The key application of serum tumor markers in testicular cancer: a review and update

Kishore G. Banerjee, Muhammad Haziq A. Shamsul Azlan, Logeswaran Kalaiarasu, Haifa S. Hasrol Nizam


Testicular neoplasm is the most common solid tumor in male. The recent advancement in the medical field has made it possible to become one of the most highly treatable neoplasms. Testicular neoplasm is mainly classified into two main groups: non-seminomatous germ cell tumor and seminomatous germ cell tumor. In this review article, we analyzed the current role of serum biomarkers in diagnosis, prognosis, staging, measurement of response to therapy and early detection of relapse of testicular neoplasm. The commonly used tumor markers are alpha-fetoprotein (AFP), beta-human chorionic gonadotrophins and lactate dehydrogenase. Apart from them, a new set of tumor biomarkers like placental­like alkaline phosphatase, gamma­glutamyltranspeptidase, miRNA, mitochondrial DNA and serum trace elements are also proven to be potentially helpful in the management of testicular neoplasm. Progressive elevation of serum tumor markers often indicates the presence of testicular cancer and aids in histological classifications. According to an additional category, the rate of elevation of respective biomarkers is advantageous to appropriately stage testicular neoplasm (S) in the tumor nodes metastases (TNM) staging classification. Besides, it is found that higher elevation of serum tumor markers is associated with a poorer prognosis. Post-treatment assessment where there is a rate of reduction of serum tumour biomarkers suggests the effectiveness of initial management of testicular neoplasm.


Tumor markers, Lactate dehydrogenase, Alpha-fetoprotein, β-human chorionic gonadotropin, Seminoma, Non-seminomatous germ cell tumor

Full Text:



Park JS, Kim J, Elghiaty, Ham WS. Recent global trends in testicular cancer incidence and mortality. Med. 2018;97(37):12390.

Winter C, Albers P. Testicular germ cell tumours: Pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2011;7(1):43-53.

Marshall C, Enzerra M, Rahnemai-Azar AA, Ramaiya NH. Serum tumour markers and testicular germ cell tumours: a primer for radiologists. Abdom Radiol. 2019;44:1083-90.

Leão R, Ahmad AE, Hamilton RJ. testicular cancer biomarkers: a role for precision medicine in testicular cancer. Clin Genitourin Cancer. 2019;17(1):176-83.

Forman D, Oliver RTD, Brett AR, Marsh SGE, Moses JH, Bodmer JG, et al. Familial testicular cancer: A report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Br J Cancer. 1992;65(2):255-62.

Motzer RJ, Agarwal N, Beard C, Bolger GB, Boston B, Carducci MA. et al. Testicular cancer. J Comprehen Cancer Net. 2009;7(6):672-93.

Stevenson SM, Lowrance WT. Epidemiology and diagnosis of testis cancer. Urol Clin North Am. 2015;42(3):269-75.

Smith ZL, Werntz RP, Eggener SE. Testicular cancer: epidemiology, diagnosis, and management. Med Clin North Am. 2018;102(2):251-64.

Ulaganathan V, Kandiah M, Shariff ZM. A case-control study on the association of abdominal obesity and hypercholesterolemia with the risk of colorectal cancer. J Carcinog. 2018;17:4.

Rajendran P, Alzahrani AM, Hanieh HN, Kumar SA, BenAmmar R, Rengarajan T, et al. Autophagy and senescence: a new insight in selected human diseases. J Cell Physiol. 2019;234(12):1-8.

Buljubašić R, Buljubašić M, Bojanac AK, Ulamec M, Vlahović M, Ježek D, et al. Epigenetics and testicular germ cell tumors. Gene. 2018;661:22-33.

Ahmed HU, Arya M, Muneer A, Mushtaq I, Sebire NJ. Testicular and paratesticular tumours in the pre-pubertal population. Lancet Oncol. 2010;11(5):476-83.

Masterson TA, Rice KR, Beck SDW. Current and future biologic markers for disease progression and relapse in testicular germ cell tumours: a review. Urol Oncol Semin Orig Investig. 2014;32(2):261-71.

Wahed A, Dasgupta A. Pitfalls in testing for common tumour markers. Accur Result Clinic Lab. 2019.

Barlow LMJ, Badalato GM, McKiernan JM. Serum tumour markers in the evaluation of male germ cell tumours. Nat Rev Urol. 2010;7(11):610-7.

