In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Early studies suggested androgen receptor (AR) splice variants might contribute to the progression of prostate cancer (PCa) into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR) and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown) cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrated the in vivo therapeutic effects of ASC-J9 by showing the inhibition of PCa growth using the xenografted model of CWR22Rv1 cells orthotopically implanted into castrated nude mice with undetectable serum testosterone. These results suggested that targeting both fAR- and AR3-mediated PCa growth by ASC-J9 may represent the novel therapeutic approach to suppress castration-resistant PCa. Successful clinical trials targeting both fAR and AR3 may help us to battle castration-resistant PCa in the future.

Objectives: To measure health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer. Methods: A total of 154 patients who underwent RP were included in this 5-year longitudinal survey. The Short Form 36-Item Health Survey, the University of California, Los Angeles, Prostate Cancer Index and the International Prostate Symptom Score questionnaires were administered at diagnosis and nine times afterwards. Results: Patients undergoing RP showed problems in some physical domains of general HRQOL, but these problems diminished over time. Mental health and social functions significantly improved during the follow-up period. The urinary function substantially declined at 3 months and continued to recover gradually but never returned to baseline. Most patients (95%) recovered to their baseline urinary bother score within 60 months. The overall mean total International Prostate Symptom Score progressively improved with time. On the other hand , at 60 months after RP, only 34% of subjects had fully returned to baseline sexual function. By 5 years postoperatively, 78% of the men had reached baseline sexual bother and the mean recovery time was 8.6 months. Adverse effects of RP on sexual function and bother were mitigated by bilateral nervesparing procedures up to 5 years after the operation. Conclusions: Despite reported problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months in our survey with functional outcomes remaining relatively stable in the majority of patients.Key words: longitudinal study, prostate cancer, quality of life, radical prostatectomy. IntroductionCurrently, the most common therapeutic options for localized prostate cancer are radical prostatectomy (RP), external radiation, and interstitial brachytherapy. RP is considered an especially safe and effective treatment for localized prostate cancer and has gained popularity among Japanese urologists over the last decade.1 As prostate cancer is increasingly diagnosed at early stages and therefore with more favorable survival outcomes, the basis on which patients select primary therapy has shifted toward considerations of health-related quality of life (HRQOL). 2,3Accordingly, HRQOL assessment has become an important form of outcome-based research that may weigh heavily on the justification of health care expenditures and the treatment selection by patients.Several assessments of HRQOL after prostate cancer treatment have been limited to studies of non-Hispanic whites, African-Americans, and Hispanics in the USA.4,5 Previously, we detailed HRQOL recovery in Japanese men with localized prostate cancer followed for 2 years after RP. 6 In the current analysis we assessed temporal changes in HRQOL up to 5 years following RP using validated questionnaires. To our knowledge the current study is the longest-term prospective study to assess the impact of RP on general and disease-specific outcomes following RP in Japanese men with clinically localized prostate can...