How to classify, diagnose, treat and follow-up extragonadal germ cell tumors? A systematic review of available evidence.

To present the current evidence and the development of studies in recent years on the management of extragonadal germ cell tumors (EGCT).

A systematic literature search was conducted in Medline and the Cochrane Library. Studies within the search period (January 2010 to February 2021) that addressed the classification, diagnosis, prognosis, treatment, and follow-up of extragonadal tumors were included. Risk of bias was assessed and relevant data were extracted in evidence tables.

The systematic search identified nine studies. Germ cell tumors (GCT) arise predominantly from within the testis, but about 5% of the tumors are primarily located extragonadal. EGCT are localized primarily mediastinal or retroperitoneal in the midline of the body. EGCT patients are classified according to the IGCCCG classification. Consecutively, all mediastinal non-seminomatous EGCT patients belong to the "poor prognosis" group. In contrast mediastinal seminoma and both retroperitoneal seminoma and non-seminoma patients seem to have a similar prognosis as patients with gonadal GCTs and metastasis at theses respective sites. The standard chemotherapy regimen for patients with a EGCT consists of 3-4 cycles (good vs intermediate prognosis) of bleomycin, etoposid, cisplatin (BEP); however, due to their very poor prognosis patients with non-seminomatous mediastinal GCT should receive a dose-intensified or high-dose chemotherapy approach upfront on an individual basis and should thus be referred to expert centers Ifosfamide may be exchanged for bleomycin in cases of additional pulmonary metastasis due to subsequently planned resections. In general patients with non-seminomatous EGCT, residual tumor resection (RTR) should be performed after chemotherapy.

In general, non-seminomatous EGCT have a poorer prognosis compared to testicular GCT, while seminomatous EGGCT seem to have a similar prognosis to patients with metastatic testicular seminoma. The current insights on EGCT are limited, since all data are mainly based on case series and studies with small patient numbers and non-comparative studies. In general, systemic treatment should be performed like in testicular metastatic GCTs but upfront dose intensification of chemotherapy should be considered for mediastinal non-seminoma patients. Thus, EGCT should be referred to interdisciplinary centers with utmost experience in the treatment of germ cell tumors.

World journal of urology. 2022 May 12 [Epub ahead of print]

Christian Winter, Friedemann Zengerling, Jonas Busch, Julia Heinzelbecker, David Pfister, Christian Ruf, Julia Lackner, Peter Albers, Sabine Kliesch, Stefanie Schmidt, Carsten Bokemeyer

Urological Practice "Urologie Neandertal", Erkrath, Germany. ., Department of Urology and Pediatric Urology, University Hospital of Ulm, Ulm, Germany., Department of Urology, Charité Universitaetsmedizin Berlin, Berlin, Germany., Department of Urology and Paediatric Urology, Saarland University Medical Centre, Faculty of Medicine, Saarland University, Homburg, Saar, Germany., Department of Urology, University Hospital Cologne, Cologne, Germany., Department of Urology, Bundeswehrkrankenhaus, Ulm, Germany., UroEvidence@Deutsche Gesellschaft Für Urologie, Berlin, Germany., Department of Urology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital, Münster, Münster, Germany., Department of Oncology, Hematology, BMT Plus Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.