Decoding testicular germ cell tumors: integrating risk, biology, and biomarkers into future care

Testicular germ cell tumors (TGCTs) are the most common cancer among young men of European ancestry. TGCT incidence is rising worldwide while risk factors remain elusive. Genomically, TGCTs have high aneuploidy, low somatic mutational burden, and are globally hypomethylated. TGCT genetics is polygenic, with 78 susceptibility loci identified from large genome-wide association studies. It is highly curable when utilizing multimodal therapy with cisplatin chemotherapy and surgical interventions. However, since patients can live many decades after cure, the long-term health consequences and psychosocial impacts caused by treatment must be considered. Recently, the microRNA cluster miR-371-3 and ctDNA have emerged as TGCT biomarkers with promising clinical utility. We review recent efforts on elucidating TGCT biology, identifying factors associated with risk, disease progression and recurrence, and treatment de-escalation to limit impacts on disease survivorship.