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 ( ≥ 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 ( ≤ 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 > 50% lung involvement, dyspnoea, and haemoptysis, but not choriocarcinoma histology or bleomycin use. Mostly, ED (51%) was associated with liver metastases, massive lung involvement, β-hCG > 50,000 mIU/mL, ECOG 2-3, elevated neutrophil/lymphocyte ratio, and need for intensive care (all P < 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.
British journal of cancer. 2026 Jun 02 [Epub ahead of print]
Michal Mego, Edgar Israelyan, Robert J Hamilton, Axel Heidenreich, Umberto Basso, Patrizia Giannatempo, Tomas Buchler, Klaus-Peter Dieckmann, Robert Huddart, Bruno Vincenzi, Kwonoh Park, Jorge Aparicio, Alexei Tryakin, Ali Amiri, Pavlina Malcharkova, Melanie Claps, Marija Miletic, Lucia Chaloupkova, Markus Angerer, Philippe E Spiess, Ugo De Giorgi, Global Society for Rare GU Tumors
Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia. ., N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia., Princess Margaret Cancer Centre, Toronto, ON, Canada., Department of Urology, Uro-Oncology, Robot Assisted and Specialized Urologic Surgery, University Hospital Cologne, Köln, Germany., Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy., Genitourinary Oncology Unit, Department of Medical Oncology and Ematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Motol University Hospital, Prague, Czech Republic., Asklepios Klinik Altona, Dept, Urology, Hamburg, Germany., The Royal Marsden NHS Foundation Trust, London, UK., University Campus Bio-Medico, Rome, Italy., Hanyang University Seoul Hospital, Hanyang University College of Medicine, Seoul, Korea., University and Polytechnic Hospital La Fe, Valencia, Spain., Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia., Department of GU Oncology, Moffitt Cancer Center, Tampa, USA., Department of Experimetal Medicine, University of Salento, Fazzi Hospital, Lecce, Italy.