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Proffered Paper 2 – Genitourinary tumours, non-prostate

2303 - Redefining the IGCCCG Classification in advanced Non-Seminoma

Date

28 Sep 2019

Session

Proffered Paper 2 – Genitourinary tumours, non-prostate

Topics

Tumour Site

Malignant Germ-Cell Tumours of the Adult Male

Presenters

Silke Gillessen

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

S. Gillessen1, L. Collette2, G. Daugaard3, R. de Wit4, A. Tryakin5, C. Albany6, O. Stahl7, K. Fizazi8, J.A. Gietema9, U.F.F. De Giorgi10, A.R. Hansen11, D. Feldman12, F. Cafferty13, T. Tandstad14, X. Garcia del Muro15, R.A. Huddart16, C.J. Sweeney17, D.Y.C. Heng18, N. Sauve2, J. Beyer19

Author affiliations

  • 1 Department Of Oncology/hematology  , The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2 Statistics, EORTC - European Organisation for Research and Treatment of Cancer, 1200 - Brussels/BE
  • 3 Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 4 Oncology, Erasmus MC Daniel den Hoed Cancer Center, 3075EA - Rotterdam/NL
  • 5 Oncology, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 6 Oncology, Indiana University, IN 46202 - Indianapolis/US
  • 7 Oncology, Skane University Hospital, SE-221 41 - Lund/SE
  • 8 Cancer Medicine, Gustave Roussy, 94805 - Villejuif/FR
  • 9 Medical Oncology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 10 Medical Oncology Department, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 11 Medical Oncology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 12 Medicine, Memorial Sloan Kettering Cancer Centre, NY 10065 - New York/US
  • 13 Institute Of Clinical Trials & Methodology, Medical Research Council, NW1 2DA - London/GB
  • 14 Oncology, St Olav's University Hospital, 7045 - Trondheim/NO
  • 15 Medical Oncology, ICO - Institut Catala d'Oncologia Hospital Duran i Reynals, 08907 - Hospitalet de Llobregat/ES
  • 16 Radiotherapy And Imaging, Royal Marsden Hospital Institute of Cancer Research, SM2 5NG - Sutton/GB
  • 17 Medical Oncology, Dana Farber Cancer Institute, 02115 - Boston/US
  • 18 Oncology, University of Calgary, Calgary/CA
  • 19 Medical Oncology, University Hospital Zürich, 8091 - Zurich/CH

Resources

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Abstract 2303

Background

The International Germ Cell Cancer Collaborative Group (IGCCCG) has been the reference classification for assessing prognosis in men with advanced non-seminomatous germ-cell tumors (NSGCT) for more than 20 years and it relied on 5202 cases treated between 1975 and 1990.

Methods

An international consortium (30 centers/groups) contributed data on 9530 advanced NSGCT patients treated with cisplatin/etoposide based first line chemotherapy between 1990 and 2013 in prospective cohorts or clinical trials. Updated 5-year progression-free (PFS) and overall survival (OS) rates were calculated. A subset of 4874 patients with complete information on components of IGCCCG, age and lung metastases were split into training (3536) and validation sets (1338). Prognostic factors for PFS were identified in the training set (alpha=0.05) by Cox model, including (transformed) continuous factors and interactions.

Results

Compared to the 1997 IGCCCG figures, the contemporary 5-year PFS was unchanged for good and intermediate, but significantly improved for poor risk patients; whereas 5-year OS was substantially better for all risk groups (Table). The subgroup with complete data was unbiased. Besides traditional IGCCCG components, we identified older age and lung metastases as negative determinants of PFS. A nomogram including AFP, HCG (both continuous), LDH>2.5xnormal, mediastinal primary, non-pulmonary visceral metastases, age (linear) and lung metastases, with several interactions was built. Its c-index was 0.745 in the training set compared to 0.701 for the 1997 IGCCCG.Table:

903O

5-year PFS IGCCCG 19975-year PFS contemporary5-year OS IGCCCG 19975-year OS contemporary
Good89 (87 – 91%)90 (89 - 91%)91 (89 - 93%)96 (95 - 97%)
Intermediate75 (71 – 79%)78 (76 - 80%)79 (75 - 83%)89 (88 - 91%)
Poor41 (35 – 47%)54 (52 - 56%)48 (42 - 54%)67 (65 - 69%)

Conclusions

In this modern series, PFS improved for poor risk patients, while OS improved in all IGCCCG risk groups. A new prognostic model including older age and presence of lung metastases as additional negative factors is proposed. Independent validation and comparison to the IGCCCG 1997 are being conducted and will tell if the model can identify patient subgroups who may require intensified treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The International Germ Cell Cancer Collaborative Group (IGCCCG).

Funding

Swiss Cancer Foundation.

Disclosure

S. Gillessen: Advisory / Consultancy: AAA International, Active Biotech, Amgen, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch, Clovis, CureVac, Dendreon, ESSA Pharmaceuticals, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxiVAX SA, Millennium, Nectar, Novartis, Orion, Pfizer,; Licensing / Royalties: Co-inventor on patent application (WO 2009138392 A1) for a method for biomarker discover (granted in China, Europe, Japan and the US). R. de Wit: Honoraria (self): Merck, Sanofi, Bayer, Janssen, Roche and Clovis. R.A. Huddart: Honoraria (self): Janssen; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (self): CRUK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar. All other authors have declared no conflicts of interest.

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