Testicular germ cell tumours (TGCTs), regarded as rare cancers, are increasing in frequency: over the last 30 years, their incidence in the UK has approximately doubled. Similar trends have been observed in multiple geographical locations.1 It has been suggested, however, that in some countries the number of cases may have plateaued in recent years and the incidence of the two main histological subtypes of TGCTs may be starting to diverge. With the development of platinum-based chemotherapy regimens in the last 30–40 years, this once fatal disease has become a model for curability in cancer, as disease-specific survival exceeds 98%.
As a curable malignancy, much effort in clinical research in TGCTs is directed towards identifying those patients in early-stage disease who need therapies that will prevent recurrence, sparing the burden of treatment toxicities for those who will not relapse, and tailoring treatments in advanced disease to minimize toxicities. Most patients may then survive TGCTs and live long and productive lives.
In the development of management strategies, a number of histological and biochemical factors have been identified that support these aims. They can be used to advise patients with different stages of disease on the most suitable management strategy for their disease that best suits their own physical and psychosocial characteristics.
A biomarker has been defined as: 'A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention'2 and 'Any substance, structure or process that can be measured in the body or its products and influences or predicts the incidence or outcome of disease.'3
This chapter outlines how biomarkers have revolutionized the management of TGCTs, making it a prime example of precision oncology. It explores how the traditional medical biomarkers derived from histological analysis and serum protein expression are being augmented, and potentially superseded, by novel molecular and genetic markers that will allow even greater precision in treatment selection and development.
Current biomarker-directed management of TGCTs
TGCTs are biologically complex malignancies that can demonstrate a number of histological patterns within both the primary tumour and the metastatic deposits that occur at distant sites in advanced disease. A full description of this classification is beyond the scope of this chapter. All TGCTs, however, are understood to derive from a common primordial germ cell.4 The clinical management of early-stage TGCTs is directed by the separation of seminomas from all other TGCTs (including those comprising seminomas mixed with other histological subtypes): these are referred to as non-seminomatous TGCTs (NSTGCTs). Seminomas have a different sensitivity to treatment with radiotherapy and chemotherapy compared with NSTGCTs. Different histological characteristics appear to predict relapse in early-stage seminomas compared with NSTGCTs following orchidectomy.
In early-stage NSTGCTs, tumour invasion of intratesticular blood and lymphatic vessels ...