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Indication -
Cancer
Human chorionic gonadotrophin (hCG) (measured as total beta-hCG)
Assay formats
Immunoassay
Status history
First added in 2019
Changed in 2020
Purpose type
Aid to diagnosis, Monitoring
Purpose
To aid in the diagnosis of and monitoring of germ cell tumours and gestational trophoblastic disease
Specimen types
Plasma
WHO prequalified or recommended products
N/A
WHO supporting documents
WHO classification of tumours of the urinary system and male genital organs. WHO classification of tumours, 4th edition, volume 8. https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Tumours-Of-The-Urinary-System-And-Male-Genital-Organs-2016;
WHO classification of tumours of female reproductive organs. WHO classification of tumours, 4th edition, volume 6. https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classific ation-Of-Tumours-Of-Female-Reproductive-Organs-2014
Codes
ICD11 code:
2D4Y
Summary of evidence evaluation
Although guideline recommendations for using the sum of hCG and β-hCG for the diagnosis and surveillance of germ-cell tumours and gestational trophoblastic disease are clear, the evidence upon which they are based was not evident in the submission. Evidence from trials was provided that showed that tailoring chemotherapy for the treatment of germ-cell tumours with an unfavourable decrease in tumour markers (based in part on hCG assessment) was beneficial and prognostic (8).
Summary of SAGE IVD deliberations
Use of hCG for monitoring germ-cell tumours, which are generally diagnosed in young patients, permits classification of risk for advanced disease while it is still amenable to curative treatment and to adapt the treatment according to the level of hCG detected. The availability of hCG testing allows accurate treatment and prognosis of cancers, prescription of treatments listed in the WHO EML and avoidance of over-treatment. Moreover, the kinetics of hCG is associated with better prediction of resistance to treatment, as a basis for a timely change of the cytotoxic regimen.
SAGE IVD recommendation
The SAGE IVD recommended conditional inclusion on the EDL of the test for the sum of hCG and β-hCG for the diagnosis and surveillance of germ-cell tumours
and gestational trophoblastic disease, pending submission of more evidence of reference ranges for the general population of men and women in the countries and ethnic population in which the test will be used. The group proposed that proficiency testing or an external quality assurance programme be introduced to ensure local performance of the assay.
Details of submission from 2020
Background
Disease condition and impact on patients: Germ-cell malignancies (testicular, ovarian, non-genital midline and unknown primary germ-cell tumours) and trophoblastic disease are highly curable. They arise more commonly in younger patients, including during pregnancy (gestational trophoblastic disease), which is associated with high potential economic loss for countries. The use of hCG for monitoring and prognosis of germ-cell tumours and gestational trophoblastic disease is recommended by established, recognized professional society guidelines (1, 2). Some non-gestational malignancies express genes for the β subunit of hCG, resulting in activation and production of low levels of hyperglycosylated free β subunit, which may become a useful marker or prognostic factor for these tumours (3). Gestational trophoblastic neoplasia may have cytotrophoblasts that produce hyperhydroxylated hCG.
Does this test meet a medical need? Use of hCG for monitoring and prognosis is recommended by the guidelines of established professional societies for germ- cell tumours (testicular, ovarian, non-genital midline and unknow primary) and gestational trophoblastic disease (4–6). hCG has been used to determine the prognosis of germ-cell tumours to classify risk in advanced tumours (7) and in
monitoring the response of non-seminomatous germ-cell tumours to anticipate resistance to platinum-based regimens and to intensify treatment (8, 9).
How this test is used: For monitoring and prognosis of germ-cell tumours and diagnosis, prognosis and monitoring of gestational trophoblastic disease.
Public health relevance
Prevalence: Testicular cancer is diagnosed in approximately 9600 men each year in the USA, but only approximately 400 men die of their disease (4.2%). According to IARC (1), in 2018 in LMICs, 11 290 new cases of testicular cancer were reported, with 3984 deaths (35.3%). Testicular cancer is the diagnosed mainly young males. The global prevalence is 284 073 cases.