Pearson JC, Spaulding JT, Friedman MA. Testicular cancer: role of biological tumour markers. Cancer Treat Rev. 1979;6(4):217-21.

Ehrlich Y, Beck SDW, Foster RS, Bihrle R, Einhorn LH. Serum tumor markers in testicular cancer. Urol Oncol Semin Orig Investig. 2013;31:17-23.

Mir MC, Pavan N, Gonzalgo ML. Current clinical applications of testicular cancer biomarkers. Urol Clin North Am. 2016:43(1):119-25.

Arifin TK, Sulaiman S, MdSaad S, Damanhuri AH, WanNgah WZ, Mohd YA. Elevation of tumour markers TGF-β, M2-PK, OV-6 and AFP in hepatocellular carcinoma (HCC)-induced rats and their suppression by microalgae Chlorella vulgaris. BMC Cancer. 2017;17:879.

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.

Takizawa A, Kishida T, Miura T, Hattori Y, Noguchi K, Kubota Y. Clinical significance of low-level human chorionic gonadotropin in the management of testicular germ cell tumor. J Urol. 2008;179(3):930-5.

Nielsen OS, Munro AJ, Duncan W, Sturgeon J, Gospodarowicz MK, Jewett MAS, et al. Is placental alkaline phosphatase (PLAP) a useful marker for seminoma? Eur J Cancer Clin Oncol. 1990;26(10):1049-54.

Javadpour N. Multiple biochemical tumour markers in seminoma: a double‐blind study. Cancer. 1983;52(5):887-9.

Kaba M, Pirinççi N, Yüksel MB, Gecit I, Güneş M, Demir M, et al. Serum levels of trace elements in patients with testicular cancers. Int Braz J Urol. 2015;41(6):1101-7.

Murray MJ, Huddart RA, Coleman N. The present and future of serum diagnostic tests for testicular germ cell tumours. Nat Rev Urol. 2016;13(12):715-25.

Ruf CG, Khalili-Harbi N, Sachs S, Isbarn H, Wagner W, Matthies C, et al. The search for biomarkers of metastatic seminoma. J Urol. 2013;190(3):1046-51.

Horwich A, Nicol D, Huddart R. Testicular germ cell tumours. BMJ. 2013;347:1-9.

Dieckmann K, Simonsen-Richter H, Kulejewski M, Anheuser P, Zecha H, Isbarn H, et al. Serum tumour markers in testicular germ cell tumours: frequencies of elevated levels and extents of marker elevation are significantly associated with clinical parameters and with response to treatment. Biomed Re Int. 2019.

Cheng L, Albers P, Berney DM, Feldman DR, Daugaard G, Gilligan T, et al. Testicular cancer. Nat Rev Dis Prim. 2018;4(1):29.

Salem M, Gilligan T. Serum tumor markers and their utilization in the management of germ-cell tumors in adult males. Expert Rev Anticancer Ther. 2011;11(1):1-4.

Javadpour, N. The role of biologic tumor markers in testicular cancer. Cancer. 1980;45:1755-61.

Pectasides D, Pectasides E, Constantinidou A, Aravantinos G. Current management of stage I testicular non-seminomatous germ cell tumours. Crit Rev Oncol Hematol. 2009;70(2):114-23.

Al-Naggar RA, Bobryshev YV, Abdulghani MAM, Rammohan S, Al-Jashamy K. Knowledge and perceptions of cancer and cancer prevention among Malaysian traditional healers: a qualitative study. Asian Pacific J Cancer Prev. 2012;13(8):3841-50.

Venkitaraman R, Johnson B, Huddart RA, CC, Horwich A, Dearnaley DP. The utility of lactate dehydrogenase in the follow-up of testicular germ cell tumours. BJU Int. 2007;100(1):30-2.

Alifrangis C, Lucas O, Benafif S, Ansell W, Greenwood M, Smith S. Management of late relapses after chemotherapy in testicular cancer: optimal outcomes with dose-intense salvage chemotherapy and surgery. Eur Urol Focus. 2020;4(20):1-8.

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(3):557-9.

Regouc M, Belge G, Lorch A, Dieckmann K, Pichler M. Non-coding microRNAs as novel potential tumor markers in testicular cancer. Cancers (Basel). 2020;12(3):1-16.

Terbuch A, Adiprasito JB, Stiegelbauer V, Seles M, Klec C, Pichler GP, et al. Mir-371a-3p serum levels are increased in recurrence of testicular germ cell tumor patients. Int J Mol Sci. 2018;19(10):3130.