Which tumor types produce human chorionic gonadotropin (hCG)?
For more than 30 years, laboratories have used serum hCG testing in patients with gynecological and germ cell tumors to aid in evaluating therapeutic response and recurrence or metastasis. The use of hCG as a tumor marker is most common in seminomatous and nonseminomatous testicular tumors, ovarian germ cell tumors, the gestational trophoblastic diseases (GTDs) hydatidiform mole and choriocarcinoma, and nontesticular teratomas. Other tumor types that are more rarely associated with hCG elevations include hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers.
Can laboratories use hCG pregnancy assays for tumor marker testing?
Interestingly, there are currently no Food and Drug Administration-approved hCG assays specifically intended for use in cancer patients. This means that the only hCG tests available are pregnancy assays and that their use for tumor monitoring is considered off-label. However, published reviews have shown that several of these assays have sufficiently broad specificity and sensitivity to justify their use in oncology settings. These include assays such as the Immulite 2000, Elecsys 2010, Advia Centaur Total hCG, and the Architect Total hCG.
Like most serum hCG immunoassays, the tests above are designed to pick up as many hCG isoforms as possible. They recognize the holo-hormone (an alpha-subunit bound to a beta-subunit), “nicked” or unglycosylated forms of hCG, as well as hyperglycosylated forms, beta-core fragments, and free beta-subunits. There are also assays that specifically measure free alpha- and beta-subunits. This is noteworthy because, in malignant cells, the balanced ratio of alpha- and beta-subunits can be altered, leading to the secretion of excess free alpha- and beta-subunits. Some laboratories offer these independent alpha and beta measurements, but they are less commonly used than total hCG assays.
When is hCG monitoring specifically recommended?
According to clinical practice guidelines from numerous medical associations, the use of hCG as a tumor marker is limited to a few specific settings. These guidelines recommend it in the workup and monitoring of patients with suspected or known germ cell tumors of the testes and patients with GTD.
However, there is less consensus about using hCG in patients with germ cell tumors of the ovary, as ovarian cancer monitoring is more commonly performed using the tumor marker CA-125. The European Group on Tumor Markers as well as AACC Academy do not recommend routine use of hCG for ovarian tumors, while the National Comprehensive Cancer Network states that hCG can be measured to assess less common ovarian histopathologies.
How frequently should hCG be measured in cancer patients?
AACC Academy has made recommendations concerning the frequency of tumor marker measurements in the follow-up of testicular cancer. They recommend four to six tests per year for the first 2 years post-treatment and two tests per year thereafter. They specifically note that up to 12 tests may be useful during the first year in germ cell tumors of advanced stage. Importantly, since individuals serve as their own baseline, increases in hCG within a specific patient are more important than the absolute concentration and a single increasing value should be confirmed with repeat testing.
In GTD, hCG monitoring is typically performed over a shorter period of time with a higher frequency in an effort to monitor short-term chemotherapy (such as methotrexate). Post-molar gestational trophoblastic neoplasia is indicated if hCG values plateau over a period of at least 3 weeks or increase over a 2 week period. AACC Academy also recommends that hCG values be checked 6 months after evacuation to confirm treatment. Other associations recommend that hCG testing in GTD be done every 14 days, following 14-day methotrexate or dactinomycin treatment, until hCG levels return to normal.