Narrative review of developing new biomarkers for decision making in advanced testis cancer

Management of testicular germ cell tumor (GCT) patients is based on clinical determinants, mainly CT scan and serum tumor markers (alpha-fetoprotein, beta subunit of HCG and LDH). Treatment decisions are usually straightforward for patients with clear evidence of metastatic disease, confirmed either by imaging tests or by unequivocal elevated tumor markers. However, there are several clinical scenarios where the assessment of metastatic disease is complicated by the limited specificity of the current imaging tests and serum tumor markers. These include patients with clinical stage IIA GCT with negative tumor markers and patients with post-chemotherapy residual disease where, in absence of clear indicators of GCT, decision making and patient treatment allocation become challenging. Therefore, more accurate biomarkers are critical to reduce the risk of under-or over-treatment and to always deliver the most optimal therapy. The objectives of this narrative review are to review the available publications about micro-RNAs in GCT s and their potential clinical applications. Two clusters of micro-RNAs, miR-371a-3p and miR-302/367, specifically expressed by both seminoma and non-seminoma GCT and easily detectable in the peripheral blood, have demonstrated to be promising in this endeavor. Large prospective trials are ongoing to define the operating characteristics of these biomarkers and their clinical utility to improve GCT patient management and reduce the error rate deriving from clinical uncertainty, therefore reducing the risk of sub-optimal treatments.