Metastatic Testicular Germ Cell Tumor in a Patient With Neurofibromatosis Type 1: Treatment With Trametinib Based on NF1 Gene Mutation

Keita Goto; Toshiki Kijima; Yusuke Sato; Kousuke Watanabe; Hidenori Kage; Katsutoshi Oda; Tatsunori Shimoi; Kazuyuki Ishida; Haruki Kume; Takao Kamai

doi:10.1002/iju5.70223

Metastatic Testicular Germ Cell Tumor in a Patient With Neurofibromatosis Type 1: Treatment With Trametinib Based on NF1 Gene Mutation

IJU Case Rep. 2026 Jul 9;9(4):e70223. doi: 10.1002/iju5.70223. eCollection 2026 Jul.

Authors

Keita Goto¹, Toshiki Kijima¹, Yusuke Sato^{2

3}, Kousuke Watanabe⁴, Hidenori Kage⁵, Katsutoshi Oda⁶, Tatsunori Shimoi⁷, Kazuyuki Ishida⁸, Haruki Kume², Takao Kamai¹

Affiliations

¹ Department of Urology Dokkyo Medical University Mibu Japan.
² Department of Urology, Graduate School of Medicine The University of Tokyo Tokyo Japan.
³ Department of Urology Tokyo Metropolitan Tama Medical Center Tokyo Japan.
⁴ Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine The University of Tokyo Tokyo Japan.
⁵ Department of Respiratory Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan.
⁶ Division of Integrative Genomics, Graduate School of Medicine The University of Tokyo Tokyo Japan.
⁷ Department of Medical Oncology National Cancer Center Hospital Tokyo Japan.
⁸ Department of Diagnostic Pathology Dokkyo Medical University Mibu Japan.

Abstract

Introduction: Neurofibromatosis type 1 (NF1) is a genetic disorder that increases the risk of various tumors. However, its association with testicular germ cell tumors (GCTs) is rare. We report a case of metastatic GCT in an NF1 patient treated with precision medicine.

Case presentation: A 40-year-old male with NF1 presented with a left testicular non-seminomatous GCT and lung metastases. The tumor showed progressive disease after chemotherapy (VIP, TGP) and surgical removal of metastases. Comprehensive genomic profiling (CGP) test found a pathogenic NF1 frameshift mutation (p.Q514fs*43). Based on this finding, the patient received the MEK inhibitor trametinib under patient-proposed healthcare services (BELIEVE Trial). Treatment resulted in normalization of serum alpha-fetoprotein (AFP) for 6 months before the tumor eventually progressed. The patient died at 39 months after diagnosis.

Conclusion: This is the first report of trametinib for a metastatic GCT with an NF1 mutation, suggesting a possible but limited treatment effect.

Trial registration: The prospective trial of patient-proposed healthcare services with multiple targeted agents based on the results of gene profiling by multigene panel test (BELIEVE), NCCH1901/jRCTs031190104.

Keywords: MEK inhibitor; neurofibromatosis type 1; precision medicine; testicular germ cell tumor; trametinib.