Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy.

Metastasis-directed therapy (MDT) is an emerging treatment option for metachronous oligometastatic castration-sensitive prostate cancer (omCSPC) and can delay time to progression and the need to initiate androgen deprivation therapy (ADT). However, optimal ways to synergize MDT and ADT are not known, and better personalization of MDT is needed. We examined the role of combined ADT and MDT and the ability of genomic alterations to provide prognostic and predictive information regarding response to MDT. We found that high-risk (HiRi) mutations in TP53, BRCA1/2, ATM, and Rb1 are poor prognostic markers in omCSPC. In addition, patients harboring HiRi mutations experienced greater benefit from addition of ADT to MDT, indicating that these alterations are predictive biomarkers for treatment intensification. Our results suggest that genetic biomarkers might aid in treatment personalization for patients with omCSPC.