Abstract
Serum tumor markers (STMs) play a critical role in the diagnosis, staging and follow-up of both seminomatous and nonseminomatous testicular germ cell neoplasms. Levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH), especially those measured after orchiectomy, also have implications for patient prognosis. Given that testicular germ cell tumors represent the most common solid tumor in men aged 20–34, radiologists must have familiarity with the clinical utilization and implications of these STMs. This article will review the classical patterns of STM elevation most commonly seen in pure seminomatous and nonseminomatous germ cell tumors while also providing case-based examples highlighting the importance of STM correlation with imaging. The role of STMs in clinical staging and disease surveillance will also be discussed.
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References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30. https://doi.org/10.3322/caac.21442.
Cancer Facts & Figures 2017 n.d.
Einhorn LH. Treatment of testicular cancer: a new and improved model. J Clin Oncol Off J Am Soc Clin Oncol 1990;8:1777–81. https://doi.org/10.1200/JCO.1990.8.11.1777.
Klein EA. Tumor markers in testis cancer. Urol Clin North Am 1993;20:67–73.
Williamson SR, Delahunt B, Magi-Galluzzi C, Algaba F, Egevad L, Ulbright TM, et al. The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 2017;70:335–46. https://doi.org/10.1111/his.13102.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers | Clinical Chemistry n.d.
Feldman DR. State-of-the-Art Management of Germ Cell Tumors. Am Soc Clin Oncol Educ Book 2018:319–23. https://doi.org/10.1200/edbk_201139.
Aparicio J, Maroto P, García del Muro X, Sánchez-Muñoz A, Gumà J, Margelí M, et al. Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG). Ann Oncol Off J Eur Soc Med Oncol 2014;25:2173–8. https://doi.org/10.1093/annonc/mdu437.
Motzer RJ, Jonasch E, Agarwal N, Beard C, Bhayani S, Bolger GB, et al. Testicular Cancer, Version 2.2016. J Natl Compr Cancer Netw JNCCN 2015;13:772–99.
Groll RJ, Warde P, Jewett M a. S. A comprehensive systematic review of testicular germ cell tumor surveillance. Crit Rev Oncol Hematol 2007;64:182–97. https://doi.org/10.1016/j.critrevonc.2007.04.014.
Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Borgonovo K, Lonati V, et al. Surveillance or Adjuvant Treatment With Chemotherapy or Radiotherapy in Stage I Seminoma: A Systematic Review and Meta-Analysis of 13 Studies. Clin Genitourin Cancer 2015;13:428–34. https://doi.org/10.1016/j.clgc.2015.04.005.
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 Off J Am Soc Clin Oncol 2010;28:3388–404. https://doi.org/10.1200/JCO.2009.26.4481.
Yuasa T, Yoshiki T, Ogawa O, Tanaka T, Isono T, Mishina M, et al. Detection of alpha-fetoprotein mRNA in seminoma. J Androl 1999;20:336–40.
Javadpour N. Significance of elevated serum alphafetoprotein (AFP) in seminoma. Cancer 1980;45:2166–8.
Morris MJ, Bosl GJ. Recognizing abnormal marker results that do not reflect disease in patients with germ cell tumors. J Urol 2000;163:796–801.
Stang A, Jansen L, Trabert B, Rusner C, Eberle A, Katalinic A, et al. Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002–2006: A high resolution study by histology and age. Cancer Epidemiol 2013;37:492–7. https://doi.org/10.1016/j.canep.2013.03.017.
Kaba M, Pirinççi N, Yüksel MB, Geçit İ, Güneş M, Demir M, et al. Serum Levels of Trace Elements in Patients with Testicular Cancers. Int Braz J Urol Off J Braz Soc Urol 2015;41:1101–7. https://doi.org/10.1590/S1677-5538.IBJU.2014.0460.
Logothetis CJ. The choriocarcinoma syndrome. Cancer Bull.1984;36:118 – 20. Original article that first describes the choriocar- cinoma syndrome. n.d.
Cole LA. Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol RBE 2010;8:102. https://doi.org/10.1186/1477-7827-8-102.
Reilley MJ, Pagliaro LC. Testicular choriocarcinoma: a rare variant that requires a unique treatment approach. Curr Oncol Rep 2015;17:2–2. https://doi.org/10.1007/s11912-014-0430-0.
Wei Y, Wu S, Lin T, He D, Li X, Liu J, et al. Testicular yolk sac tumors in children: a review of 61 patients over 19 years. World J Surg Oncol 2014;12. https://doi.org/10.1186/1477-7819-12-400.
Ross JH, Rybicki L, Kay R. Clinical behavior and a contemporary management algorithm for prepubertal testis tumors: a summary of the Prepubertal Testis Tumor Registry. J Urol 2002;168:1675–8; discussion 1678-1679. https://doi.org/10.1097/01.ju.0000030749.27823.f5.
Patel P, Balise R, Srinivas S. Variations in normal serum alpha-fetoprotein (AFP) levels in patients with testicular cancer on surveillance. Onkologie 2012;35:588–91. https://doi.org/10.1159/000342695.
