The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.
Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.
Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.
PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021 Mar 17 [Epub ahead of print]
Jörg Beyer, Laurence Collette, Nicolas Sauvé, Gedske Daugaard, Darren R Feldman, Torgrim Tandstad, Alexey Tryakin, Olof Stahl, Enrique Gonzalez-Billalabeitia, Ugo De Giorgi, Stéphane Culine, Ronald de Wit, Aaron R Hansen, Marko Bebek, Angelika Terbuch, Costantine Albany, Marcus Hentrich, Jourik A Gietema, Helene Negaard, Robert A Huddart, Anja Lorch, Fay H Cafferty, Daniel Y C Heng, Christopher J Sweeney, Eric Winquist, Michal Chovanec, Christian Fankhauser, Daniel Stark, Peter Grimison, Andrea Necchi, Ben Tran, Axel Heidenreich, Jonathan Shamash, Cora N Sternberg, David J Vaughn, Ignacio Duran, Carsten Bokemeyer, Anna Patrikidou, Richard Cathomas, Samson Assele, Silke Gillessen, International Germ Cell Cancer Classification Update Consortium
Department of Medical Oncology, Inselspital, University Hospital, University of Bern, Bern, Switzerland., European Organisation for Research and Treatment of Cancer, Brussels, Belgium., Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Memorial Sloan Kettering Cancer Center, New York, NY., The Cancer Clinic, St Olavs University Hospital and Department of Clinical and Molecular Medicine, The Norwegian University of Science and Technology, Trondheim, Norway., N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation., Department of Oncology, Skåne University Hospital, Lund, Sweden., Servicio de Oncologia Medica, Hospital Universitario 12 de Octubre, Madrid, Spain., Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy and the Italian Germ Cell Cancer Group (IGG), Italy., Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Faculté de Paris, Paris, France., Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia., Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN., Department of Hematology and Oncology, Red Cross Hospital, University of Munich, Munich, Germany., University Medical Center Groningen, Groningen, The Netherlands., Department of Oncology, Oslo University Hospital, Oslo, Norway., Institute of Cancer Research, Sutton, United Kingdom., Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland., Medical Research Council Clinical Trials Unit at University College London (UCL), London, United Kingdom., Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Division of Medical Oncology, Western University and London Health Sciences Centre, London, Ontario, Canada., 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia., University of Zurich, Zurich, Switzerland., Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Current affiliation: Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany., St Bartholomew's Hospital, London, United Kingdom., Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy. Current affiliation: Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY., University of Pennsylvania, Philadelphia, PA., Hospital Universitario Marques de Valdecilla and IDIVAL, Santander, Spain., Department of Oncology, Hematology and BMT with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Current affiliation: Sarah Cannon Research Institute and UCL Cancer Institute, London, United Kingdom., Division of Oncology/Hematology, Cantonal Hospital Graubunden, Chur, Switzerland., Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.