Volume 16, Number 3Review ArticlesThe Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate CancerTreatment ReviewNeal D ShoreRaoul S ConcepcionChristopher M PieczonkaVladimir MouravievNeil MariadosRobert B SimsMark EmbertonImmunotherapy encourages the recipient’s own immune response to destroy cancer cells, and current evidence suggests that immunotherapies may be most beneficial in early metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first therapeutic cancer vaccine to be approved by both the US Food and Drug Administration and European Medicines Agency for the treatment of asymptomatic or minimally symptomatic mCRPC. Combining immunotherapy with other treatments may have potent anticancer effects; cytoreductive therapies can release tumor antigens and promote a proinflammatory environment that could augment immunotherapies. However, some cytoreductive agents or coadministered drugs may be immunosuppressive. Understanding these interactions between different mCRPC treatment modalities may offer further potential to improve patient outcomes. [Rev Urol. 2014;16(3):122-130 doi: 10.3909/riu0637] © 2014 MedReviews®, LLCProstate cancerSipuleucel-TCombination therapy