OBJECTIVES: Prolongation of survival or prevention of bone metastases are the main objectives of phase 3 studies in MPC patients refractory to hormone therapy or castration resistant (HRPC/CRPC). In addition to efficacy, PROs and tolerability should be assessed to define treatment benefit, as PROs (eg. quality of life [QOL] and pain response) measure the patient’s subjective experience and can be correlated with hard outcomes (eg, pain intensity and survival). A systematic review evaluated the number of studies reporting PROs in HRPC/CRPC; tolerability was a secondary objective. METHODS: A predefined search strategy was used (2007-2011) in Medline, EMBASE, Cochrane Library, conference proceedings (ASCO/ESMO), AHRQ, NICE, and NHS HEED. Controlled clinical trials, retrospective cohort studies, and literature reviews were included. Studies in children, non-English language studies, case reports/series, and studies with preliminary/incomplete results were excluded. RESULTS: Of 79 studies identified, only 14 (18%) evaluated PROs and tolerability. The most common PRO was pain, measured using the Present Pain Intensity (PPI) instrument. Abiraterone showed statistically significant improvements in survival and pain response. Cabazitaxel did not show improvement in pain response, despite survival benefit. Bone-targeted agents (zoledronic acid/denosumab) prolonged the time to first on-study skeletal related event (SRE) but did not assess PROs. Radium-223, a new bone-targeted radiopharmaceutical agent emitting α-particles, included QOL as a secondary endpoint and showed survival benefit. Toxicities of the new therapies also require careful consideration. Fluid retention, hypertension, and hypokalemia are characteristic toxicities with abiraterone (predominately Grade 1/2). Cabazitaxel has a high incidence of Grade 3/4 neutropenia (82%), febrile neutropenia (8%), and diarrhea (6%).  Radium-223 is well tolerated with a low incidence of Grade 3/4 neutropenia (2%). CONCLUSIONS: PROs are incorporated in studies of new therapies for MPC, although mainly as secondary endpoints with delayed reporting of results. Therefore, safety profiles play an important role in individualized treatment selections.