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Background: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone‐sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). Methods: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan–Meier method was used to assess oncological outcomes, including time to castration‐resistant prostate cancer (CRPC), progression‐free survival 2 (PFS2, duration from initial treatment to tumor progression during second‐line treatment), cancer‐specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. Results: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan–Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3–4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Conclusions: Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first‐line treatment option given its superior oncological outcomes. [ABSTRACT FROM AUTHOR]

Purpose: No study has compared cancer regression (d) and growth (g) rates in patients with advanced castration-sensitive prostate cancer (CSPC) treated with androgen deprivation therapy. The comparison of d and g rates provides insight into the differential impact of ADT regimens on tumor dynamics, potentially guiding more personalized treatment strategies. Therefore, we aimed to estimate these rates and evaluate their impact on survival outcomes. Methods: Sequential prostate-specific antigen (PSA) data was obtained from the KYUCOG-1401 trial including patients with advanced CSPC randomized to gonadotropin-releasing hormone (GnRH) antagonist (group A) and GnRH agonist plus bicalutamide (group B). d and g rates were estimated by applying mathematical models and were compared in subgroups. PSA-progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were compared by lower and higher than the median of these rates. Results: Patients with higher PSA and higher extent of disease score at enrollment presented higher d rates (0.03965 vs. 0.03546, p = 0.0006) and (0.03947 vs. 0.03587, p = 0.0113) for groups A and B, respectively. The median d rate was lower for group A than group B (0.03306 vs. 0.039965, respectively [p = 0.0002]). The median g rate was higher for group A than group B (0.00016 vs. 0.00002, respectively [p = 0.0014]). The g rate, but not the d rate discriminated PSA-PFS, rPFS, and OS. Conclusion: Our results suggest that GnRH agonist plus bicalutamide reduced PSA level faster and suppressed PSA rising longer than GnRH antagonist. Moreover, measuring the g rate can predict PSA-PFS, rPFS, and OS in patients with advanced CPSC treated with androgen deprivation therapy. These findings suggest that incorporating g rate measurements into clinical practice could improve prognostic accuracy and guide treatment decisions in advanced CSPC. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e., luteinizing hormone-releasing hormone agonist and/or AR antagonists) to R/M SDC patients. However, only a subset of patients benefits from such treatments. We have shown that response to CAB is associated with steroid 5α-reductase 1 (SRD5A1) mRNA expression. SRD5A1 catalyses the intracellular conversion of testosterone into the more potent AR-agonist dihydrotestosterone. This conversion can be inhibited by dutasteride, a potent SRD5A1-inhibitor, which is currently prescribed for benign prostatic hyperplasia. We hypothesize that repurposing dutasteride to target AR signalling in SDC could enhance therapeutic response and clinical outcome in SDC patients. Methods: This prospective, open-label, randomized controlled phase II clinical trial, is designed to investigate whether dutasteride as an adjunct drug to CAB improves response rate and clinical outcome in patients with AR-positive R/M SDC. Patients are divided in two cohorts based on their prior systemic treatments. In cohort A, CAB-naïve patients (n = 74) will be randomly assigned to either a control arm (Arm 1) receiving CAB (goserelin 10.8 mg/3m and bicalutamide 50 mg/OD) or an experimental arm (Arm 2) where dutasteride (0.5 mg/OD) is added to the CAB regimen. In cohort B, patients with disease progression after adjuvant or first-line palliative CAB therapy (max. n = 24) will receive goserelin, bicalutamide, and dutasteride to assess whether the addition of dutasteride can overcome therapy resistance. The primary endpoints are the objective response rate and duration of response. Secondary endpoints are progression-free survival, overall survival, clinical benefit rate, quality of life, and safety. Translational research will be performed to explore molecular target expression differences and their correlation with clinical outcome. Discussion: The DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial's findings could be readily applied into clinical practice. Trial registration: Clinicaltrials.gov Identifier: NCT05513365. Date of registration: August 24, 2022. Protocol version: Current protocol version 4.0, February 21, 2024. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront novel androgen receptor signaling inhibitors (ARSIs) are the first-line treatment for metastatic castration-sensitive prostate cancer (mCSPC). However, there are a certain number of cases in which androgen deprivation therapy (ADT) is more effective in patients of Asian descent. If we can identify patients who show a marked response to ADT within 12 weeks after ADT, which is the inclusion criterion for upfront ARSI clinical trials, it would be valuable from an economic standpoint. A total of 218 patients who received ADT treatment at Kanazawa University Hospital between 2000 and 2020 were included in this study. Multivariate analysis revealed that a decrease in PSA levels of <95% at 12 weeks after ADT initiation was a predictor of short time to castration resistance (TTCR) in low-risk patients. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs, based on the rate of PSA reduction at 12 weeks. Background: The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. Methods: A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan–Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. Results: The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. Conclusion: The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w. [ABSTRACT FROM AUTHOR]

