Most of the updates in the 2015 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer center on the systemic therapy front, with a host of newer agents in the mix. At the NCCN 20th Annual Conference, Dr. Andrew J. Armstrong discussed some of the key developments in metastatic castration-resistant and castration-sensitive prostate cancer, particularly the conflicting results on repurposing docetaxel in castration-sensitive disease, the specific population who may experience greater survival benefit from immunotherapy in castration-resistant disease, updated data on the use of androgen receptor and biosynthesis inhibitors, and the emerging role of AR-V7 (androgen-receptor splice variant 7 messenger RNA) as a biomarker of treatment response.