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Background It remains uncertain whether those with response to antiandrogen withdrawal (AAW) have a better prognosis. We investigated the predictors of a better response to AAW and overall survival after acquiring resistance to first-line androgen deprivation therapy inpatients with castration-resistant prostate cancer (CRPC). Patients and Methods We retrospectively reviewed the medical records of 87 CRPC patients treated at Keio University Hospital. Sixty-seven of 87 CRPC patients underwent AAW. We analyzed clinicopathologic parameters to identify predictors of survival in CRPC patients and investigated predictors of good response to AAW. Results Younger age, longer duration of androgen deprivation therapy before CRPC development, and better response to AAW were independent favorable prognostic factors for overall survival. Although better response to AAW was a favorable prognostic factor in this study, trying AAW was not significantly related to overall survival. Duration of hormone therapy was significantly longer in those whose disease responded to AAW (69.9 ± 11.0 months) than those with no response (45.3 ± 5.2 months). Conclusion The prognostic benefit of AAW was not clearly determined in this study. However, AAW might be beneficial in patients who have favorable prognostic factors for a response to AAW—that is, those who have received hormone therapy for a long period. However, AAW should not be done in patients who do not have favorable factors and who had a high prostate-specific antigen level at the time of their prostate cancer diagnosis.

An 82-year-old male who presented with the chief complaint of gross hematuria and a history of prostate cancer treated with brachytherapy 6 years previously is described. Cystoscopy revealed multiple bladder tumors on the right posterior wall. A transurethral resection of the bladder tumor was performed and a pathological diagnosis of the inverted papilloma was made. To the best of our knowledge, this case is the first report of bladder-inverted papilloma after brachytherapy for prostate cancer.

The purpose of this study was to evaluate the efficacy of tegafur-uracil (UFT) administration as a fourth-line therapy in patients with castration-resistant prostate cancer (CRPC) who had already received combined androgen blockade (CAB) therapy (first-line), alternative antiandrogen therapy (second-line), and estramustine phosphate sodium hydrate (EMP) therapy (third-line), in order to determine who would benefit from UFT therapy.UFT was administered at a daily dose of 300 mg/m(2) to 26 patients, and the response to UFT 4 weeks after its induction and its toxicity were evaluated.A reduction in the serum prostate-specific antigen (PSA) value was observed in 12 patients (46.2 %), while two cases (7.7 %) achieved more than 50 % reduction in PSA. Two patients (7.7 %) required discontinuation of UFT administration because of side effects (grade 2 exanthema in one patient and grade 2 nausea in one patient). A PSA response to UFT was observed, especially in patients older than 75 years and/or whose Gleason score was 8 or less.Our data indicate that UFT administration as a fourth-line therapy was tolerable and effective to some degree in patients with CRPC who had already received CAB therapy, alternative antiandrogen therapy, and EMP therapy. It can be used, even in patients aged more than 75 years old, without any loss of efficacy or effect on their activities of daily life, and can be regarded as a treatment option for patients with advanced prostate cancer.

This retrospective chart review study was conducted to evaluate the efficacy of estramustine phosphate sodium hydrate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC) and to determine who would benefit from EMP therapy. EMP was administered at a daily dose of 560 mg to 102 patients as a third-line therapy, who had already received combined androgen blockade (CAB) and subsequent alternative antiandrogen therapy. The responses to EMP after its induction and its toxicity were evaluated. We also analyzed the association between the clinicopathological factors of the patients and their responses to EMP therapy. A reduction in the serum prostate-specific antigen (PSA) 4 weeks after induction was observed in 70 patients (68.6%), while 30 cases (29.4%) achieved more than 50% reduction of PSA. Long-term reduction of PSA from baseline for more than 6 months was observed in 31 patients (30.4%). EMP treatment was discontinued in 11 patients (10.8%) because of side effects (nausea in six patients, gynecomastia in three patients, eruption in one patient, and liver dysfunction in one patient). Multivariate analysis demonstrated that long duration of prior hormonal therapy was an independent favorable factor for reduced PSA levels, long responses, and overall survival. The data suggest that oral EMP administration as a third-line monotherapy is well tolerated and effective to some degree in patients with CRPC who have already received CAB and subsequent alternative antiandrogen therapy. Thus, EMP can be regarded as one treatment option, especially for patients whose prior duration of hormonal therapy was long.

