While miRNAs have not demonstrated to be easy therapeutic targets, growing evidence suggests that they are reliable diagnostic biomarkers in germ cell tumors (GCTs). GCTs are embryonally and biologically very distinct from other solid malignancies and retain most of the embryonal stem cells characteristics, including expression of a specific subset of miRNAs. miR371a-3p (miR371) has high accuracy to identify active germ cell malignancy (aGCM) in both seminoma and nonseminoma GCTs. In order to move this biomarker forward into the clinical practice, 2 clinical trials have been designed and are currently accruing patients in the pediatric (AGCT-1531) and adult GCT populations (S1823). S1823 is a SWOG-lead cohort trial that has the objective to prospectively and clinically validate miR371 in adult GCT. Taking advantage of our group leader position in S1823, we are proposing to utilize the plasma miR371 expression data and the radiologic images coupled with clinical data collected for S1823 to create a biologicalclinical predictive model of aGCM in patients with early stage GCT on surveillance. Hypothesis. miR371 has higher PPV than standard of care clinical tools to identify aGCM in early stage germ cell tumors and it can be used to identify tumor relapse earlier and with more accuracy. Aims. The aims of this research project are to: 1. Measure plasma miR371 expression in S1823 specimens at baseline and during the follow-up. 2. Integrate/compare the qualitative and quantitative miR371 expression with the clinical annotation as detailed in the S1823 trial design. Methods. The baseline and the serial samples collected during the surveillance from the patients enrolled in S1823 will be analyzed for miR371 expression using RT-PCR. The CT scan images data collected at the same time point of miR371 will be compared to miR371 expression for the determination of the PPV, NPV, sensitivity and specificity. The accuracy of the tests individually or combined will be analyzed to define the AUC of the ROC and to create a predictive model of aGCM that integrates clinical and biological data. Innovation. The innovation of this research proposal resides neither in the quite basic and universal RT-PCR technique used for the miR371 expression, nor in the simple statistic and study design. The innovation consists in the potential clinical utilization of this highly specific biological marker for early detection of aGCM which will open more opportunities for replacement or integration of conventional images, treatment de-escalation and personalization on the base of biological rather than clinical evidence of GCTs. Significance and impact: Early and more accurate identification of aGCM during surveillance has the potential to reduce treatment burden of the young GCT patients’ population and to prevent long term side effects of chemo and radiation treatments with meaningful improvement of GCT patients’ quality of life.