Prednisolone is used quite extensively in clinical work as a second-line agent for endocrine treatment of destructive resistant prostate cancer (CRPC). Other steroid hormones, such as hydrocortisone and dexamethasone, are equally effective in CRPC. However, it is still inconclusive whether the efficacy between these drugs is the same. Recently, Ramachandran et al. from the University of Suffolk, UK, compared the efficacy of prednisolone and dexamethasone in CRPC and found that dexamethasone was more effective than prednisolone and that dexamethasone may be preferred clinically for the treatment of CRPC. the article was published in a recent issue of European Urology. The study included 82 patients with CRPC who were not receiving chemotherapy. Patients were randomized to three groups: the intermittent dexamethasone group (8 mg twice daily for 3 days every 3 weeks, 7 patients), the daily dexamethasone group (0.5 mg once daily, 39 patients), and the prednisolone group (5 mg twice daily, 36 patients). Patients in the prednisolone group were crossed over to dexamethasone at the onset of PSA progression. The primary measures were PSA response rate (50% decrease in serum PSA), time to PSA progression, objective response rate (based on the Real Efficacy Criteria for Solid Tumors, RECIST), and safety. The trial was terminated due to the absence of antitumor effects in the intermittent dexamethasone group. In the intention-to-treat analysis, the PSA response rate was 41% in the daily dexamethasone group and 22% in the prednisolone group. Among evaluable patients, PSA response rates were 47% and 24% in the dexamethasone and prednisolone groups, respectively, with median PSA progression times of 9.7 and 5.1 months (HR: 1.6). Twenty-three of the prednisolone group required crossover dexamethasone for PSA progression, and 19 were available for PSA assessment, of whom 7 (37%) showed a decrease in PSA on dexamethasone. The objective response rates according to RECIST criteria were 15% and 6% in the dexamethasone and prednisolone groups, respectively. There was no significant difference in toxicity between the two groups. In conclusion, the efficacy of dexamethasone in CRPC is higher than that of prednisolone, and the choice of prednisolone as a steroid treatment for CRPC is questionable, considering the higher antitumor activity of dexamethasone. In the absence of clear clinical trial data, the authors concluded that 0.5 mg daily dexamethasone is the standard regimen for CRPC patients requiring steroid monotherapy. The combination of prednisolone with abiraterone, docetaxel, and cabazitaxel has been widely used in patients with CRPC, and the effect of dexamethasone in combination with these drugs needs to be further investigated.