Reimers MA, Yip SM, Zhang L, et al. - A retrospective analysis was done of data from three academic medical centers, including 317 individuals with advanced prostate cancer and former next-generation sequencing from tumor tissue (n = 172) or circulating tumor DNA (n = 145) in order to ascertain the clinical course of individuals with Cyclin-dependent kinase 12 (CDK12) mutant advanced prostate cancer, in comparison with other genomic subtypes. In contrast with other genomic subtypes, with shorter time to PSA progression on first-line androgen receptor pathway inhibitor treatment of metastatic castration-resistant disease, individuals with CDK12 mutant prostate cancer showed a shorter time to metastasis and development of the castration-resistant disease. In contrast with other mutation subgroups, CDK12 mutant individuals did not have an overall shorter time on treatment, and in multivariate analysis, CDK12 status did not illustrate statistical importance. In conclusion, the data imply that advanced prostate cancers harboring CDK12 mutations exhibit aggressive clinical behavior, emphasizing the necessity to fully describe the molecular and clinical features, and relevant therapeutic strategies for different subtypes of advanced prostate cancers.