As mentioned, serum alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH) play an important role in the diagnosis, prognosis, and follow-up assessment of patients in germ cell cancers [7, 8]. The interpretation of tumor marker levels in germ cell cancer management [9] has been refined for clinical application based on the results of multiple randomized clinical trials and will be discussed further in this section.

AFP is normally produced by the fetal yolk sac and therefore is essentially undetectable in normal adult males (normal levels in males 10–15 μg/l). As a tumor marker in germ cell cancers, it is observed to be elevated in yolk sac testicular tumors and embryonal carcinoma. Seminoma cells do not produce AFP, and therefore by definition, patients with germ cell tumors presenting with elevated AFP levels are treated as non-seminomatous germ cell tumors [9, 10].

In non-seminomas, elevated AFP levels can vary with stage of presentation as it is increased in 10–20 % with stage I disease, 20–40 % with low-volume stage II disease, and 40–60 % with advanced disseminated disease. The half-life of AFP is approximately 5–7 days [9], and, therefore, serum AFP should normalize 25–35 days (five half-lives) following effective treatment for a non-seminoma [9, 11, 12]. Failure to normalize can raise the suspicion of inadequately treated or ineffectively treated disease. There can be misleading false-positive reasons for elevated AFP levels in males. Benign liver conditions such as hepatitis, fatty liver disease, hepatocellular carcinoma, and other gastrointestinal malignancies can produce an elevation in AFP, and these should be kept in mind especially after patients have undergone localized or systemic treatments. In addition, tumor lysis during early chemotherapy could also produce a falsely positive result [9].

β-hCG is a common serum tumor marker for germ cell cancers. The serum concentration of β-hCG is elevated in approximately 15–20 % of patients with advanced pure testicular seminoma. In addition, 10–20 % of stage I, 20–30 % of low-volume stage II, and 40 % of advanced disseminated testicular non-seminomas present with an elevated serum β-hCG [9, 12]. The biologic half-life of β-hCG is approximately 1.5–3 days [9]. Therefore, during monitoring of treatment effect, serum β-hCG should normalize 1–2 weeks following effective treatment for a β-hCG-producing testicular cancer [9].

As with AFP, there can be false-positive reasons for elevated β-hCG levels other than germ cell tumors including in one report with the use of marijuana [13]. Other malignancies including neuroendocrine tumors, non-germ cell genitourinary cancers, lung cancer, and cancers of the female genital tract are also occasionally associated with elevated β-hCG levels. In addition, hypogonadism can also cause increased production of LH and hCG by the pituitary gland via the pituitary–gonadal axis feedback mechanism, thus leading to a falsely elevated serum β-hCG. Of note, this scenario could be observed after primary treatment of testicular cancer such as orchiectomy. Similar to the tumor lysis effect on AFP, β-hCG could also be falsely elevated during the first cycle of chemotherapy [9].