ESOU 2019: Molecular Markers for Staging and Monitoring Testis Cancer

Prague, Czech Republic (UroToday.com) Testicular cancer staging and monitoring has historically relied on imaging and serum tumor markers. However, recently, there has been increasing interest in molecular markers in the testis cancer disease space.  Dr. Arlo Radtke from Germany discussed new molecular markers on the horizon for testis cancer patients.

Dr. Radtke notes that the problem with the classic serum tumor markers (beta-HCG, LDH, and alpha-fetoprotein) is that they are only elevated in a subset of patients. Through the work of several international groups over the last several years, the embryonic miRNA cluster miR-302 and miR-371-3 have emerged as potential biomarkers for monitoring and staging testis cancer 1

For the remainder of his presentation, Dr. Radtke presented the results of his European multicentric study. This study comprised 616 patients and 258 control patients recruited from 37 institutions from Germany, Austria, Switzerland, Italy, and Hungary. The primary objective was to analyze the impact of miR-371a-3p serum levels in these patients, based on previous work from Dr. Radtke and his group2. Preoperatively, miR-371a-3p had significantly lower expression in controls than in tumor samples (p<0.001), with increasingly higher expression with more advanced disease. Second, there was a significantly higher expression in CS1 nonseminoma than in CS1 seminoma, although there was no difference based on histology when comparing CS2 and CS3 tumors. When looking at specific tumor subtypes for CS1 patients, there was low to no miR-371a-3p expression in teratoma and otherwise higher expression in the other nonseminoma subtypes than in seminoma tumors.

The following discriminative parameters were reported by Dr. Radtke:

  • GCT (n=522) vs controls (n=258): AUC 0.97, sensitivity 91.8%, specificity 96.1%
  • CS1 (n=371) vs controls (n=258): AUC 0.958, sensitivity 88.9%, specificity 96.1%
  • CS2/CS3 (n=151) vs controls (n=258): AUC 0.998, sensitivity 98.7%, specificity 96.1%
In all groups (GCT, NSGCT, seminoma, CS1, and CS2/CS3) assessed, miR-371a-3p was more sensitive than the classic serum tumor markers by themselves or combined. Additionally, miR-371a-3p showed a 59% sensitivity for seminomas <1 cm, but there was no association for NSGCT tumor diameter. miR-371a-3p levels decreased in 91.8% of CS1 patients after treatment and in 82.4% of CS2/CS3 patients. Specific to monitoring CS2/CS3 patients during chemotherapy, miR-371a-3p decreased after the first cycle among CS2 patients, and after the first and second cycle among CS3 patients. With regards to detection of relapse, miR-371a-3p was significantly higher during relapse with a sensitivity of 82.6%, and subsequent decline after treatment of the relapse.

Dr. Radtke concluded with the following concluding remarks for miR-371a-3p:

  • Very high sensitivity and specificity in the primary diagnosis of testis cancer
  • Elevated in all histological subtypes except teratoma
  • Superior to classical serum tumor markers
  • Useable in treatment monitoring
  • Elevated at relapse, with a subsequent decline after treatment

Presented by: Arlo Radtke, Ph.D., Center for Human Genetics and Genetic Counselling (ZHG), The University of Bremen, Bremen, Germany

Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic

References:
  1. Leao R, van Agthoven T, Figueiredo A, et al. Serum miRNA predicts viable disease after chemotherapy in patients with testicular nonseminoma germ cell tumor. J Urol 2018 Jul;200(1):126-135.
  2. Dieckmann KP, Radtke A, Spiekermann M, et al. Serum levels of microRNA miR-371a-3p: A sensitive new biomarker for germ cell tumors. Eur Urol 2017 Feb;71(2):213-220.
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