Abstract Background Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e., luteinizing hormone-releasing hormone agonist and/or AR antagonists) to R/M SDC patients. However, only a subset of patients benefits from such treatments. We have shown that response to CAB is associated with steroid 5α-reductase 1 (SRD5A1) mRNA expression. SRD5A1 catalyses the intracellular conversion of testosterone into the more potent AR-agonist dihydrotestosterone. This conversion can be inhibited by dutasteride, a potent SRD5A1-inhibitor, which is currently prescribed for benign prostatic hyperplasia. We hypothesize that repurposing dutasteride to target AR signalling in SDC could enhance therapeutic response and clinical outcome in SDC patients. Methods This prospective, open-label, randomized controlled phase II clinical trial, is designed to investigate whether dutasteride as an adjunct drug to CAB improves response rate and clinical outcome in patients with AR-positive R/M SDC. Patients are divided in two cohorts based on their prior systemic treatments. In cohort A, CAB-naïve patients (n = 74) will be randomly assigned to either a control arm (Arm 1) receiving CAB (goserelin 10.8 mg/3m and bicalutamide 50 mg/OD) or an experimental arm (Arm 2) where dutasteride (0.5 mg/OD) is added to the CAB regimen. In cohort B, patients with disease progression after adjuvant or first-line palliative CAB therapy (max. n = 24) will receive goserelin, bicalutamide, and dutasteride to assess whether the addition of dutasteride can overcome therapy resistance. The primary endpoints are the objective response rate and duration of response. Secondary endpoints are progression-free survival, overall survival, clinical benefit rate, quality of life, and safety. Translational research will be performed to explore molecular target expression differences and their correlation with clinical outcome. Discussion The DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial’s findings could be readily applied into clinical practice. Trial registration Clinicaltrials.gov Identifier: NCT05513365. Date of registration: August 24, 2022. Protocol version Current protocol version 4.0, February 21, 2024.

Objectives: To compare the effectiveness and safety of gonadotropin‐releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone‐sensitive prostate cancer (HSPC). Methods: The study was conducted as KYUCOG‐1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression‐free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression‐free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. Results: PSA progression‐free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01–1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59–1.08, p = 0.146). No significant differences were observed in radiographic progression‐free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. Conclusions: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer. Methods We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment. Results The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common. Conclusions Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment. Trial registration: UMIN000018964, CRB6180007.

Introduction: Salivary duct carcinoma (SDC) is a rare, high-grade salivary gland malignancy. Recently, targeting the androgen receptor (AR) is one of the most promising new therapeutic strategies for AR-positive SDC. Case Review: In this report, a 70-year-old man who was diagnosed with an AR-positive SDC underwent androgen deprivation therapy (ADT) as a treatment for recurrence after primary therapy. The ADT well contributed to control of SDC; however, the patient was referred to urologists for urinary hesitancy and slow flow and he was diagnosed as having castration-resistant prostate cancer. Literature Review: Since SDC is a rare disease, it has been difficult to establish the most effective therapy. Nevertheless, several papers have reported the clinical benefit of ADT for AR-positive SDC, and the latest version of the National Comprehensive Cancer Network guidelines also states the importance of assessing for the presence of AR in SDC. On the other hand, in the field of urology, it is also known that although ADT is initially effective in prostate cancer patients, prostate cancer often develops into castrate-resistant prostate cancer due to the adaptation of prostate cancer cells to ADT for survival and growth. Conclusion: We reported a case of castrate-resistant prostate cancer diagnosed during the ADT for metastatic SDC. The present case emphasizes the importance of screening for prostate cancer at the initiation of ADT treatment and during treatment. [ABSTRACT FROM AUTHOR]

