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Licensed Unlicensed Requires Authentication Published by De Gruyter June 13, 2019

A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer

  • Simona Ferraro EMAIL logo and Mauro Panteghini

Abstract

Clinical practice guidelines for the management of germ cell tumors recommend the measurements of human chorionic gonadotropin (hCG) and/or free hCGβ subunit for earlier diagnosis/recognition of the residual disease, for the prognostic evaluation and for the post-chemotherapy surveillance. However, the marketed hCG assays are validated and approved only for pregnancy purposes, with the sole exception of the Elecsys ‘hCG+β’ assay (Roche Diagnostics), cleared in Europe for oncological application. Theoretically, the hCG assay design for oncological purposes should fulfil the recommendations of the International Society of Oncology and Biomarkers requiring the use of antibodies displaying an equimolar recognition of both intact hCG and hCGβ monomer. Further analytical requirements should also be considered, such as optimal analytical sensitivity to allow an early tumor detection and low cross-reactivity for luteinizing hormone (LH). For the Elecsys assay, the detection limit (0.2 U/L) and the reported cross-reactivity for LH (0.12%) may be considered adequate if compared with the recommended requirements. Another issue is the definition of decision limits for oncologic purposes. After 3 years of clinical experience using the Elecsys assay in the oncology setting, we were able to define limits partitioned by sex and age as follows: males <50 years, 0.3 U/L; males >50 years, 2.3 U/L; female <50 years, 2.1 U/L; female >50 years, 5.6 U/L. There is an urgent need to disseminate appropriate educational information and to boost the clinical use of selective, highly sensitive and precise assays, specifically manufactured for cancer application.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Horwich A, Shipley J, Huddart R. Testicular germ-cell cancer. Lancet 2006;367:754–65.10.1016/S0140-6736(06)68305-0Search in Google Scholar

2. Gilligan TD, Seidenfeld J, Basch EM, Einhorn LH, Fancher T, Smith DC, et al. American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol 2010;28:3388–404.10.1200/JCO.2009.26.4481Search in Google Scholar

3. Ferraro S, Trevisiol C, Gion M, Panteghini M. Human chorionic gonadotropin assays for testicular tumors: closing the gap between clinical and laboratory practice. Clin Chem 2018;64:270–8.10.1373/clinchem.2017.275263Search in Google Scholar

4. Berger P, Paus E, Hemken PM, Sturgeon C, Stewart WW, Skinner JP, et al. Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop. Tumour Biol 2013;34:4033–57.10.1007/s13277-013-0994-6Search in Google Scholar

5. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 2008;54:e11–79.10.1373/clinchem.2008.105601Search in Google Scholar

6. Anckaert E, Ver Elst K, Mees M, Lecomte S, De Bock S, Schiettecatte J. Analytical and clinical evaluation of a human chorionic gonadotrophin plus β (hCG+βhCG) immunoassay in germ cell tumours and gestational trophoblastic disease. Immuno-Anal Biol Spe 2005;20:11–5.10.1016/j.immbio.2004.12.003Search in Google Scholar

7. Lempiäinen A, Hotakainen K, Blomqvist C, Alfthan H, Stenman UH. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma. Clin Chem 2007;53:1560–1.10.1373/clinchem.2007.088518Search in Google Scholar

8. Sölétormos G, Schiøler V, Nielsen D, Skovsgaard T, Dombernowsky P. Interpretation of results for tumor markers on the basis of analytical imprecision and biological variation. Clin Chem 1993;39:2077–83.10.1093/clinchem/39.10.2077Search in Google Scholar

9. Lange PH, Vogelzang NJ, Goldman A, Kennedy BJ, Fraley EE. Marker half-life analysis as a prognostic tool in testicular cancer. J Urol 1982;128:708–11.10.1016/S0022-5347(17)53149-3Search in Google Scholar

10. Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol 2014;15:1442–50.10.1016/S1470-2045(14)70490-5Search in Google Scholar

11. Wymer KM, Pearce SM, Harris KT, Pierorazio PM, Daneshmand S, Eggener SE. Adherence to National Comprehensive Cancer Network® Guidelines for Testicular Cancer. J Urol 2017;197:684–9.10.1016/j.juro.2016.09.073Search in Google Scholar PubMed

12. Cathomas R, Klingbiel D, Bernard BD, Lorch A, del Muro XG, Morelli F, et al. FDG PET scan (PET) positive residual lesions after chemotherapy (chemo) for metastatic seminoma: results of an International Global Germ Cell Cancer Group (G3) registry. J Clin Oncol 2017;35(Suppl):abstract 4521.10.1200/JCO.2017.35.15_suppl.4521Search in Google Scholar

13. Fizazi K, Culine S, Kramar A, Amato RJ, Bouzy J, Chen I, et al. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. J Clin Oncol 2004;22:3868–76.10.1200/JCO.2004.04.008Search in Google Scholar PubMed

14. Alfthan H, Haglund C, Dabek J, Stenman UH. Concentrations of human choriogonadotropin, its beta-subunit, and the core fragment of the beta-subunit in serum and urine of men and nonpregnant women. Clin Chem 1992;38:1981–7.10.1093/clinchem/38.10.1981Search in Google Scholar

15. Cole LA, Gutierrez JM. Production of human chorionic gonadotropin during the normal menstrual cycle. J Reprod Med 2009;54:245–50.Search in Google Scholar

Received: 2019-03-21
Accepted: 2019-05-01
Published Online: 2019-06-13
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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