SUO 2019: Serum microRNA-371a-3p Levels Predict Viable Germ Cell Tumor in Chemotherapy-Naïve Patients Undergoing Retroperitoneal Lymph Node Dissection

Washington, DC ( The clinical utility of current serum tumor markers (alpha-fetoprotein, beta-HCG, and LDH) for testis cancer is limited by the lack of sensitivity and specificity. As such, there is an unmet need in this space for identifying biomarkers that can better guide treatment decision making. Serum microRNAs are candidate biomarkers for diagnosing and monitoring germ cell tumors,1, 2 however, the ability of miRNA to inform treatment in low-stage chemotherapy-naïve patients is previously unexplored.  Dr. Nirmish Singla presented their group's results evaluating the performance characteristics of serum miRNA levels to predict viable germ cell tumor in chemotherapy-naïve patients undergoing primary retroperitoneal lymph node dissection (RPLND).

This study prospectively collected presurgical serum samples and clinicopathologic characteristics from consecutive chemotherapy-naïve GCT patients undergoing primary RPLND from 2016-2019. Serum miRNAs (-367-3p/-371a-3p/-372-3p/-373-3p/-375) were isolated and quantified, and RPLND histopathology was categorized as benign, viable GCT, or teratoma. Between these histological groups, miRNA levels were compared. Performance characteristics, including receiver operating characteristic (ROC) curves, assessed the discriminative ability of each miRNA signature to predict viable GCT.  

There were 24 patients with stage I-II germ cell tumors (50% stage I, 50% stage II) that underwent RPLND, revealing viable GCT in 11 (46%) patients, teratoma in 3 (13%) patients, and benign pathology in 10 (42%) patients. miR-371a-3p was the most discriminatory serum miRNA for viable germ cell tumor, exhibiting ~13,000-fold increase in expression over teratoma or benign pathology:

SUO 2019 expression over teratoma or benign pathology

On ROC analysis, miR-371a-3p had an AUC of 0.965, a sensitivity of 100% and specificity of 92%. The AUC for other serum miRNAs in predicting viable GCT were 0.874 (miR-367-3p), 0.846 (miR-372-3p), and 0.720 (miR-373-3p). However, these serum miRNAs were not predictive of pure teratoma. A summary of the findings are as follows:

SUO 2019 serum miRNAs

Dr. Singla concluded with the following points from this study of miRNA in chemotherapy-naïve patients:

  • Serum miRNAs, particularly miR-371a-3p, can accurately differentiate small-volume viable GCT from benign processes or teratoma in patients with negative serum tumor markers undergoing primary RPLND
  • If validated, these data suggest a basis to implement precision medicine strategies in treating patients with early-stage GCT
  • Work is ongoing in collecting post-RPLND serum specimens for analysis

Presented by: Nirmish Singla, MD, Assistant Instructor/Fellow, Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, Texas

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md, at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC

1. Murray MJ, Halsall DJ, Hook CE, et al. Identification of microRNAs from the miR-371-373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am J Clin Pathol 2011;135:119-125
2. Dieckmann KP, Radtke A, Geczi L, et al. Serum levels of microRNA-371a-3p (M371 test) as a new biomarker of testicular germ cell tumors: Results of a prospective multicentric study. J Clin Oncol 2019;37:1412-1423.