Abstract Objectives The objective of the study is to compare the efficacy and safety of alternative androgen therapy (AAT) with enzalutamide + androgen deprivation therapy (ADT) and flutamide + ADT in the treatment of Japanese men with metastatic or nonmetastatic castration‐resistant prostate cancer (CRPC) who progressed despite combined androgen blockade (CAB) with bicalutamide + ADT. AAT treatment sequence was also investigated. Materials and methods The open‐label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016 to March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375mg/day [125mg three times daily]) + ADT (flutamide first) as first‐line therapy. Following prostate‐specific antigen (PSA) progression, other disease progression, or discontinuation of first‐line therapy due to an adverse event (AE), patients switched to the other treatment as second‐line therapy. The primary endpoint was time to PSA progression with first‐line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second‐line therapy). AEs were monitored to assess safety. Results Overall, 206 men were randomized (enzalutamide first, n = 102; flutamide first, n = 104) and stratified by study site and disease stage; 133 patients transitioned to second‐line therapy (enzalutamide first, n = 48; flutamide first, n = 85). TTPP1 was significantly improved with enzalutamide first versus flutamide first (median 21.4 months vs. 5.8 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] [0.29, 0.61]). TTPP2 was numerically improved with enzalutamide first versus flutamide first (median not reached vs. 21.2 months; HR 0.76; 95% CI [0.48, 1.19]). Both treatments were generally well tolerated, with AEs consistent with their known safety profiles. Conclusion First‐line AAT with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT. Enzalutamide + ADT may therefore be the preferred first‐line AAT option in Japanese men with metastatic or nonmetastatic CRPC who progress despite CAB with bicalutamide + ADT.

Background: Patient-reported outcome (PRO) measures can provide valuable information in evaluating patients' health-related quality of life (HRQoL). Post hoc analysis of the AFTERCAB study was conducted to evaluate the HRQoL benefit of enzalutamide plus androgen deprivation therapy (ADT) compared to flutamide plus ADT for the treatment of patients with castration-resistant prostate cancer (CRPC) in Japan. Methods: The open-label AFTERCAB study was conducted from November 2016 to March 2020 in Japanese men aged ≥ 20 years with asymptomatic or mildly symptomatic CRPC. Patients received enzalutamide plus ADT or flutamide plus ADT, respectively, as first-line alternative androgen therapy (AAT). HRQoL was analyzed through the Functional Assessment of Cancer Therapy–Prostate, EuroQoL 5-Dimension 5-Level instruments, Brief Pain Inventory–Short Form, and Brief Fatigue Inventory. The longitudinal changes in HRQoL, HRQoL deterioration based on minimally important difference (MID), and time to HRQoL deterioration were evaluated for first-line AAT. Results: Overall, HRQoL between the enzalutamide and flutamide groups was similar during first-line treatment. No statistically significant HRQoL difference in change from baseline to week 61 (least square mean difference; p value) was observed. Furthermore, proportions of pain progression, symptom worsening, and HRQoL deterioration based on MID, were not significantly different between groups. Conclusions: The results were similar in all subscales of each PRO, demonstrating similar HRQoL deterioration based on MID criteria between the enzalutamide and flutamide groups. [ABSTRACT FROM AUTHOR]

Background: The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer.Methods: We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment.Results: The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common.Conclusions: Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment.Trial Registration:  UMIN000018964, CRB6180007. [ABSTRACT FROM AUTHOR]

Androgen-deprivation therapy is an extremely effective treatment for progressive prostate cancer. Previously, the first-line treatment for progressive prostate cancer was combined androgen blockade (CAB). If the disease progressed to castration-resistant prostate cancer, the administration of androgen receptor signaling inhibitors (ARSIs) was recommended. When elevated serum prostate-specific antigen (PSA) levels are seen during CAB treatment, it is important to suspect antiandrogen withdrawal syndrome (AWS), discontinue CAB, and monitor the changes in the serum PSA levels. If a reduction in the patient's PSA levels is subsequently observed, antiandrogens should be discontinued and the patient should be followed, but if their PSA level rises they should be transitioned to ARSI treatment. Recently, there have been reports of withdrawal syndrome (WS) after ARSI treatment. With the increased use of ARSIs, such as abiraterone acetate, enzalutamide, apalutamide, and dalorutamide, it is necessary to consider ARSI WS when a patient's serum PSA level increases during ARSI treatment. Unnecessary treatment can be avoided if the confirmation of ARSI WS is prioritized. Conversely, if it is not confirmed there is a risk that second-line treatment will be delayed. This is a review of recent studies of ARSI WS. It also discusses future prospects in this field., Competing Interests: The Author has no conflicts of interest in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Objective: To determine the effect of combined androgen blockade with a first‐generation anti‐androgen on the prognoses of metastatic hormone‐sensitive prostate cancer patients stratified by tumor burden. Methods: We retrospectively analyzed the cases of metastatic hormone‐sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008–2017 at 30 institutions in Japan. To compare the overall survival and progression‐free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High‐burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. Results: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low‐ and high‐burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between‐group difference in the overall survival according to the androgen deprivation therapy method, in the high‐burden group the progression‐free survival of the combined androgen blockade‐treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34–0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60–0.98. Conclusion: In the high‐burden group, combined androgen blockade with a first‐generation anti‐androgen resulted in superior progression‐free survival compared with castration monotherapy. For well‐selected metastatic hormone‐sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios. [ABSTRACT FROM AUTHOR]

