The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3)

Abstract

Purpose The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. Methods Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). Results The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. Conclusions LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis

“…The prognostic value of S-LDH was accepted worldwide after the international large collaborative study in 1997 [ 26 ]. Recently, the Global Germ Cell Tumor Collaboration documented the prognostic value of S-LDH for patients with advanced SE (hazard ratio 2.9, p = 0.003) and patients with NS with intermediate prognosis (hazard ratio 2.6, p < 0.001) [ 170 ].…”

“…For patients with high-risk metastatic TGCT who fail on standard BEP chemotherapy, the decay of two serum tumor markers, S-AFP and S-hCG, pointed to the cisplatin-resistance as early as after the first course of BEP [ 29 , 184 ]. Overall, the prognostic value of the three serum tumor markers is documented in prospective follow-up studies of more than 10,000 patients with TGCT [ 26 , 170 , 182 , 183 ].…”

Improving outcomes in germ cell cancers using miRNA

“…[25][26][27] Ultimately, AFP, hCG, and LDH are only elevated in 26-34%, 38-47%, and 33-44% of men at diagnosis with any TGCT, respectively, 28 making their role in surveillance of men without elevation fraught. In seminoma, the value of serum tumor biomarkers is particularly low, with elevation of AFP, hCG, and LDH seen in <3%, 26,[28][29][30] 18-31%, 26,31 and ~30% 32,33 at diagnosis, respectively, and similarly low rates are also seen at the time of relapse are also seen. 21 In fact, in the event of a significant elevation of serum tumor biomarkers in tumors otherwise thought to represent pure seminoma histologically, the diagnosis is revised from pure seminoma to NSGCT.…”