Ricardo Leão1, Maarten Albersen2, Leendert H J Looijenga3, Torgrim Tandstad4, Christian Kollmannsberger5, Matthew J Murray6, Stephane Culine7, Nicholas Coleman8, Gazanfer Belge9, Robert J Hamilton10, Klaus-Peter Dieckmann11. 1. Department of Urology, Hospital de Braga, Hospitais CUF, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 2. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 3. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. 4. The Cancer Clinic, St. Olav's University Hospital, Trondheim, Norway. 5. Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, Canada. 6. Department of Pathology, University of Cambridge, Cambridge, UK; Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Cambridge, UK. 7. Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Paris, France; Paris-Diderot University, Paris, France. 8. Department of Pathology, University of Cambridge, Cambridge, UK; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 9. Faculty of Biology and Chemistry, University of Bremen, Bremen, Germany. 10. Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, Canada. 11. Department of Urology, Asklepios Klinik Altona, Hamburg, Germany. Electronic address: dieckmannkp@t-online.de.
Abstract
CONTEXT: Clinical management of testicular germ cell tumours (GCTs) is hampered by low sensitivity and specificity of the biomarkers currently in use. Circulating microRNAs (miRs) might offer the potential to address areas of unmet clinical need. OBJECTIVE: To systematically evaluate the evidence for clinical applications of serum levels of miR302/367 and miR371-3 in adult testicular GCTs in terms of primary diagnosis, various clinical scenarios, and the costs of clinical implementation. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase and the Cochrane Library in January 2021 in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. EVIDENCE SYNTHESIS: Thirty-one manuscripts addressed miR performance and potential clinical use in testicular GCT. Of these, 23 evaluated the utility in primary diagnosis, seven in early-stage disease, and 13 in metastatic disease, and two addressed the costs of clinical implementation. Of the various miRs studied, miR-371a-3p appears the most useful and potentially the only one that needs to be assayed, with an area under the receiver operating characteristic curve >0.90, sensitivity of 89-96%, and specificity of >90% for both seminoma and nonseminoma, surpassing the classic serum tumour markers. The miRs studied to date are not elevated in cases with teratoma only. Levels of miR-371a-3p correlate with primary tumour mass, clinical stage, and International Germ Cell Cancer Collaborative Group risk groups. Serial measurements mirror treatment efficacy in all clinical stages. CONCLUSIONS: Circulating miRNA levels, particularly of miR-371a-3p, have potential for incorporation in clinical practice and may aid in clinical decision-making in various clinical scenarios in GCT. PATIENT SUMMARY: We analysed the current evidence on the usefulness of blood levels of molecules called microRNAs in the management of testicular tumours. The microRNA-371a-3p molecule has better sensitivity and specificity than the markers currently being measured. This new biomarker may soon have a place in clinical practice.
CONTEXT: Clinical management of testicular germ cell tumours (GCTs) is hampered by low sensitivity and specificity of the biomarkers currently in use. Circulating microRNAs (miRs) might offer the potential to address areas of unmet clinical need. OBJECTIVE: To systematically evaluate the evidence for clinical applications of serum levels of miR302/367 and miR371-3 in adult testicular GCTs in terms of primary diagnosis, various clinical scenarios, and the costs of clinical implementation. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase and the Cochrane Library in January 2021 in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. EVIDENCE SYNTHESIS: Thirty-one manuscripts addressed miR performance and potential clinical use in testicular GCT. Of these, 23 evaluated the utility in primary diagnosis, seven in early-stage disease, and 13 in metastatic disease, and two addressed the costs of clinical implementation. Of the various miRs studied, miR-371a-3p appears the most useful and potentially the only one that needs to be assayed, with an area under the receiver operating characteristic curve >0.90, sensitivity of 89-96%, and specificity of >90% for both seminoma and nonseminoma, surpassing the classic serum tumour markers. The miRs studied to date are not elevated in cases with teratoma only. Levels of miR-371a-3p correlate with primary tumour mass, clinical stage, and International Germ Cell Cancer Collaborative Group risk groups. Serial measurements mirror treatment efficacy in all clinical stages. CONCLUSIONS: Circulating miRNA levels, particularly of miR-371a-3p, have potential for incorporation in clinical practice and may aid in clinical decision-making in various clinical scenarios in GCT. PATIENT SUMMARY: We analysed the current evidence on the usefulness of blood levels of molecules called microRNAs in the management of testicular tumours. The microRNA-371a-3p molecule has better sensitivity and specificity than the markers currently being measured. This new biomarker may soon have a place in clinical practice.
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