Barcelona, Spain (UroToday.com) 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. This initial model relied on 5,202 cases treated between 1975 and 1990. However, whether this classification system is still relevant has not been elucidated.
At the ESMO 2019 annual congress, Dr. Silke Gillessen presented results of a collaborative effort to update and revalidate the IGCCCG NSGCT risk groups. The first goal of this study was to validate the original IGCCCG criteria and update survival rates in a modern cohort of patients with first-line treatment. The second goal was to identify new prognostic factors that may explain the heterogeneity of outcomes in the original IGCCC risk groups.
An international consortium (30 centers/groups) contributed data on 9,530 advanced NSGCT patients treated with cisplatin/etoposide based first-line chemotherapy treated between 1990 and 2013 in prospective cohorts or clinical trials. Gonadal and extragonal primaries were allowed. Updated 5-year progression-free (PFS) and overall survival (OS) rates were calculated. A subset of 4,874 patients with complete information on components of IGCCCG, age, and lung metastases were split into training (n=3536) and validation sets (n=1338).
Prognostic factors for PFS were identified in the training set (alpha=0.05) by Cox model, including (transformed) continuous factors and interactions.
Compared to the 1997 IGCCCG figures, the contemporary 5-year PFS was unchanged for good and intermediate-risk patients but significantly improved for poor-risk patients (41% to 54%). The 5-year OS was substantially better for all risk groups:
The subgroup with complete data was unbiased. Besides traditional IGCCCG components, the group found older age and lung metastases as negative determinants of PFS. A nomogram including AFP, HCG (both continuous), LDH >2.5x normal, mediastinal primary, non-pulmonary visceral metastases, age (linear) and lung metastases, with several interactions, was built:
The c-index for this model was 0.745 in the training set compared to 0.701 for the 1997 IGCCCG model. Dr. Gillessen and her group have also developed a new NSGCT online calculator, which will be available soon.
Dr. Gillessen concluded her presentation with several take-home messages:
- PFS improved for poor-risk patients, while OS improved in all IGCCCG risk groups
- A new prognostic model including older age (linear association) and the 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
- A new IGCCCG Update calculator has been proposed, which has good prediction accuracy and discrimination
Co-Authors: S. Gillessen 1, L. Collette 2, G. Daugaard 3, R. De Wit 4, A. Tryakin 5, C. Albany 6, O. Stahl 7, K. Fizazi 8, J. Gietema 9, U. De Giorgi 10, A. Hansen 11, D. Feldman 12, F. Cafferty 13, T. Tandstad 14, X. Garcia Del Muro 15, R. Huddart 16, C. Sweeney 17, D. Heng 18, N. Sauve 2, J. Beyer 19
1. Medical Oncology-Hematology Department at the Kantonsspital St. Gallen, St Gallen, Switzerland
2. EORTC – European Organisation for Research and Treatment of Cancer, Brussels, BE
3. Rigshospitalet, Copenhagen University Hospital, Copenhagen, DK
4. Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, NL
5. N. N. Blokhin Russian Cancer Research Center, Moscow, RU
6. Indiana University, Indianapolis, US
7. Skane University Hospital, Lund, SE
8. Institut Gustave Roussy, Villejuif, FR
9. University Hospital Groningen (UMCG), Groningen, NL
10. Istituto Tumori della Romagna I.R.S.T., Meldola, IT
11. Princess Margaret Cancer Center, Toronto, CA
12. Memorial Sloan Kettering Cancer Centre, New York, US
13. Medical Research Council, London, UK
14. St Olav's University Hospital, Trondheim, NO
15. ICO - Institut Catala d'Oncologia Hospital Duran i Reynals, Hospitalet de Llobregat, ES
16. Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
17. Dana Farber Cancer Institute, Boston, US
18. University of Calgary, Calgary, CA
19. University Hospital Zürich, Zurich, CH
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept - 1 Oct 2019 in Barcelona, Spain