ABSTRACT: CONTEXT:Some of the high costs of robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and proton beam therapy may be offset by better outcomes or less resource use during the treatment episode. OBJECTIVE:To systematically review the literature to identify the key economic trade-offs implicit in a particular treatment choice for prostate cancer. EVIDENCE ACQUISITION:We systematically reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and protocol. We searched Medline, Embase, and Web of Science for articles published between January 2001 and July 2016, which compared the treatment costs of RARP, IMRT, or proton beam therapy to the standard treatment. We identified 37, nine, and three studies, respectively. EVIDENCE SYNTHESIS:RARP is costlier than radical retropubic prostatectomy for hospitals and payers. However, RARP has the potential for a moderate cost advantage for payers and society over a longer time horizon when optimal cancer and quality-of-life outcomes are achieved. IMRT is more expensive from a payer's perspective compared with three-dimensional conformal radiotherapy, but also more cost effective when defined by an incremental cost effectiveness ratio <$50 000 per quality-adjusted life year. Proton beam therapy is costlier than IMRT and its cost effectiveness remains unclear given the limited comparative data on outcomes. Using the Grades of Recommendation, Assessment, Development and Evaluation approach, the quality of evidence was low for RARP and IMRT, and very low for proton beam therapy. CONCLUSIONS:Treatment with new versus traditional technologies is costlier. However, given the low quality of evidence and the inconsistencies across studies, the precise difference in costs remains unclear. Attempts to estimate whether this increased cost is worth the expense are hampered by the uncertainty surrounding improvements in outcomes, such as cancer control and side effects of treatment. If the new technologies can consistently achieve better outcomes, then they may be cost effective. PATIENT SUMMARY:We review the cost and cost effectiveness of robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and proton beam therapy in prostate cancer treatment. These technologies are costlier than their traditional counterparts. It remains unclear whether their use is associated with improved cure and reduced morbidity, and whether the increased cost is worth the expense.