Redefining the IGCCCG classification in advanced non-seminoma

Abstract

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

Empty Cell	5-year PFS IGCCCG 1997	5-year PFS contemporary	5-year OS IGCCCG 1997	5-year OS contemporary
Good	89 (87 – 91%)	90 (89 - 91%)	91 (89 - 93%)	96 (95 - 97%)
Intermediate	75 (71 – 79%)	78 (76 - 80%)	79 (75 - 83%)	89 (88 - 91%)
Poor	41 (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.

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.