A stroll through the present and future of testicular germ cell tumour biomarkers

ABSTRACTIntroduction Testicular germ cell tumors (TGCT) are the most commonly diagnosed cancers among young men. Although these tumors usually have a good prognosis and are highly treatable, clinicians and pathologists still face specific dilemmas inherent to this tumor model, which is highly due to its developmental origin.Areas Covered A wide-ranging review of the currently available and future prospects in the field of TGCT biomarkers is presented.Expert Opinion The field of TGCT biomarkers has been widely studied in the last decade. Although these patients usually present with good prognosis, there are still specific clinical questions where novel biomarkers are needed to complement the ones already used in the clinic. These questions include the follow-up method of clinical stage-I patients, detection of minimal residual disease, proper identification of teratoma, and suitable selection of patients to chemotherapy, according to their inherent resistance.KEYWORDS: Testicular germ cell tumorsBiomarkersSerum tumor markersMiR-371a-3pliquid biopsieshistopathologyrisk stratificationDNA methylation Article highlights Tissue-derived biomarkers, including immunohistochemistry, and tumor morphology analysis are vital to properly diagnose and stage TGCT patients.TGCT classical serum biomarkers remain useful in the clinic but are limited due to lack of sensitivity and specificity.miR-371a-3p, the most promising next-generation liquid biopsy biomarker for TGCTs due to its high sensitivity and specificity, is in the final pre-analytical and standardization phase. miR-371a-3p will shortly enter clinical practice.Cell-free DNA methylation biomarkers show promise in addressing certain TGCT clinical dilemmas but are not yet ready to enter the fray due to analytical and technical questions.There is still a need for novel TGCT biomarkers that are able to answer specific medical challenges, including detection of teratoma.Declaration of interestThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewers disclosurePeer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.Additional informationFundingNuno Tiago Tavares holds a contract funded by Programa Operacional Regional do Norte and co-funded by European Regional Development Fund under the project 'The Porto Comprehensive Cancer Center', with the reference NORTE-01-0145-FEDER-072678 (Porto.CCC, Contract RNCCCP.CCC-CI-IPOP-LAB3). The authors would also like to acknowledge the support of 'Bolsa de Investigação Médica LPCC/Lions – Cancro Infantil' 2022.