Background: Combining abiraterone (Abi) with androgen deprivation therapy (ADT) improves overall survival, compared to ADT only, in patients with metastatic castration-sensitive prostate cancer (mCSPC). In Japan, bicalutamide (Bica) and ADT (combined androgen blockade: CAB) is frequently provided for mCSPC. Because these two treatments have not been compared, mCSPC patients who received either treatment were retrospectively analyzed. Methods: Of 178 patients with LATITUDE high-risk mCSPC, 103 had received ADT plus upfront Abi (Abi group) and 75 had received ADT plus Bica (Bica group) in multiple institutions of the Tokai Urologic Oncology Research Seminar. Kaplan–Meir curves were used to retrospectively analyze survival and cancer recurrence. Univariate and multivariate Cox regression analyses identified potential prognostic factors for progression-free survival (PFS). Results: Significant differences in major clinicopathological characteristics between the two groups were not observed. The rate of castration-resistant development was higher in the Bica compared to Abi group (50.6 vs. 25.2%, p < 0.001). The median PFS in the Bica group was 13.6 months {95% confidence interval [CI] 9.2–22.2}; however, in the Abi group, PFS did not reach the median {95% CI 18.5–not assessed [NA]; p < 0.001}. Time to second progression for the Abi group was superior (p = 0.07). Univariate and multivariate analyses revealed Gleason pattern 5, high alkaline phosphatase levels, and conventional CAB using Bica as significant prognostic factors for short PFS. Conclusions: In patients with LATITUDE high-risk mCSPC, upfront use of Abi combined with ADT resulted in favorable prognostic outcomes compared with conventional ADT with Bica. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score–matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2–89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score–matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2–89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background/Aim: There are several treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) in the world. In recent years, the use of docetaxel, abiraterone, enzalutamide, and apalutamide has been used for mHSPC, but combined androgen blockade (CAB) therapy using first-generation antiandrogens has been widely used in Japan. There is a background. We performed a consecutive study of patients who received combined androgen blockade (CAB) at a single institute to determine the prognostic factors for mHSPC. Patients and Methods: We conducted a consecutive study of 237 mHSPC patients treated with CAB from 2003 to 2017 at the Gunma University Hospital. Prostate-specific antigen progressionfree survival (PSA-PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The associations between pre-treatment risk factors and the PSA response 3 months after starting CAB, PSA-PFS, and OS were evaluated by the Cox proportional hazards model. Results: Among the 237 cases, the median PSA-PFS and OS times were 63.0 and 91.4 months, respectively. The median PSA-PFS and OS times of M1 cases (174 cases, 73.4% of all 237 cases) were 36.1 and 75.9 months, respectively. The Eastern Cooperative Oncology Group performance status (ECOG PS) score, hemoglobin (Hb), lactate dehydrogenase, extent of disease, visceral metastasis (no vs. yes), and PSA response after 3 months were significant predictors of OS according to Cox regression analysis of prognostic factors in M1 patients. The ECOG PS, Hb, visceral metastasis (no vs. yes), and PSA response after 3 months predicted OS high-risk patients in LATITUDE criteria. The OS was 92.1 months in the low-risk group (0-1 risk factors), 48.2 months in the intermediate-risk group (2 risk factors), and 16.9 months in the high-risk group (3-4 risk factors). Conclusion: CAB should be considered as a treatment option for strictly selected patients with mHSPC, even though novel treatments are available. [ABSTRACT FROM AUTHOR]