Read G, Stenning SP, Cullen MH, Parkinson MC, Horwich A, Kaye SB, et al. Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol Off J Am Soc Clin Oncol 1992;10:1762–8. https://doi.org/10.1200/JCO.1992.10.11.1762.
Germà-Lluch JR, Garcia del Muro X, Maroto P, Paz-Ares L, Arranz JA, Gumà J, et al. Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG). Eur Urol 2002;42:553–62; discussion 562-563.
Beck SDW, Foster RS, Bihrle R, Donohue JP. Significance of primary tumor size and preorchiectomy serum tumor marker level in predicting pathologic stage at retroperitoneal lymph node dissection in clinical Stage A nonseminomatous germ cell tumors. Urology 2007;69:557–9. https://doi.org/10.1016/j.urology.2006.12.011.
Milose JC, Filson CP, Weizer AZ, Hafez KS, Montgomery JS. Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance. Open Access J Urol 2011;4:1–8. https://doi.org/10.2147/OAJU.S15063.
IInternational Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol Off J Am Soc Clin Oncol 1997;15:594–603. https://doi.org/10.1200/JCO.1997.15.2.594.
Atsü N, Eskiçorapçi S, Uner A, Ekici S, Güngen Y, Erkan I, et al. A novel surveillance protocol for stage I nonseminomatous germ cell testicular tumours. BJU Int 2003;92:32–5.
Nicolai N, Pizzocaro G. A surveillance study of clinical stage I nonseminomatous germ cell tumors of the testis: 10-year followup. J Urol 1995;154:1045–9.
Vugrin D, Cvitkovic E, Posner J, Hajdu S, Golbey RB. Neurological complications of malignant germ cell tumors of testis: biology of brain metastases (I). Cancer 1979;44:2349–53.
Kawanami K, Wakao N, Kamiya M, Takeuchi M, Hirasawa A, Takahashi E, et al. A case of mediastinal embryonal carcinoma successfully treated by integrative therapy. Nagoya J Med Sci 2014;76:225–33.
Pokharna P, Sharma N, Tiwari A, Devgaraha S, Mathur RM. Testicular embryonal cell carcinoma presenting as haemoptysis and skin nodules. Indian J Chest Dis Allied Sci 2014;56:125–7.
Moul JW, McCarthy WF, Fernandez EB, Sesterhenn IA. Percentage of embryonal carcinoma and of vascular invasion predicts pathological stage in clinical stage I nonseminomatous testicular cancer. Cancer Res 1994;54:362–4.
Gama R, Smith MG, White WF, Kwong P. Hyperthyroidism from an embryonal carcinoma. J R Soc Med 1997;90:446–7.
Richie J, Steele G. Neoplasms of the testis. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, editors. Campbell-Walsh Urology. Philadelphia, PA: Saunders; 2007. pp. 907–908 n.d.
Greene FL, Sobin LH. A worldwide approach to the TNM staging system: collaborative efforts of the AJCC and UICC. J Surg Oncol 2009;99:269–72. https://doi.org/10.1002/jso.21237.
NCCN Guidelines. NCCN Clin Pract Guidel Oncol Testic Cancer 22018 n.d. https://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf.
Oldenburg J, Fosså SD, Nuver J, Heidenreich A, Schmoll H-J, Bokemeyer C, et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24:vi125–32. https://doi.org/10.1093/annonc/mdt304.
Tandstad T, Cohn-Cedermark G, Dahl O, Stierner U, Cavallin-Stahl E, Bremnes RM, et al. Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study. Ann Oncol Off J Eur Soc Med Oncol 2010;21:1858–63. https://doi.org/10.1093/annonc/mdq026.
Gilligan TD, Hayes DF, Seidenfeld J, Temin S. ASCO Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors. J Oncol Pract 2010;6:199–202. https://doi.org/10.1200/JOP.777010.
Husband J, Barrett A, Peckham M. The role of computer tomography in the assessment of tumour volume in patients with malignant testicular teratoma. Br J Radiol 1981; 15:50-53.
Zon RT, Nichols C, Einhorn LH. Management strategies and outcomes of germ cell tumor patients with very high human chorionic gonadotropin levels. J Clin Oncol Off J Am Soc Clin Oncol 1998;16:1294–7. https://doi.org/10.1200/JCO.1998.16.4.1294.
Trigo JM, Tabernero JM, Paz-Ares L, García-Llano JL, Mora J, Lianes P, et al. Tumor markers at the time of recurrence in patients with germ cell tumors. Cancer 2000;88:162–8.
Husband JE, Koh D-M. Multimodality imaging of testicular tumours. Cancer Imaging 2005;4:S101–7. https://doi.org/10.1102/1470-7330.2004.0052.
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Marshall, C., Enzerra, M., Rahnemai-Azar, A.A. et al. Serum tumor markers and testicular germ cell tumors: a primer for radiologists. Abdom Radiol 44, 1083–1090 (2019). https://doi.org/10.1007/s00261-018-1846-z
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DOI: https://doi.org/10.1007/s00261-018-1846-z