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.
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.
This is the first report of trametinib for a metastatic GCT with an NF1 mutation, suggesting a possible but limited treatment effect.
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.
IJU case reports. 2026 Jul 09*** epublish ***
Keita Goto, Toshiki Kijima, Yusuke Sato, Kousuke Watanabe, Hidenori Kage, Katsutoshi Oda, Tatsunori Shimoi, Kazuyuki Ishida, Haruki Kume, Takao Kamai
Department of Urology Dokkyo Medical University Mibu Japan., Department of Urology, Graduate School of Medicine The University of Tokyo Tokyo Japan., Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine The University of Tokyo Tokyo Japan., Department of Respiratory Medicine, Graduate School of Medicine The University of Tokyo Tokyo Japan., Division of Integrative Genomics, Graduate School of Medicine The University of Tokyo Tokyo Japan., Department of Medical Oncology National Cancer Center Hospital Tokyo Japan., Department of Diagnostic Pathology Dokkyo Medical University Mibu Japan.