BackgroundAndrogen deprivation therapy (ADT) is essential in the treatment of advanced and metastatic prostate cancer. As the correlation between hormone therapy and hypertension remains unclear and prostate cancer is less prevalent in the Asian population, the clinician should focus on not only anticancer therapy but also the side effects of the intervention and quality of life of these patients.ObjectiveThis study aimed to investigate the risk of subsequent hypertension in patients undergoing androgen deprivation therapy for prostate cancer.Setting Data of 10,843 patients with prostate cancer were retrospectively collected from the Longitudinal Health Insurance Database of Taiwan. The institutional review board of Kaohsiung Medical University Hospital approved our study.Method In propensity score matching, 3001 patients with prostate cancer aged ≥ 40 years who underwent androgen deprivation therapy were included in the study cohort (androgen deprivation therapy-ever), and 3001 patients with cancer who did not undergo androgen deprivation therapy were included in the control group (androgen deprivation therapy-never), after adjusting for age and other comorbidities.Main outcome measure The event of new-onset hypertension between the study cohort and control cohort.ResultsDuring the average 5-year follow-up period, the incidence rates of new-onset hypertension were 22.6 and 33.0 per 1000 person-years in the androgen deprivation therapy-never and androgen deprivation therapy-ever cohorts, respectively. The androgen deprivation therapy-ever cohort was found to be 1.78 times more likely to develop new-onset hypertension than was the control group (95% confidence interval [CI], 1.61–1.96; P < 0.001). Moreover, the subgroup of combined androgen blockade had almost doubled the risk of subsequent hypertension (adjusted hazard ratio, 1.93; 95% CI 1.71–2.18; P < 0.001).ConclusionsOur study suggests that men with prostate cancer who underwent androgen deprivation therapy are at risk of developing hypertension in the future. [ABSTRACT FROM AUTHOR]

Abstract Background This study was performed to examine the usefulness of combined androgen blockade (CAB) therapy with a gonadotropin-releasing hormone (GnRH) antagonist (CAB-antagonist therapy), instead of CAB therapy with GnRH agonist (CAB-agonist therapy) against very high-risk prostate cancer (Pca). Methods We retrospectively studied 84 Pca patients with pretreatment prostate-specific antigen (PSA) level ≥ 50 ng/mL, who were pathologically diagnosed between January 2007 and December 2016. GnRH antagonist was administered to 34 patients and GnRH agonist was administered to 50 patients. All patients received concurrent antiandrogen treatment. The primary end point was PSA progression-free survival (PSA-PFS). Results PSA-PFS was significantly longer for the CAB-antagonist group compared to the CAB-agonist group (log-rank test, P

Background: Development of novel agents targeting the androgen axis has led to improved overall survival in castration-resistant prostate cancer (CRPC). This study aimed to investigate the optimal timing of treatment with one such agent, abiraterone acetate (AA), in Japanese patients. Materials and methods: Between July 2014 and February 2016, 106 CRPC patients were administered AA in Nagoya City University Hospital, Nagoya, Japan and in four affiliated hospitals following failure of primary combined androgen blockade (CAB). Of these, records of 69 patients treated before chemotherapy were retrospectively analyzed. Patients were divided into two AA treatment groups: (1) first- or second-line after diagnosis of CRPC, designated the Early Group, and (2) third-line onwards, designated the Deferred Group. Prostate-specific antigen (PSA) response rate, ≥ 50% PSA decline rate with treatment, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 was used to classify adverse events. Results: In 24 patients in the Early Group and 45 patients in the Deferred Group, no significant differences in baseline parameters were observed between groups. PSA response rate, ≥ 50% PSA decline rate and PFS (but not OS) were significantly better in the Early Group than in the Deferred Group. Serum aspartate aminotransferase/alanine aminotransferase elevations were the most common Grade 3 treatment-related toxicities, and were clinically manageable. In subgroup analyses of the Early Group, comparison of first-line AA with second-line AA after flutamide treatment showed no changes in PSA response rate, PFS, or OS. Conclusion: This study suggests improved favorable outcomes of first- or second-line AA treatment in Japanese chemotherapy-naïve CRPC patients after failed CAB; statistical confirmation of such improvement was evident for PFS, but not OS. In addition, early AA treatment exhibited an acceptable safety profile.

