Developing a Highly Specific Biomarker for Germ Cell Malignancies: Plasma miR371 Expression Across the Germ Cell Malignancy Spectrum.

PURPOSE: Our objective was to evaluate operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumor. PATIENTS AND METHODS: One hundred eleven male patients with a history of or newly diagnosed germ cell tumors were evaluable. Biospecimens obtained before confirmed clinical events were analyzed for miR371 expression with blinding of providers and laboratory personnel to analytic results or clinical status, respectively. Cases (patients with clinically confirmed active germ cell malignancy [aGCM]) and controls (patients with no clinically confirmed aGCM) were assigned over the course of the management. Patients were assigned risk status (high, low, or moderate) based on the composite clinical picture at time points in management. RESULTS: Considering all cases and controls and results of prospectively obtained biosamples analyzed for miR371 expression, 46 (35%) of 132 samples had clinically confirmed aGCM over the course of management; 44 (96%) of these 46 patients had plasma miR371 expression (true positives) with no false positives. Two (4%) of 46 patients had no miRNA expression despite pathologic confirmation of aGCM (false negatives). Plasma miR371 expression in confirmed aGCM had a specificity, sensitivity, positive predictive value, and negative predictive value of 100%, 96%, 100%, and 98%, respectively. Interpretation of sensitivity and negative predictive value is limited by modest follow-up. Specificity and sensitivity were 100% and 98%, 100% and 92%, and 100% and 97% in the low-, moderate-, and high-risk groups, respectively, with a median follow-up time of 15 months. CONCLUSION: Plasma miR371 expression predicts aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 await longer follow-up for more complete definition, the findings of a highly specific liquid biopsy strongly support moving forward with large-scale, real-world clinical trials to further define full operating characteristics and to identify clinical utility and areas of patient benefit.

Should Small Renal Masses Be Biopsied?

Over the last few decades, the incidence of renal cell carcinomas (RCCs) has been steadily increasing. This is primarily due to an increase in detection of small renal masses (SRMs) as a result of widespread utilization of abdominal imaging. Interestingly, up to 30% of incidentally discovered SRMs (solid lesions measuring ≤4 cm) are benign, and consequently, the definitive treatment of all SRMs is associated with a considerable risk of overtreatment. To decrease the overtreatment rate, renal tumour biopsy (RTB) has been advocated as a safe alternative to identify the pretreatment histology of these SRMs. Although initially fraught with high non-diagnostic rates, more recent series from centres of experience have demonstrated that RTB is safe, reliable and accurate. The future of SRM management will combine pathological, molecular and genetic information to improve our ability to predict the behaviour of these lesions and herald risk-adapted personalized treatment.

The role of biopsy for small renal masses.

The incidence of small renal masses (SRMs) has been increasing due to the more liberal use of abdominal imaging. This increased detection has driven the attention of clinicians to the characterization of these lesions and toward a better understanding of their natural history. To this end, renal tumour biopsies (RTBs) have a crucial role as they provide vital pathological information. The improved quality and accuracy of RTBs provide urologists with a very truthful tool to support and guide treatment decisions. The future of RTB will combine pathological, molecular and genetic information that will, improve our knowledge about these lesions and open the potential for risk-adapted personalized medicine.

Indications for biopsy and the current status of focal therapy for renal tumours.

The increased detection of small renal masses (SRMs) has focused attention on their uncertain natural history. The development of treatment alternatives and the discovery of biologically targeted drugs have also raised interest. Renal mass biopsies (RMBs) have a crucial role as they provide the pathological, molecular and genetic information needed to classify these lesions and guide clinical management. The improved accuracy has improved our knowledge of the behaviour of different tumour histologies and opened the potential for risk-adapted individualized treatment approaches. To date, studies have demonstrated that percutaneous ablation is an effective therapy with acceptable outcomes and low risk in the appropriate clinical setting. Although partial nephrectomy (PN) is still considered the standard treatment for SRM, percutaneous ablation is increasingly being performed and if long-term efficacy is sustained, it may have a wider application for SRMs after biopsy characterization.