In a study reported in the Journal of Clinical Oncology, Silke Gillessen, MD, and colleagues in the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium analyzed outcomes in a more contemporary cohort of men with metastatic nonseminomatous germ cell tumors. They also developed a new prognostic model (IGCCCG Update model) that adds three variables to the original IGCCCG model.
As stated by the investigators, “The classification of the IGCCCG plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.”
Silke Gillessen, MD
Study Details
The updated dataset included data from 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 collected from 30 institutions or collaborative groups in Europe, North America, and Australia. The primary outcome measures were progression-free and overall survival. Outcomes in this contemporary cohort were compared with those in the original IGCCCG cohort, which included patients treated between 1975 and 1990.
A novel prognostic model was developed for progression-free survival using a training set of 3,543 patients from the contemporary cohort with complete data on potentially relevant variables. The model was tested in an independent validation set of 1,360 additional patients. Accuracy of the model was assessed using the integrated Brier score (IBS)—a measure of prediction error ranging from 0 (perfect accuracy) to 1 (totally inaccurate)—and the receiver operating characteristic area under the curve (AUC).
Key Findings
For the original IGCCCG cohort vs the contemporary cohort:
- 5-year progression-free survival was 89% vs 90% and overall survival was 92% vs 96% among men in the IGCCCG good-prognosis group
- Corresponding figures were 75% vs 78% and 80% vs 89% among men with an intermediate prognosis
- Corresponding figures were 41% vs 54% and 48% vs 67% among men in the poor-prognosis category.
Development of a new prognostic model for progression-free survival in the training set identified three variables in addition to those included in the original IGCCCG prognostic model that were significant predictors of poorer outcome:
- 10-year increase in age (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.15–1.36)
- Lactate dehydrogenase level > 2.5 upper limit of normal (HR = 1.46, 95% CI = 1.18–1.81, in absence of nonpulmonary visceral metastases; HR = 1.01, 95% CI = 0.74–1.36, in presence of nonpulmonary visceral metastases)
- Presence of lung metastases (HR = 1.62, 95% CI = 1.36–1.92).
As in the original model, nonpulmonary visceral metastases (HR = 6.61, 95% CI = 4.62–9.46) and mediastinal primary tumor (HR = 2.68, 95% CI = 2.04–3.53) were the strongest prognostic factors.
In the training set, the IGCCCG Update model had an IBS of 0.10 and a time-dependent 3-year AUC of 0.76 (95% CI = 0.73–0.78). In the validation set, the model had an IBS of 0.11 and a 3-year AUC of 0.74 (95% CI = 0.70–0.77).
An online calculator using the IGCCCG Update model is available at: eortc.org/IGCCCG-Update.
The investigators concluded, “The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.”
Silke Gillessen, MD, of the Oncology Institute of Southern Switzerland (IOSI), Ospedale San Giovanni, Bellinzona, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants and donations from the EORTC Genito-urinary Cancer Group, the Swiss Cancer Foundation, and Movember. For full disclosures of the study authors, visit ascopubs.org.
