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Risk factors and causes of early death in germ cell tumors: a Global Society for Rare GU tumors study.

Source: PubMed, NCBI / U.S. National Library of Medicine

British journal of cancerMego Michal, Israelyan Edgar, Hamilton Robert J, et al.Published 6/2/2026Last synced 6/3/2026Status: syncedPMID: 42231028DOI: 10.1038/s41416-026-03484-0

Germ cell tumors (GCTs) are highly curable, yet a subset of patients with metastatic disease experience early death (ED) soon after starting first-line chemotherapy. These patients are underrepresented in trials, and risk factors remain unclear. We performed a retrospective multicenter cohort study including adults (&#x2009;&#x2265;&#x2009;18 years) with metastatic GCT who died within 3 months of completing their last cycle of first-line chemotherapy. Primary outcomes were cause and timing of death; secondary endpoints included clinical predictors of acute respiratory failure (ARF) and very early death (&#x2009;&#x2264;&#x2009;30 days). Among 102 patients (1.7% of treated cases), 69.6% had non-seminoma, 83.3% testicular primaries, and 67.6% poor-risk disease. Median time to death was 28 days (range, 2-179). Leading causes were ARF (34.1%), disease progression (16.7%), septic shock (15.7%), hemorrhage (12.7%), and cardiovascular events (4.0%). ARF correlated with >&#x2009;50% lung involvement, dyspnoea, and haemoptysis, but not choriocarcinoma histology or bleomycin use. Mostly, ED (51%) was associated with liver metastases, massive lung involvement, &#x3b2;-hCG >&#x2009;50,000&#x2009;mIU/mL, ECOG 2-3, elevated neutrophil/lymphocyte ratio, and need for intensive care (all P&#x2009;<&#x2009;0.05). Early death in metastatic GCT, though rare, remains a critical clinical issue. Early identification, adapted induction regimens, and optimized supportive care may help prevent avoidab

Abstract

Germ cell tumors (GCTs) are highly curable, yet a subset of patients with metastatic disease experience early death (ED) soon after starting first-line chemotherapy. These patients are underrepresented in trials, and risk factors remain unclear. We performed a retrospective multicenter cohort study including adults (&#x2009;&#x2265;&#x2009;18 years) with metastatic GCT who died within 3 months of completing their last cycle of first-line chemotherapy. Primary outcomes were cause and timing of death; secondary endpoints included clinical predictors of acute respiratory failure (ARF) and very early death (&#x2009;&#x2264;&#x2009;30 days). Among 102 patients (1.7% of treated cases), 69.6% had non-seminoma, 83.3% testicular primaries, and 67.6% poor-risk disease. Median time to death was 28 days (range, 2-179). Leading causes were ARF (34.1%), disease progression (16.7%), septic shock (15.7%), hemorrhage (12.7%), and cardiovascular events (4.0%). ARF correlated with >&#x2009;50% lung involvement, dyspnoea, and haemoptysis, but not choriocarcinoma histology or bleomycin use. Mostly, ED (51%) was associated with liver metastases, massive lung involvement, &#x3b2;-hCG >&#x2009;50,000&#x2009;mIU/mL, ECOG 2-3, elevated neutrophil/lymphocyte ratio, and need for intensive care (all P&#x2009;<&#x2009;0.05). Early death in metastatic GCT, though rare, remains a critical clinical issue. Early identification, adapted induction regimens, and optimized supportive care may help prevent avoidable mortality.

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