Socioeconomic impact: Germ-cell tumours arise mainly in young people; timely access to treatment, surgery, chemotherapy and radiotherapy can substantially increase survival when delivered with curative intention at all the stages of disease. According to IARC (1), testicular cancer is diagnosed mainly in men aged 20–34 years. Disparities in survival from testicular cancer have been described, with a large gap between high-income countries (mortality to incidence ratio: 0.03) and LMICs (0.17).
WHO or other clinical guidelines relevant to the test
WHO guidelines list β-hCG for prognosis and response to treatment (3, 4).
Evidence for clinical usefulness and impact
No relevant comparative studies of cost or cost–effectiveness were identified. Assessment of hCG in blood samples does not require highly specialized laboratory personnel and is considered a standard laboratory biochemical analysis.
of non-seminomatous germ-cell tumours to anticipate platinum resistance and intensify the treatment in a personalized approach (8, 9).
Evidence for economic impact and/or cost–effectiveness
Consent is required to obtain a plasma sample. Use of hCG for monitoring germ-cell tumours, which are generally diagnosed in young patients, permits classification of risk for advanced disease that is still amenable to curative treatment in a high percentage of cases and adaptation of treatment according to risk. The availability of hCG testing allows accurate cancer treatment and prognostication of cancers and can also avoid over-treatment. hCG is also associated with better prediction of resistance to treatment, allowing a timely change of cytotoxic regimen.
Ethical issues, equity and human rights issues
Consent is required to obtain a plasma sample. Use of hCG for monitoring germ-cell tumours, which are generally diagnosed in young patients, permits classification of risk for advanced disease that is still amenable to curative treatment in a high percentage of cases and adaptation of treatment according to risk. The availability of hCG testing allows accurate cancer treatment and prognostication of cancers and can also avoid over-treatment. hCG is also associated with better prediction of resistance to treatment, allowing a timely change of cytotoxic regimen.
1. Tavassoli FA, Devilee P, editors. Pathology and genetics of tumours of the breast and female genital organs (WHO classification of tumours, 3rd Edition), Vol. 4, Chapter 2. Germ cell tumours. Lyon: International Agency for Research on Cancer; 2003.
2. Honecker F, Aparicio J, Berney D, Beyer J, Bokemeyer C, Cathomas R, et al. ESMO 2018 Consensus Conference guidelines on testicular germ-cell cancer: diagnosis, treatment and follow-up. Ann Oncol. 2018;29:1658–86.
3. Acevedo HF, Tong JY, Hartsock RJ. Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins. Cancer 1995;76:1467.
4. Testicular cancer, version 2018. Fort Washington (PA): National Comprehensive Cancer Network; 2018.
5. Clinical guidelines for the management of testicular cancer. Arnhem: European Association of Urology; 2018 (https://uroweb.org/guideline/testicular-cancer/, accessed August 2019).
6. Seckl MJ, Sebire NJ, Fisher RA, Golfier F, Massuger L, Sessa C. Gestational trophoblastic disease. ESMO clinical practice guidelines. Ann Oncol. 2013;24(Suppl 6):vi39–50.
7. International Germ Cell Collaborative Group. International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ-cell tumours. J Clin Oncol. 1997;15(2):594–603.
8. Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L. et al. hCG has a relevant role in monitoring for treatment effectiveness and tailoring chemotherapy according to tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014;15(13):1442–50.
9. Fizazi K, Flechon A, Le Teuff G, Mardiak J, Pagliaro LC, Geoffrois L, et al. Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT). J Clin Oncol. 2016;34 (Suppl):abstract 4504.
10. Ferraro S, Trevisol C, Gion M, Panteghini, M. Review: Human Chorionic Gonadotropin Assays for Testicular Tumors: Closing the Gap between Clinical and Laboratory Practice. J. Clin. Chem. 2018; 64(2): 270-278.