Emmanuel Antonarakis, MBBCh, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, highlights the clinical and genomic features of SPOP mutations in prostate cancer. SPOP mutations occur in 6-15% of patients with prostate cancer. Previous studies have found that patients with SPOP mutations have superior responses to androgen deprivation therapy (ADT) and a more favorable response to abiraterone compared to patients with wild-type SPOP. A retrospective analysis of 59 patients with prostate cancer, who also had SPOP mutations, found that clinical outcomes to first-line ADT were longer than expected for a genomically-unselected cohort of patients. SPOP mutations appeared to be mutually exclusive with ERG fusions. This interview took place during the 2021 Genitourinary Cancers Symposium.