Key clinical point: The data suggest advanced prostate cancers (PCa) with cyclin-dependent kinase 12 (CDK12) mutations display aggressive clinical behavior, highlighting the need to fully delineate the molecular and clinical characteristics, and appropriate therapeutic approaches for distinct subtypes of advanced PCa.
Major finding: Patients with CDK12 mutant PCa showed shorter time to metastasis and development of castration-resistant disease, compared with other genomic subtypes, with shorter time to prostate-specific antigen progression on first-line androgen receptor pathway inhibitor treatment of metastatic castration-resistant disease.
Study details: The Kaplan-Meier method was used with patients who were stratified by mutation status, to evaluate time to event outcomes.
Reimers MA, et al. Eur Urol. 2019 Oct 20. doi: 10.1016/j.eururo.2019.09.036.
Over the last several years, genomic-based studies have revealed numerous mutations and variants in prostate cancer. These studies have recently begun to include cyclin-dependent kinase 12 (CDK12). CDK12 has functions in transcriptional regulation, RNA splicing, and DNA damage repair in the cell. In this retrospective, genomic, correlative study, the investigators found that CDK12 mutations, which predominantly result in CDK12 loss, were associated with a shorter time to metastases and development of castrate-resistant disease, compared with other genomic subtypes. This finding supports the notion that CDK12-mutant prostate cancer may be a unique subtype to consider when planning future clinical trials.—Mark A. Klein, MD