Volume 23, Number 4Case ReviewExceptional Response to Radiation Therapy to the Primary Tumor in a Patient With de Novo Metastatic Prostate Cancer With High Tumor Mutation BurdenBenjamin MercierAndrew TamDaniela V. CastroSalvador Jaime-CasasAbhishek TripathiYun Rose LiRegina Barragan-CarrilloWe present the case of a patient diagnosed with de novo, low-volume metastatic prostate cancer who received first-line treatment with androgen-deprivation therapy in combination with darolutamide. The patient presented with symptoms derived from local growth from the primary tumor and received pelvic radiation therapy to the primary tumor and pelvic nodes. He experienced complete tumor regression, with high serum prostate-specific antigen declining to nondetectable levels. Next-generation genomic analysis indicated high tumor mutation burden and high microsatellite status instability. Here, we contextualize this patient’s case regarding the importance of precision genomics in radiation oncology and its potential importance for optimizing treatment.Prostatic neoplasmsRadiation therapyNeoplasm metastasisAndrogen antagonistsprostate neoplasmcastration resistant