The Past and Future of Biomarkers in Testicular Germ Cell Tumors

Abstract

Testicular germ cell tumor (GCT) is the most common malignancy in 18- to 40-year-old men. Unlike most other cancers, GCT is frequently curable even when metastatic. These tumors can be classified histologically into seminoma and non-seminoma, which determines treatment. Therefore, successful treatment requires accurate diagnosis, classification, and monitoring. Serum tumor markers, including lactate dehydrogenase, α-fetoprotein, and β-human chorionic gonadotropin, aid in the classification and staging of GCTs. These markers therefore play a critical role in the decision-making process when managing GCT patients. However, there exist many scenarios in which these markers fail to perform adequately. This is particularly true in the case of seminoma, where only 10% to 15% will have elevated serum tumor markers. Non-specific elevation of these markers is also a common occurrence, complicating the interpretation of borderline positive results, particularly in follow-up. To bridge this gap in performance, next generation biomarkers are being investigated. In this review, we consider the role of conventional serum tumor markers in GCT management and discuss recent advances in the next generation of biomarkers, with a focus on circulating microRNAs. We discuss the value that circulating microRNAs could bring as an addition to currently used markers, as well as potential weaknesses, in GCT management.