David Pfister1,2, Karin Oechsle3, Stefanie Schmidt4, Jonas Busch5, Carsten Bokemeyer3, Axel Heidenreich6, Julia Heinzelbecker7, Christian Ruf8, Christian Winter9, Friedemann Zengerling10, Sabine Kliesch11, Peter Albers12, Christoph Oing3,13. 1. Department of Urology, University Hospital Cologne, Cologne, Germany. David.pfister@uk-koeln.de. 2. Department of Urology, Uro-Oncology and Robot Assisted Surgery, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. David.pfister@uk-koeln.de. 3. Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Eppendorf, Hamburg, Germany. 4. UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Germany. 5. Department of Urology, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany. 6. Department of Urology, University Hospital Cologne, Cologne, Germany. 7. Department of Urology and Paediatric Urology, Saarland University Medical Centre and Saarland University Faculty of Medicine, Homburg, Saar, Germany. 8. Department of Urology, Bundeswehrkrankenhaus (Armed Forces Hospital, Ulm), Ulm, Germany. 9. Urologie Neandertal (Regional Joint Practice), Erkrath, Germany. 10. Department of Urology, University Hospital Ulm, Ulm, Germany. 11. Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University Hospital Muenster, Muenster, Germany. 12. Department of Urology, Medical Faculty, University Hospital Duesseldorf, Heinrich Heine University, Duesseldorf, Germany. 13. Mildred Scheel Cancer Career Center HaTriCs4, University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany.
Abstract
PURPOSE: In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. METHODS: This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. RESULTS: Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10-15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. CONCLUSIONS: Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients' survival.
PURPOSE: In this review, we summarize and discuss contemporary treatment standards and possible selection criteria for decision making after failure of adjuvant or first-line cisplatin-based chemotherapy for primarily localized or metastatic germ cell tumors. METHODS: This work is based on a systematic literature search conducted for the elaboration of the first German clinical practice guideline to identify prospective clinical trials and retrospective comparative studies published between Jan 2010 and Feb 2021. Study end points of interest were progression-free (PFS) and overall survival (OS), relapse rate (RR), and/or safety. RESULTS: Relapses of clinical stage I (CS I) patients irrespective of prior adjuvant treatment after orchiectomy are treated stage adapted in accordance for primary metastatic patients. Surgical approaches for sole retroperitoneal relapses are investigated in ongoing clinical trials. The appropriate salvage chemotherapy for metastatic patients progressing or relapsing after first-line cisplatin-based chemotherapy is still a matter of controversy. Conventional cisplatin-based chemotherapy is the international guideline-endorsed standard of care, but based on retrospective data high-dose chemotherapy and subsequent autologous stem cell transplantation may offer a 10-15% survival benefit for all patients. Secondary complete surgical resection of all visible residual masses irrespective of size is paramount for treatment success. CONCLUSIONS: Patients relapsing after definite treatment of locoregional disease are to be treated by stage-adapted first-line standard therapy for metastatic disease. Patients with primary advanced/metastatic disease failing one line of cisplatin-based combination chemotherapy should be referred to GCT expert centers. Dose intensity is a matter of ongoing debate, but sequential high-dose chemotherapy seems to improve patients' survival.
Authors: Sabine Kliesch; Stefanie Schmidt; Doris Wilborn; Clemens Aigner; Walter Albrecht; Jens Bedke; Matthias Beintker; Dirk Beyersdorff; Carsten Bokemeyer; Jonas Busch; Johannes Classen; Maike de Wit; Klaus-Peter Dieckmann; Thorsten Diemer; Anette Dieing; Matthias Gockel; Bernt Göckel-Beining; Oliver W Hakenberg; Axel Heidenreich; Julia Heinzelbecker; Kathleen Herkommer; Thomas Hermanns; Sascha Kaufmann; Marko Kornmann; Jörg Kotzerke; Susanne Krege; Glen Kristiansen; Anja Lorch; Arndt-Christian Müller; Karin Oechsle; Timur Ohloff; Christoph Oing; Ulrich Otto; David Pfister; Renate Pichler; Heinrich Recken; Oliver Rick; Yvonne Rudolph; Christian Ruf; Joachim Schirren; Hans Schmelz; Heinz Schmidberger; Mark Schrader; Stefan Schweyer; Stefanie Seeling; Rainer Souchon; Christian Winter; Christian Wittekind; Friedemann Zengerling; D H Zermann; Roger Zillmann; Peter Albers Journal: Urol Int Date: 2021-01-22 Impact factor: 2.089
Authors: Mette S Mortensen; Mikkel Bandak; Maria G G Kier; Jakob Lauritsen; Mads Agerbaek; Niels V Holm; Hans von der Maase; Gedske Daugaard Journal: Cancer Date: 2016-11-28 Impact factor: 6.860
Authors: T Tandstad; O Ståhl; U Håkansson; O Dahl; H S Haugnes; O H Klepp; C W Langberg; A Laurell; J Oldenburg; A Solberg; K Söderström; E Cavallin-Ståhl; U Stierner; R Wahlquist; N Wall; G Cohn-Cedermark Journal: Ann Oncol Date: 2014-08-11 Impact factor: 32.976
Authors: Timothy Gilligan; Daniel W Lin; Rahul Aggarwal; David Chism; Nicholas Cost; Ithaar H Derweesh; Hamid Emamekhoo; Darren R Feldman; Daniel M Geynisman; Steven L Hancock; Chad LaGrange; Ellis G Levine; Thomas Longo; Will Lowrance; Bradley McGregor; Paul Monk; Joel Picus; Phillip Pierorazio; Soroush Rais-Bahrami; Philip Saylor; Kanishka Sircar; David C Smith; Katherine Tzou; Daniel Vaena; David Vaughn; Kosj Yamoah; Jonathan Yamzon; Alyse Johnson-Chilla; Jennifer Keller; Lenora A Pluchino Journal: J Natl Compr Canc Netw Date: 2019-12 Impact factor: 11.908
Authors: Phillip Martin Pierorazio; Peter Albers; Peter C Black; Torgrim Tandstad; Axel Heidenreich; Nicola Nicolai; Craig Nichols Journal: Eur Urol Date: 2018-01-12 Impact factor: 20.096