In an analysis of a modern cohort of patients with metastatic seminoma reported in the Journal of Clinical Oncology, Beyer et al, members of the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium, found that progression-free and overall survival have improved compared with an earlier cohort and that adding elevated lactate dehydrogenase as an adverse prognostic factor may improve prognostic groupings in IGCCCG classification.
As stated by the investigators, “The classification of the 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…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…We re-evaluated this classification in a database from a large international consortium.”
Progression-free survival and overall survival in [patients with] 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 [times] upper limit of normal as an additional adverse prognostic factor.— Beyer et al
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Study Details
The study included data on 2,451 men (2,329 good prognosis, 122 intermediate prognosis) with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 collected from 30 institutions or collaborative groups in Australia, Europe, and North America. The primary outcome measures were progression-free and overall survival calculated from day 1 of treatment.
Candidate variables assessed for prognostic impact included pretreatment human chorionic gonadotropin as a continuous variable, pretreatment LDH levels according to upper limit of normal (ULN), site of primary disease, age, and presence of lung metastases. The prognostic model analysis set consisted of 1,176 good-prognosis patients with data on all candidate variables and progression-free survival data; no analysis was performed in intermediate-prognosis patients due to the small number of patients with such data (n = 62).
Findings were evaluated in an independent validation cohort of 764 patients, consisting of additional patients from the institutions contributing to the analysis set and patients from six new centers in Australia, Croatia, Spain, Switzerland, and the United Kingdom; patients treated between 2013 and March 2016 were permitted in the validation cohort, since outcome data were sufficiently mature to reach 3 years of expected follow-up.
Key Findings
Compared with the initial IGCCCG cohort, 5-year progression-free survival improved from 82% to 89% and 5-year overall survival improved from 86% to 95% in good-prognosis patients in the modern cohort and from 67% to 79% and from 72% to 88%, respectively, in intermediate-prognosis patients in the modern cohort.
Among candidate prognostic variables, LDH standardized by ULN was the single most significant prognostic factor for progression-free survival in good-prognosis patients. Good-prognosis patients with LDH > 2.5 times ULN (n = 260) had a 3-year progression-free survival of 80% and 3-year overall survival of 92% vs rates of 92% and 97%, respectively, among patients with lower LDH (n = 916).
In the validation cohort, good-prognosis patients with LDH > 2.5 times ULN (n = 114) had 3-year progression-free survival of 75% vs 96% among those with lower LDH (n = 600). The difference in 3-year overall survival appeared to be consistent (96% vs 99%), but comparison was hampered by the small number of deaths (8 in 600 patients and 4 in 14 patients).
The investigators concluded, “Progression-free survival and overall survival in [patients with] 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 [times] upper limit of normal as an additional adverse prognostic factor.”
Jörg Beyer, MD, of the Department of Medical Oncology, Inselspital, University Hospital Bern, 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, Swiss Cancer Foundation, and Movember. For full disclosures of the study authors, visit ascopubs.org.
