microRNA-371 during Follow-Up Protocol of Men with Localised Testicular Germ Cell Tumors - Beyond the Abstract

Background: The majority of men with testicular germ-cell tumours (GCTs) present with localised disease. After removal of the testis, a strict surveillance programmes with repeated measurements of the serum tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) is required. However, those serum markers only detect around half of all non-seminoma and the minority of seminoma relapses.1

Therefore, imaging being either computerized tomography (CT) or magnetic resonance imaging (MRI) is required. As the use of CT leads to radiation exposure in this young patient population as well as costs, alternative ways to detect of recurrence are required. Serum microRNA-371 is a new blood-based biomarker predicting visible GCT recurrence with the exception of pure teratomatous GCT.2 Based on previous studies, microRNA-371 could be an ideal biomarker for early and reliable detection of recurrences in men undergoing active surveillance of stage I GCT.

Methods & Results: Between April 2019 and January 2021 our group has prospectively collected 143 serum samples of 33 men with stage 1 GCT in the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS; NCT02229916).3 Follow-up and treatment were not influenced by this serum collection and we retrospectively analysed those samples.4 All 10 men with recurrence would have been detected by serum microRNA-371 at median of 2 months (range 0–5) earlier than the standard follow-up investigations (imaging, AFP, and HCG).

Conclusion & Way forward to move from bench to bedside: Increasing serum microRNA-371 levels during follow-up reliably predicted disease recurrence in all relapsing patients. Furthermore, recurrences were detected up to five months earlier compared to the standard follow-up investigations, and microRNA-371 levels remained undetectable in all but one patient without recurrence.

The high diagnostic accuracy of microRNA-371 to detect or rule out disease recurrence has the potential to significantly change the management of patients undergoing surveillance after orchiectomy. Because of limited data about the diagnostic accuracy and potential false-positive findings in the surveillance setting, the initiation of treatment solely based on serum microRNA-371 can currently not be justified and further clinical studies are required.

Several important questions remain before microRNA-371 can be used in the daily clinical routine. At the moment we do not have compelling data that microRNA-371 can replace follow-up imaging at all or that which cut-off value a microRNA-371 rise is confirmatory for relapse. Further, it remains unclear, whether disease recurrence, detected at an earlier time point might be suitable for less intense local (radiotherapy, surgery) or systemic (1-2 chemotherapy cycles) therapy.

Written by: Christian Daniel Fankhauser, MD, MPH, Lucerner Kantonsspital, Lucerne, Switzerland

References:

  1. Kollmannsberger C, Tandstad T, Bedard PL, Cohn-Cedermark G, Chung PW, Jewett MA, et al. Patterns of Relapse in Patients With Clinical Stage I Testicular Cancer Managed With Active Surveillance. J Clin Oncol. 2014.
  2. Almstrup K, Lobo J, Mørup N, Belge G, Rajpert-De Meyts E, Looijenga LH, et al. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours. Nature Reviews Urology. 2020:1-13.
  3. Rothermundt C, Thurneysen C, Cathomas R, Müller B, Mingrone W, Hirschi-Blickenstorfer A, et al. Baseline characteristics and patterns of care in testicular cancer patients: first data from the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS). Swiss medical weekly. 2018;148:w14640.
  4. Fankhauser CD, Christiansen AJ, Rothermundt C, Cathomas R, Wettstein MS, Grossmann NC, et al. Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours. British journal of cancer. 2021.

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