Purpose: Combined androgen blockade (CAB) and luteinizing hormone-releasing hormone (LHRH) agonist monotherapy are commonly used in androgen deprivation therapy (ADT). In this randomized clinical trial, we aimed to compare the two methods of ADT in terms of quality of life (QOL). Methods: Eighty patients who underwent primary ADT for newly diagnosed prostate cancer were randomly assigned to CAB group (Group 1) and LHRH agonist monotherapy group (Group 2). Leuprolide and anti-androgen (bicalutamide 50 mg) were used to minimize the confounding effects caused by medication. QOL was evaluated at baseline, 3 months and 6 months post-ADT using validated EORTC QLQ-C30, PR25, and depression questionnaires. A difference of > 10 points in the EORTC domain scores was defined as 'clinically significant'. Results: In the baseline characteristics, there was no significant difference between the two groups. At 3 months after ADT, Group 1 had significantly lower pain scores than Group 2 (p = 0.004), while Group 1 had significantly poorer diarrhea symptom score than Group 2, without clinical significance (p = 0.047). No significant differences were observed in the C30, PR25 domains, and the depression score at 3 months. At 6 months, the QOL scores of all the groups were similar. Conclusions: There was no difference in the patient's QOL, except that CAB group was associated with significantly better pain relief than LHRH agonist monotherapy at 3 months following ADT, which was not sustained thereafter. Our results suggest that the benefit of prolonged (≥ 3 months) CAB is questionable in terms of patients' QOL. [ABSTRACT FROM AUTHOR]

Advances made in the screening, diagnosis and management of prostate cancer have improved the survival rates of the patients. However, many of these treatments including surgery, radiotherapy, and pharmacotherapy, have an impact on the subsequent health-related quality of life (HRQoL) of these patients. Since it is an important prognostic factor of survival, failure to evaluate the HRQoL and its predictors in these patients typically results in long-term deficits in their overall well-being, that is, their physical, social, emotional, and mental health. The objective of this study was to evaluate the management and HRQoL among patients with prostate cancer at Kenyatta National Hospital.This was a descriptive cross-sectional study. The sample size of 62 patients who met the eligibility criteria was selected through simple random sampling on the respective clinic days of the cancer treatment centre and urology clinic. Data was collected through a pre-tested structured questionnaire and HRQoL tools which are EORTC-QLQ-C30 and EORTC-QLQ-PR25 and analysed using STATA version 13 software. Descriptive analysis was used to summarise the continuous and categorical variables. Spearman's rho (rs) correlation was used to determine the predictors of HRQoL based on the strength and significance of association at 0.05 level of significance.The mean age of the participants was 70.5 (±7.35) years. The majority (52, 83.9%) of the patients had a prostate specific antigen (PSA) above 20 ng/ml. Twenty-one (33.9%) were graded as Gleason group 5 and 41 (66.1%) had stage IV disease at diagnosis. Fifty (80.9%) participants were on hormonal therapy, with most of them being on combined androgen blockade. The overall HRQoL was 65.1. Fatigue, one of the major complaints among these patients, was negatively associated with physical functioning (p = 0.0005), role functioning (p = 0.0026), social functioning (p = 0.0001), financial difficulties (p = 0.0077) and quality of life (p = 0.0050).Fatigue was the most common predictor of poor HRQoL in several scales of measurement. For those on management, frequent assessment of HRQoL should be carried out and interventions instituted immediately. [ABSTRACT FROM AUTHOR]

Purpose To explore treatment patterns among patients with prostate cancer and bone metastasis and to compare clinical outcomes following use of different hormone therapies including combined androgen blockade (CAB), nonsteroidal antiandrogen (NSAA) monotherapy, and castration monotherapy. Methods: We conducted a population‐based cohort study using data from the Urban Employee Basic Medical Insurance database (2011‐2014) in Beijing. We identified 475 patients with newly diagnosed bone metastatic prostate cancer with at least one prescription for hormone therapy and described their treatment patterns over a median follow‐up of 20.7 months. Cox proportional hazards model was used to compare time to chemotherapy initiation between patients starting on different hormone therapies. Results: Hormone therapy and/or bisphosphonate therapy with zoledronic acid were the initial treatments in the majority of patients (87.8%); chemotherapy, radiotherapy, and surgery were usually given later in the treatment pathway. CAB was the most common hormone treatment (73.7%). For time to chemotherapy initiation, hazard ratios (95% confidence intervals) were 2.43 (1.08‐5.44) for NSAA alone vs CAB and 1.29 (0.78‐2.13) for castration alone vs CAB. Conclusions: Our findings show that while a wide range of therapies are used to treat patients with prostate cancer and bone metastasis in Beijing, hormone therapy and bisphosphonate therapy are the most commonly prescribed, and use of CAB was seen to be advantageous in delaying time to chemotherapy initiation over NSAA monotherapy. Future studies should explore longer‐term treatment patterns, including use of newly approved treatments. [ABSTRACT FROM AUTHOR]

