EAU 2018: New Molecular Tumor Markers for Germ Cell Tumors - Ready for Prime Time?

Copenhagen, Denmark (UroToday.com) Testis cancer has been one of few cancers (Prostate (PSA), Colon Cancer (CEA), Ovarian Cancer (CA19-9)) where serum biomarkers play a significant role in staging and in the assessment of treatment response. Unfortunately, the current biomarkers (AFP, HCG, and LDH) are only elevated in ~ 50% of cases and tend to be of minimal value in patients presenting with low stage disease. To date, we are in dire need for tumor-specific biomarkers that allow for better risk stratify patients, especially those with stage I disease, where overtreatment is a significant concern. Dr. Deickmann, from Hamburg, presents data on a novel microRNA based biomarker that is showing remarkable promise to become a testis cancer-specific biomarker. 

Small non-coding RNAs (miRNAs) are regulators of gene expression at the post-transcriptional level. Recently microRNAs have been found to play a pivotal role in the process of malignant transformation of several cancers. MicroRNAs show great potential as novel biomarkers because of their high stability in body fluids, and their relative ease of detection by standard quantitative reverse transcriptase polymerase chain reaction assays (rtPCR). The role of microRNAs in testis cancer was originally published by a group from Cambridge (Am. J. Clin. Pathol. 2011) where microRNA 371-372 and 302 were able to be detected in a single patient with testis cancer and tracked through treatment with excellent correlation with known tumor markers (AFP and bHCG). In a prospective study by the speaker (BCJ 2012), serum levels of miRNA-371 to -373 from 24 patients with testis cancer (20 seminomas, four non-seminomatous tumors) were evaluated. Out of the three miRNAs quantified, miR-371a-3p showed the most impressive detection accuracy. In this study, 20 patients presented with clinical stage I disease. Only 25% showed elevation of the classical markers (AFP and bHCG), whereas 85% of patients had a higher level of miRNA-371a-3p when compared to healthy controls 

In a validation study by Gillis et al. (Mol Path 2013). the serum levels of miR-371 to -373, miR-302 and miR-367 measured in 80 patients with testis cancer and compared to 47 healthy controls. miR-371 to - 373 and miR-367 showed the most promising results in regard to cancer detection. By combining these miRNAs, a clear separation of testis cancer from control samples was possible with an overall sensitivity of 98%, whereas the traditional serum markers (AFP and bHCG) revealed only a sensitivity of 36% and 57%, respectively. 

The level of miR-371a-3p has also been able to be correlated with chemotherapy response in patients with advanced stage disease. Following the level of miR-371a-3p, the researchers were able to predict responders, failures and early recurrences. The group from Toronto recently reported the use of miRNA for the detection of viable tumor in patients with residual post-chemotherapy masses. In their evaluation miR-371a-3p was able to predict viable tumor with AUC of 0.85. 

In summary, novel miRNA serum biomarkers appear to be over-performing to classical tumor makers in prediction of treatment response (local or systemic), rapid recurrence and treatment failure. While further validation will be necessary, miRNA biomarkers appear to be the future for improved disease and treatment stratification. 

Presented by: Klaus-Peter Dieckmann MD, Hamburg, Germany

Written by: Andres F. Correa, Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark.