Multicenter Study

. 2021 May 10;39(14):1553-1562.

doi: 10.1200/JCO.20.03292. Epub 2021 Mar 17.

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

Jörg Beyer¹, Laurence Collette², Nicolas Sauvé², Gedske Daugaard³, Darren R Feldman^{4

5}, Torgrim Tandstad⁶, Alexey Tryakin^{7

8}, Olof Stahl⁹, Enrique Gonzalez-Billalabeitia^{10

11}, Ugo De Giorgi¹², Stéphane Culine¹³, Ronald de Wit¹⁴, Aaron R Hansen¹⁵, Marko Bebek¹⁶, Angelika Terbuch¹⁷, Costantine Albany¹⁸, Marcus Hentrich¹⁹, Jourik A Gietema²⁰, Helene Negaard²¹, Robert A Huddart²², Anja Lorch^{23

24}, Fay H Cafferty²⁵, Daniel Y C Heng²⁶, Christopher J Sweeney²⁷, Eric Winquist²⁸, Michal Chovanec²⁹, Christian Fankhauser³⁰, Daniel Stark³¹, Peter Grimison³², Andrea Necchi³³, Ben Tran³⁴, Axel Heidenreich³⁵, Jonathan Shamash³⁶, Cora N Sternberg³⁷, David J Vaughn³⁸, Ignacio Duran³⁹, Carsten Bokemeyer⁴⁰, Anna Patrikidou⁴¹, Richard Cathomas⁴², Samson Assele², Silke Gillessen^{43

44

45}; International Germ Cell Cancer Classification Update Consortium

Affiliations

¹ Department of Medical Oncology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
² European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
³ Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁴ Memorial Sloan Kettering Cancer Center, New York, NY.
⁵ Weill Medical College of Cornell University, New York, NY.
⁶ The Cancer Clinic, St Olavs University Hospital and Department of Clinical and Molecular Medicine, The Norwegian University of Science and Technology, Trondheim, Norway.
⁷ N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
⁸ Research Institute of Oncology at Bashkir State Medical University, Ufa, Russian Federation.
⁹ Department of Oncology, Skåne University Hospital, Lund, Sweden.
¹⁰ Servicio de Oncologia Medica, Hospital Universitario 12 de Octubre, Madrid, Spain.
¹¹ Universidad Catolica San Antonio de Murcia, UCAM, Murcia, Spain.
¹² Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy and the Italian Germ Cell Cancer Group (IGG), Italy.
¹³ Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Faculté de Paris, Paris, France.
¹⁴ Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
¹⁵ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
¹⁶ Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia.
¹⁷ Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
¹⁸ Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.
¹⁹ Department of Hematology and Oncology, Red Cross Hospital, University of Munich, Munich, Germany.
²⁰ University Medical Center Groningen, Groningen, the Netherlands.
²¹ Department of Oncology, Oslo University Hospital, Oslo, Norway.
²² Institute of Cancer Research, Sutton, United Kingdom.
²³ Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
²⁴ Department of Urology, University Hospital Dusseldorf, Dusseldorf, Germany.
²⁵ Medical Research Council Clinical Trials Unit at University College London (UCL), London, United Kingdom.
²⁶ Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
²⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
²⁸ Division of Medical Oncology, Western University and London Health Sciences Centre, London, Ontario, Canada.
²⁹ 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.
³⁰ University of Zurich, Zurich, Switzerland.
³¹ Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom.
³² Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia.
³³ 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.
³⁴ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
³⁵ Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany.
³⁶ St Bartholomew's Hospital, London, United Kingdom.
³⁷ Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy. Current affiliation: Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY.
³⁸ University of Pennsylvania, Philadelphia, PA.
³⁹ Hospital Universitario Marques de Valdecilla and IDIVAL, Santander, Spain.
⁴⁰ Department of Oncology, Hematology and BMT with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴¹ Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Current affiliation: Sarah Cannon Research Institute and UCL Cancer Institute, London, United Kingdom.
⁴² Division of Oncology/Hematology, Cantonal Hospital Graubunden, Chur, Switzerland.
⁴³ Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
⁴⁴ Universita della Svizzera Italiana, Lugano, Switzerland.
⁴⁵ University of Manchester, Manchester, United Kingdom.

PMID: 33729863
PMCID: PMC8099394
DOI: 10.1200/JCO.20.03292

Multicenter Study

Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

Jörg Beyer et al. J Clin Oncol. 2021.

. 2021 May 10;39(14):1553-1562.

doi: 10.1200/JCO.20.03292. Epub 2021 Mar 17.

Authors

Affiliations

¹ Department of Medical Oncology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
² European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
³ Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
⁴ Memorial Sloan Kettering Cancer Center, New York, NY.
⁵ Weill Medical College of Cornell University, New York, NY.
⁶ The Cancer Clinic, St Olavs University Hospital and Department of Clinical and Molecular Medicine, The Norwegian University of Science and Technology, Trondheim, Norway.
⁷ N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.
⁸ Research Institute of Oncology at Bashkir State Medical University, Ufa, Russian Federation.
⁹ Department of Oncology, Skåne University Hospital, Lund, Sweden.
¹⁰ Servicio de Oncologia Medica, Hospital Universitario 12 de Octubre, Madrid, Spain.
¹¹ Universidad Catolica San Antonio de Murcia, UCAM, Murcia, Spain.
¹² Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy and the Italian Germ Cell Cancer Group (IGG), Italy.
¹³ Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Faculté de Paris, Paris, France.
¹⁴ Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
¹⁵ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
¹⁶ Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia.
¹⁷ Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
¹⁸ Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.
¹⁹ Department of Hematology and Oncology, Red Cross Hospital, University of Munich, Munich, Germany.
²⁰ University Medical Center Groningen, Groningen, the Netherlands.
²¹ Department of Oncology, Oslo University Hospital, Oslo, Norway.
²² Institute of Cancer Research, Sutton, United Kingdom.
²³ Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
²⁴ Department of Urology, University Hospital Dusseldorf, Dusseldorf, Germany.
²⁵ Medical Research Council Clinical Trials Unit at University College London (UCL), London, United Kingdom.
²⁶ Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
²⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
²⁸ Division of Medical Oncology, Western University and London Health Sciences Centre, London, Ontario, Canada.
²⁹ 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.
³⁰ University of Zurich, Zurich, Switzerland.
³¹ Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom.
³² Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, Australia.
³³ 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.
³⁴ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
³⁵ Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany.
³⁶ St Bartholomew's Hospital, London, United Kingdom.
³⁷ Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy. Current affiliation: Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY.
³⁸ University of Pennsylvania, Philadelphia, PA.
³⁹ Hospital Universitario Marques de Valdecilla and IDIVAL, Santander, Spain.
⁴⁰ Department of Oncology, Hematology and BMT with Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴¹ Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Current affiliation: Sarah Cannon Research Institute and UCL Cancer Institute, London, United Kingdom.
⁴² Division of Oncology/Hematology, Cantonal Hospital Graubunden, Chur, Switzerland.
⁴³ Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.
⁴⁴ Universita della Svizzera Italiana, Lugano, Switzerland.
⁴⁵ University of Manchester, Manchester, United Kingdom.

PMID: 33729863
PMCID: PMC8099394
DOI: 10.1200/JCO.20.03292

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

Jörg BeyerHonoraria: Roche, Janssen Oncology, AstraZeneca, Astellas Pharma, Bayer, Ipsen Gedske DaugaardConsulting or Advisory Role: Sanofi/Aventis, Astellas Pharma, Bayer, MSD Oncology, Bristol-Myers Squibb/PfizerTravel, Accommodations, Expenses: Astellas Pharma Darren R. FeldmanResearch Funding: Novartis, Seattle Genetics, Decibel Therapeutics, Astellas PharmaOther Relationship: UpToDate Alexey TryakinConsulting or Advisory Role: BioCad, Roche/Genentech, Bristol-Myers Squibb, Eisai, Merck Sharp & DohmeSpeakers' Bureau: Bayer Health, BioCad, Lilly, Merck Serono, Sanofi, Amgen, Bristol-Myers Squibb, Eisai, Merck Sharp & DohmeTravel, Accommodations, Expenses: Novartis, BioCad, Bayer, Veropharm, Sanofi Olof StahlHonoraria: Bayer Enrique Gonzalez-BillalabeitiaTravel, Accommodations, Expenses: Bristol-Myers Squibb, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi, Roche Ugo De GiorgiConsulting or Advisory Role: Pfizer, Janssen, Astellas Pharma, Sanofi, Bristol-Myers Squibb, Bayer, Ipsen, Merck, MSD, PharmaMar, NovartisResearch Funding: Sanofi, AstraZeneca, RocheTravel, Accommodations, Expenses: Bristol-Myers Squibb, Ipsen, Janssen, Pfizer, Roche Stephane CulineConsulting or Advisory Role: Bayer, Janssen, Astellas PharmaSpeakers' Bureau: Takeda, JanssenResearch Funding: Astellas PharmaTravel, Accommodations, Expenses: Ipsen, Janssen Ronald De WitHonoraria: Sanofi, Merck Sharp & DohmeConsulting or Advisory Role: Sanofi, Merck Sharp & Dohme, Janssen, Bayer, Astellas PharmaResearch Funding: Sanofi, BayerTravel, Accommodations, Expenses: Bayer Aaron HansenConsulting or Advisory Role: Merck, GlaxoSmithKline, Bristol-Myers Squibb, EisaiResearch Funding: Karyopharm Therapeutics, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Janssen, AstraZeneca/MedImmune, Astellas Pharma, Macrogenics Marko BebekHonoraria: Roche, Novartis, Janssen Oncology, Sanofi, Sandoz, Astellas PharmaResearch Funding: Roche, Astellas PharmaTravel, Accommodations, Expenses: Roche, Astellas Pharma, Sanofi, Janssen, Novartis Angelika TerbuchResearch Funding: Roche, AstraZeneca, MSD, Bristol-Myers Squibb Costantine AlbanyStock and Other Ownership Interests: AdvaxisHonoraria: Sanofi, AstraZeneca, Seattle GeneticsConsulting or Advisory Role: Seattle Genetics, AstraZeneca/MedImmuneSpeakers' Bureau: SanofiResearch Funding: Astex Pharmaceuticals, Merck, Bristol-Myers Squibb, Lilly, BayerTravel, Accommodations, Expenses: Sanofi Marcus HentrichConsulting or Advisory Role: Amgen, Janssen-Cilag, Sanofi, Hexal, Jazz Pharmaceuticals, TakedaSpeakers' Bureau: Amgen, Janssen-Cilag, Sanofi, Takeda, Bristol-Myers Squibb, Gilead SciencesTravel, Accommodations, Expenses: Celgene, Janssen-Cilag, Takeda Jourik A. GietemaResearch Funding: Roche/Genentech, Abbvie, Siemens Robert A. HuddartEmployment: Aspen Parkside HospitalLeadership: Cancer Clinic London limited liability partnershipHonoraria: Janssen OncologyConsulting or Advisory Role: Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Janssen Oncology, Nektar, BayerSpeakers' Bureau: Roche, MSDResearch Funding: Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, JanssenPatents, Royalties, Other Intellectual Property: Royalties for drug discovery from JanssenTravel, Accommodations, Expenses: Janssen Oncology, Roche/Genentech, MSD Oncology, Nektar Anja LorchHonoraria: MSD Oncology, Merck, MSDConsulting or Advisory Role: Bristol-Myers Squibb, Novartis, AstraZeneca, Roche, MSD Oncology, Janssen Oncology, Ipsen, Merck, PfizerTravel, Accommodations, Expenses: Ipsen, AstraZeneca Daniel Y. C. HengConsulting or Advisory Role: Pfizer, Novartis, Bristol-Myers Squibb, Janssen, Astellas Pharma, Ipsen, Eisai, MerckResearch Funding: Pfizer, Novartis, Exelixis, Bristol-Myers Squibb, Ipsen Christopher J. SweeneyStock and Other Ownership Interests: LeuchemixConsulting or Advisory Role: Sanofi, Janssen Biotech, Astellas Pharma, Bayer, Genentech/Roche, AstraZeneca, Pfizer, Amgen, Celgene, LillyResearch Funding: Janssen Biotech, Astellas Pharma, Sanofi, Bayer, Dendreon, PfizerPatents, Royalties, Other Intellectual Property: Leuchemix, Parthenolide, Dimethylaminoparthenolide. Exelixis: Abiraterone plus cabozantinib combination Eric WinquistHonoraria: Merck, Bayer, Eisai, Amgen, RocheResearch Funding: Roche/Genentech, Merck, Pfizer, Eisai, Ayala Pharmaceuticals Peter GrimisonResearch Funding: Tilray, Pfizer, MSD, Gilead Sciences, Boston Biomedical, Tigermed, Halozyme, Specialised Therapeutics, Medimmune, Pfizer, ASLAN Pharmaceuticals, Genentech, Eisai, Five Prime Therapeutics, QED Therapeutics, Janssen-Cilag Andrea NecchiEmployment: BayerStock and Other Ownership Interests: BayerHonoraria: Roche, Merck, AstraZeneca, Janssen, Foundation Medicine, Bristol-Myers SquibbConsulting or Advisory Role: Merck Sharp & Dohme, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, GlaxoSmithKline, FerringResearch Funding: Merck Sharp & Dohme, AstraZeneca, IpsenTravel, Accommodations, Expenses: Roche, Merck Sharp & Dohme, AstraZeneca, Janssen, Rainier TherapeuticsOther Relationship: Bayer Ben TranHonoraria: Astellas Pharma, Janssen-Cilag, Sanofi, Tolmar, Amgen, Bristol-Myers SquibbConsulting or Advisory Role: Amgen, Astellas Pharma, Bayer, Sanofi, Tolmar, Janssen-Cilag, Bristol-Myers Squibb, Ipsen, MSD Oncology, IQvia, Novartis, Pfizer/EMD Serono, AstraZeneca, Roche Molecular DiagnosticsResearch Funding: Astellas Pharma, Janssen-Cilag, Amgen, Pfizer, Genentech, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, IpsenTravel, Accommodations, Expenses: Amgen, Astellas Pharma Axel HeidenreichHonoraria: Amgen, Astellas Pharma, Bayer, Ferring, Ipsen, Janssen-Cilag, Sanofi, TakedaConsulting or Advisory Role: Astellas Pharma, Bayer, Janssen-Cilag, Clovis Oncology, BMS Global, AstraZeneca, MSD OncologySpeakers' Bureau: Amgen, Astellas Pharma, Bayer, Ipsen, Johnson & Johnson, Sanofi, Takeda, PfizerResearch Funding: Astellas Pharma, Bayer, Sanofi, Bristol-Myers Squibb Jonathan ShamashSpeakers' Bureau: Pfizer/EMD Serono Cora N. SternbergConsulting or Advisory Role: Bayer, MSD, Pfizer, Roche, Incyte, AstraZeneca, Merck, Medscape, UroToday, Astellas Pharma, Genzyme, Immunomedics, Foundation Medicine David J. VaughnResearch Funding: Merck Sharp & Dohme, Roche/Genentech, Astellas Pharma Ignacio DuranHonoraria: Bristol-Myers Squibb, Ipsen, Roche/Genentech, Janssen Oncology, MSD Oncology, Astellas Pharma, EUSA PharmaConsulting or Advisory Role: Roche/Genentech, MSD Oncology, Bayer, Bristol-Myers Squibb, Seattle Genetics, Pharmacyclics, Janssen Oncology, Novartis, ImmunomedicsResearch Funding: Roche/Genentech, AstraZeneca Spain, Janssen Oncology, Astellas PharmaTravel, Accommodations, Expenses: Roche/Genentech, AstraZeneca Spain, Ipsen Carsten BokemeyerHonoraria: Merck KGaA, Sanofi, Roche, Bayer, Bristol-Myers Squibb, AstraZeneca, Merck Sharp & DohmeConsulting or Advisory Role: Lilly/ImClone, Merck Serono, Sanofi, Bayer Schering Pharma, Merck Sharp & Dohme, GSO, AOK Health InsuranceResearch Funding: Abbvie, ADC Therapeutics, Agile Therapeutics, Alexion Pharmaceuticals, Amgen, Apellis Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, BerGenBio, Blueprint Medicines, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eisai, Gilead Sciences, Glycotope GmbH, GlaxoSmithKline, Incyte, iOMEDICO, Isofol Medical, Janssen-Cilag, Karyopharm Therapeutics, Lilly, Millennium, MSD, Nektar, Novartis, Rafael Pharmaceuticals, Roche, Springworks Therapeutics, Taiho PharmaceuticalTravel, Accommodations, Expenses: Merck Serono, Sanofi, Pfizer, Bristol-Myers Squibb Anna PatrikidouConsulting or Advisory Role: Basilea Richard CathomasHonoraria: Janssen-Cilag, Astellas Pharma, Bristol-Myers Squibb, Debiopharm GroupConsulting or Advisory Role: Astellas Pharma, Bristol-Myers Squibb, Pfizer, Roche, MSD Oncology, Janssen-Cilag, Bayer, Sanofi, IpsenTravel, Accommodations, Expenses: AstraZeneca Silke GillessenConsulting or Advisory Role: Astellas Pharma, Janssen, Bayer, Orion Pharma GmbH, Tolero Pharmaceuticals, MSD Oncology, Roche, Amgen, PfizerSpeakers' Bureau: Janssen-CilagPatents, Royalties, Other Intellectual Property: Method for biomarker (WO 3752009138392 A1)Travel, Accommodations, Expenses: ProteoMedixOther Relationship: ProteoMediX, Aranda PharmaNo other potential conflicts of interest were reported.

Figures

**FIG 1.**
CONSORT diagram. OS, overall survival; PFS, progression-free survival.

**FIG 2.**
Survival probabilities and 95% CI according to original IGCCCG prognostic groups for (A) PFS and (B) OS. IGCCCG, International Germ-Cell Cancer Collaborative Group; OS, overall survival; PFS, progression-free survival.

**FIG 3.**
(A) PFS and (B) OS probabilities and 95% CI in the analysis set and (C, D) in the validation set by original International Germ-Cell Cancer Collaborative Group prognostic group with subdivision of good risk by LDH level (≤ 2.5 ULN, > 2.5 ULN). LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; ULN, upper limit of normal.

**FIG 4.**
Survival probabilities and 95% CI of good prognosis patients according to LDH levels in the analysis set for (A) PFS and (B) OS, as well as in the (C, D) validation set, restricted to patients treated with three BEP or four EP. BEP, bleomycin, etoposide, cisplatin; EP, etoposide, cisplatin; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; ULN, upper limit of normal.

**FIG A1.**
Survival probabilities and 95% CIs for patients in or out of the analysis set for (A) PFS and (B) OS. OS, overall survival; PFS, progression-free survival.

**FIG A2.**
Variable importance of all candidate variables on PFS in the prognostic model analysis set. HCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; ULN, upper limit of normal.

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Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

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Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium

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