Background: This study was performed to examine the usefulness of combined androgen blockade (CAB) therapy with a gonadotropin-releasing hormone (GnRH) antagonist (CAB-antagonist therapy), instead of CAB therapy with GnRH agonist (CAB-agonist therapy) against very high-risk prostate cancer (Pca).Methods: We retrospectively studied 84 Pca patients with pretreatment prostate-specific antigen (PSA) level ≥ 50 ng/mL, who were pathologically diagnosed between January 2007 and December 2016. GnRH antagonist was administered to 34 patients and GnRH agonist was administered to 50 patients. All patients received concurrent antiandrogen treatment. The primary end point was PSA progression-free survival (PSA-PFS).Results: PSA-PFS was significantly longer for the CAB-antagonist group compared to the CAB-agonist group (log-rank test, P <  0.01) in Pca patients with more than six bone metastases (the extent of disease [EOD] grade 2-4). On multivariate analysis, CAB-antagonist therapy was shown to be a possible prognostic factor for PSA-PFS (adjusted hazard ratio: 0.41, 95% confidence interval: 0.16-0.90, P = 0.03).Conclusions: CAB-antagonist therapy may be a useful option in bone metastatic Pca patients with EOD grade 2-4. [ABSTRACT FROM AUTHOR]

Background: There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n=15, 95% confidence interval (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n=27, 95% CI, 57.8%-87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion: This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. Methods: A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Results: Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. Conclusions: A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥6 months in patients with localized prostate cancer. Patients and Methods: A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. Results: BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) <180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). Conclusions: Neoadjuvant CAB for ≥6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To clarify which subset of stage IV prostate cancer patients benefit from combined androgen blockade (CAB) using Japanese nationwide database. Methods: A total of 3,752 patients with stage IV disease from the prospective nationwide cohort database of the Japan Study Group of Prostate Cancer (J-CaP) were enrolled. All patients started primary androgen deprivation therapy (PADT) between 2001 and 2003, and the present study was performed using the data set from December 2011. Patients were divided into two groups according to initial treatments: CAB with luteinizing hormone-releasing hormone agonist (LHRH) plus anti-androgen (AA) and non-CAB treatments such as LHRH monotherapy. The overall survival (OS) and cancer-specific survival (CSS) for each group were estimated by the Kaplan-Meier method. Results: A total of 2,967 patients (79.1 %) received CAB. Overall, no significant difference was observed in OS and CSS between the CAB group and the non-CAB group. However, CAB resulted in significantly better OS and CSS compared to non-CAB in patients with very high Japan Cancer of the Prostate Risk Assessment (J-CAPRA) scores of ten or greater ( P = 0.007 and 0.013, respectively). Multivariate analysis revealed that CAB was an independent predictive factor for better OS ( P = 0.013, hazard ratio = 0.83). Conclusions: Based on large-scale nationwide database, as PADT for prostate cancer patients with very high-risk disease, CAB resulted in better OS than other endocrine treatments. [ABSTRACT FROM AUTHOR]

Treatment of advanced prostate cancer has changed considerably in recent years, but the vast majority of advances have been made in patients with metastatic castration-resistant disease. There have been relatively fewer advances in the earlier, hormonally responsive stage of metastatic disease. Since the empiric establishment of androgen deprivation therapy as first-line therapy for metastatic prostate cancer decades ago, there have been multiple studies looking at variations of suppressing testosterone, but the overall paradigm has not been strongly challenged until more recently. In particular, the dramatic results reported by the CHAARTED trial not only bring chemotherapy to an arena historically dominated solely by hormonal therapy but also stimulate renewed efforts into improving upon our management of metastatic hormone-sensitive prostate cancer. [ABSTRACT FROM AUTHOR]

