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The IGCCCG Update Model Allows Improved and More Granular Individual Prognostic Assessment in Metastatic Non-Seminomatous Germ Cell Tumours

A new web-based calculator based on the results of the International Germ Cell Cancer Collaborative Group (IGCCCG) Update analysis allows improved and more granular individual prognostic assessment in patients with metastatic non-seminomatous germ cell tumours (NSGCT) and can help to shape strategies for future clinical trials.

Dr Silke Gillessen of the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland and the IGCCCG Update Consortium investigators wrote on 6 April 2021 in the Journal of Clinical Oncology that the original IGCCCG classification retains its relevance as a reference for treatment decisions in daily practice. The new IGCCCG Update model includes age and lung metastases as additional adverse prognostic factors and uses a single cut-off of lactate dehydrogenase (LDH) at 2.5 upper limit of normal (ULN).

The IGCCCG Update Consortium collected data on metastatic NSGCT with goals to validate the original IGCCCG criteria and update survival probabilities in a modern cohort, as well as to explore additional prognostic factors that may add granularity to the original IGCCCG prognostic groups and explain some of the heterogeneities found within the groups of the original IGCCCG classification.

The authors wrote in the background that according to the original IGCCCG classification, metastatic NSGCT are split into good, intermediate, and poor prognostic categories based on levels of alpha-fetoprotein, human chorionic gonadotropin, and LDH, as well as the presence of non-pulmonary visceral metastases. In addition, all primary mediastinal NSGCT are classified as poor, irrespective of other factors. However, patients included in the original IGCCCG analysis were treated between 1975 and 1990, and not all had received cisplatin or etoposide, which is the current treatment backbone for metastatic NSGCT.

The IGCCCG Update Consortium collected data on 9,728 men with metastatic NSGCT treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 in 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included.

Primary endpoints were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set.

Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis (89% versus 90%), but the 5-year OS increased from 92% to 96%.

In patients with intermediate prognosis, PFS remained similar (75% versus 78%) and the OS increased from 80% to 89%.

In patients with poor prognosis, the PFS increased from 41% to 54% and the OS increased from 48% to 67%.

The IGCCCG Update Consortium reported that a more granular prognostic model was developed and independently validated. This model identified a new cut-off of LDH at a 2.5x ULN, increasing age and presence of lung metastases as additional adverse prognostic factors.

The authors wrote that the OS of patients treated with first-line chemotherapy for metastatic NSGCT has improved over the last 20 years. However, despite these improvements, more than 30% of patients with poor prognostic features may still die of their disease. 

They concluded that the IGCCCG Update model improves individual prognostication in metastatic NSGCT. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

This work was supported by grants and donations from the EORTC Genito-urinary Cancer Group, the Swiss Cancer Foundation and Movember.

Reference

Gillessen S, Sauvé N, Collette L, et al. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium. Journal of Clinical Oncology; Published online 6 April 2021. DOI: 10.1200/JCO.20.03296

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