This study was designed to detect the factors that were significantly associated with the results of anti-androgen withdrawal (AAWD) therapy, and to examine whether patients with aggressive prostate cancer demonstrating a short prostate-specific antigen (PSA)-doubling time (DT) could benefit from it without even greater exacerbation of the disease. We conducted a retrospective chart review study of 121 patients who received AAWD therapy due to failed combined androgen blockade (CAB) therapy. A reduction in the serum PSA level after AAWD was observed in 35 patients (28.9 %), and a greater than 50 % decrease from the baseline serum PSA level was observed in 16 patients (13.2 %). Shortening of PSA-DT after AAWD was observed in 48 patients (39.7 %). Univariate and multivariate analyses demonstrated that only a long duration of prior anti-androgen treatment was selected as a significant predictor for a good response to AAWD therapy. With respect to exacerbation after AAWD, we found that patients with a short baseline PSA-DT conversely had a low risk of subsequent shortening of PSA-DT. Using these two factors, we could stratify the patients into four groups, and patients with prior duration of anti-androgen >18 months and PSA-DT ≤3 months demonstrated the best results with a good response rate (67.9 %) and a low risk for a worsening of the disease (14.3 %). We conclude that AAWD would be effective especially for patients whose cancer progressed rapidly (short PSA-DT) after a long stable period under CAB and should be recommended before embarking on the next therapeutic maneuver.

INTRODUCTION AND OBJECTIVES: Antiandrogen withdrawal (AAWD) is a potential therapeutic maneuver for treating patients with castration-resistant prostate cancer (CRPC) who have undergone a combined antiandrogen blockade (CAB) therapy. However, clinicians are also concerned that, for patients with aggressive CRPC demonstrating a short PSA doubling time (PSADT), discontinuation of antiandrogens may result in even greater exacerbation of the disease. This study was designed to examine the safety of AAWD therapy. METHODS: We reviewed the medical records of patients with CRPC who received prior initial treatment with CAB therapy during the period of 2001-2011. In 95 patients, AAWD therapy (68 patients previously received bicalutamide, and 27 patients flutamide) for CRPC was performed, and we examined the changes in PSADT before and after AAWD. Serum PSA determinations were obtained 4 weeks before stopping antiandrogen therapy, immediately before (baseline PSA level), and every 4 weeks thereafter. RESULTS: A reduction in the serum PSA level after AAWD was observed in 29 of 95 patients (30.5%), and a greater than 50% decrease from the baseline serum PSA level was observed in 11 patients (10.5%). The median response duration in these 29 responders was 4.0 months. In the 66 non-responders, the mean PSADT before and after AAWD was 7.7 and 6.2 months, respectively. A shortening of PSADT after AAWD was observed in 37 patients (38.9%). Next, using a logistic regression model with stepwise forward selection, we performed univariate and multivariate analyses to identify predictors that have an influence on shortening of PSADT after AAWD (Table below). Interestingly, the results indicated that patients with a short PSADT (aggressive disease) before AAWD had a low risk of subsequent shortening of PSADT after AAWD. In 25 patients with baseline PSADT 2 months, a shortening of PSADT after AAWD was observed in only 3 patients (12.0%). Furthermore, 8 of the 25 patients (32.0%) responded to the AAWD therapy, and 2 patients (8.0%) achieved a greater than 50% decrease from the baseline PSA level. CONCLUSIONS: Our data indicate that patients with a short baseline PSADT (aggressive disease) had a low risk for worsening of the disease by AAWD, and we concluded that it should be recommended for all patients with CRPC before embarking on the next therapeutic maneuver.