Emerging Prognostic Biomarkers in Testicular Germ Cell Tumors: Looking Beyond Established Practice

Abstract

Testicular germ cell tumors are unique among solid cancers. Historically, this disease was deadly if progressed beyond the stage I. The implementation of cisplatin-based chemotherapy regimens has drastically changed the clinical outcome of metastatic testicular cancer. Several biomarkers were established to refine the prognosis by International Germ Cell Collaborative Group in 1997. Among these, the most significant were primary tumor site; metastatic sites, such as non-pulmonary visceral metastases; and the amplitude of serum tumor markers α-fetoprotein, β-chorionic gonadotropin, and lactate dehydrogenase. Since then, oncology has experienced discoveries of various molecular biomarkers to further refine the prognosis and treatment of malignancies. However, the ability to predict the prognosis and treatment response in germ cell tumors did not improve for many years. Clinical trials with novel targeting agents that were conducted in refractory germ cell tumor patients have proven to have negative outcomes. With the recent advances and developments, novel biomarkers emerge in the field of germ cell tumor oncology. This review article aims to summarize the current knowledge in the research of novel prognostic biomarkers in testicular germ cell tumors.

Immune mechanisms and possible immune therapy in testicular germ cell tumours

“…Biomarkers for novel treatments were virtually non‐existent until recently in GCTs (Chovanec et al ., ,,). Recent discoveries updated our knowledge on immune‐related biology of this disease.…”

“…Authors also combined SII with PD‐L1 expression on TILs to design a prognostic tool for GCT outcome. This tool recognized never relapsing and never dying patients and identified a poor prognostic group, where none of the relapsed patients were salvageable with treatment (Chovanec et al ., ,,). Simultaneously, Fankhauser et al ., () reported the same findings on SII together with the prognostic significance of neutrophils, neutrophil‐to‐lymphocyte ratio and c‐reactive protein.…”

“…WNT signalling is commonly activated in GCTs, especially in non‐seminomas, that possess lower TIL counts compared with seminomas. Active WNT evidenced by high expression of β‐catenin correlates with poor clinical characteristics of GCTs and PD‐L1 status on tumour cells and is involved in aberrant maturation, proliferation and function of T and B cells (Chovanec et al ., ,,). This finding may create a premise to consider WNT inhibition combined with immune checkpoint inhibitors as a promising treatment approach.…”

Molecular characteristics of testicular germ cell tumors: pathogenesis and mechanisms of therapy resistance

“…In US, the estimated incidence is 6.6 cases of whites and 1.2 cases of African Americans per 100,000 people annually. This incidence has increased over the past few decades; however, the mortality rate has significantly decreased due to the advances of treatment modalities especially the introduction of cisplatin-based chemotherapy [1,2].…”

“…In recent years, advancing molecular diagnostics has uncovered some potentially selective molecular targets for therapy, including SOX2, SOX17, HMGA1, HMGA 2, NEK2, Aurora B, PATZ1, and GPR30 [1,2]. However, despite the advances in research and treatment development, resistance to cisplatin-based chemotherapy has greatly impacted the otherwise favorable patients' outcome.…”