, coughing up blood, or headaches if the cancer has spread to the lungs or brain.

What hCG level suggests choriocarcinoma?

There is no single cut-off. Doctors look at the trend. An hCG level that rises or stays flat over several weeks after a pregnancy has ended, with no new pregnancy, suggests trophoblastic neoplasia. Levels can be very high, sometimes above 100,000 IU/L, which adds to the risk score.

Is choriocarcinoma curable?

Yes. Gestational choriocarcinoma is among the most curable cancers, even when it has spread. Low-risk disease is cured in almost all cases with single-drug chemotherapy, and most high-risk patients are cured with combination chemotherapy at specialist centers.

Can you get pregnant after choriocarcinoma?

Usually yes. Most women keep their uterus and fertility. Doctors recommend waiting until hCG follow-up is complete, often about a year after chemotherapy ends, and having an early ultrasound and hCG check in any later pregnancy.

Can men get choriocarcinoma?

Yes, but in men it arises in the testis as a germ cell tumor, often mixed with other tumor types. It tends to spread early and is treated with surgery to remove the testis plus combination chemotherapy. Its outlook is less favorable than the gestational form.