Abstract
PURPOSEThe classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.MATERIALS AND METHODSData on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.RESULTSCompared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.CONCLUSIONPFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
Highlights
About one third of patients with seminoma present with metastatic disease
progression-free survival (PFS) and overall survival (OS) in metastatic seminoma significantly improved in our modern series compared with the original data
According to the original International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, metastatic seminomas are split into good or intermediate prognosis categories based on the presence or absence of liver, bone, or brain metastases.[1]
Summary
About one third of patients with seminoma present with metastatic disease. The relevance of the original IGCCCG classification has been challenged. According to the original IGCCCG classification, metastatic seminomas are split into good or intermediate prognosis categories based on the presence or absence of liver, bone, or brain metastases.[1] as data from only 660 patients with seminoma had been analyzed, the ability to assess the impact of other relevant variables such as age, lactate dehydrogenase (LDH), elevated human chorionic gonadotropin (HCG) levels, or the presence of pulmonary metastases was limited. Patients with seminoma included in the original IGCCCG analysis were treated between 1975 and 1990 and many had not received cisplatin or etoposide, which would be the treatment backbone for metastatic seminoma today.[2,3]
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