Recently two drugs, namely the antiandrogen MDV-3100 and the inhibitor of 17α-hydroxylase abiraterone have been accepted by the FDA for the treatment of castration-resistant prostate cancer (CRPC) with or without previous chemotherapy, with a prolongation of overall survival of 2.2–4.8 months. While medical (GnRH agonist) or surgical castration reduces the serum levels of testosterone by about 97%, an important concentration of testosterone and dihydrotestosterone remains in the prostate and activates the androgen receptor (AR), thus offering an explanation for the positive data obtained in CRPC. In fact, explanation of the response observed with MDV-3100 or enzalutamide in CRPC is essentially a blockade of the action or formation of intraprostatic androgens. In addition to the inhibition of the action or formation of androgens made locally by the mechanisms of intracrinology, increased AR levels and AR mutations can be involved, especially in very advanced disease. Future developments look at more efficient inhibitors of the action or formation of intraprostatic androgens and starting treatment earlier when blockade of androgens can exert long-term control and even cure prostate cancer treated at a stage before the appearance of metastases. This article is part of a Special Issue entitled ‘Essential role of DHEA’. [ABSTRACT FROM AUTHOR]

The discovery of medical castration with GnRH agonists in 1979 rapidly replaced surgical castration and high doses of estrogens for the treatment of prostate cancer. Soon afterwards, it was discovered that androgens were made locally in the prostate from the inactive precursor DHEA of adrenal origin, a mechanism called intracrinology. Taking into account these novel facts, combined androgen blockade (CAB) using a pure antiandrogen combined with castration in order to block the two sources of androgens was first published in 1982. CAB was the first treatment shown in randomized and placebo-controlled trials to prolong life in prostate cancer, even at the metastatic stage. Most importantly, the results recently obtained with the novel pure antiandrogen enzalutamide as well as with abiraterone, an inhibitor of 17ɑ-hydroxylase in castration-resistant prostate cancer, has revitalized the CAB concept. The effects of CAB observed on survival of heavily pretreated patients further demonstrates the importance of the androgens made locally in the prostate and are a strong motivation to apply CAB to efficiently block all sources of androgens earlier at start of treatment and, even better, before metastasis occurs. The future of research in this field thus seems to be centered on the development of more potent blockers of androgens formation and action in order to obtain better results at the metastatic stage and, for the localized stage, reduce the duration of treatment required to achieve complete apoptosis and control of prostate cancer proliferation before it reaches the metastatic or noncurable stage. [ABSTRACT FROM AUTHOR]

Objectives The Japan Cancer of the Prostate Risk Assessment was developed as a risk stratification instrument for patients undergoing primary androgen deprivation therapy. However, there have been no studies to validate the accuracy of the Japan Cancer of the Prostate Risk Assessment in predicting clinical outcomes. We examined whether the clinical outcomes of patients treated with combined androgen blockade could be stratified using the Japan Cancer of the Prostate Risk Assessment. Methods A total of 319 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist plus bicalutamide were included in this analysis. Progression-free survival, cause-specific survival and overall survival were compared among patients divided according to the prostate-specific antigen level at diagnosis, Gleason score on biopsy specimens, tumor-nodes-metastasis classification and Japan Cancer of the Prostate Risk Assessment score. Results The median age of the patients was 75 years, and the median prostate-specific antigen at diagnosis was 25.4 ng/mL. A total of 102 patients (32.0%) had lymph node and/or distant metastases. On univariate analysis, the factors adopted in the Japan Cancer of the Prostate Risk Assessment points were significant predictors of progression-free survival. On multivariate analysis, clinical T stage and M stage were significant predictors of progression-free survival. The probabilities of progression-free survival and cause-specific survival were significantly different among the groups categorized according to the Japan Cancer of the Prostate Risk Assessment risk strata. The probability of overall survival in the low-risk group was higher than in the other groups. Conclusions The progression-free survival, cause-specific survival and overall survival of prostate cancer patients treated by combined androgen blockade with bicalutamide were stratified by the Japan Cancer of the Prostate Risk Assessment. The Japan Cancer of the Prostate Risk Assessment score is clinically useful as a predictor of the prognosis of prostate cancer treated with combined androgen blockade. [ABSTRACT FROM AUTHOR]

Background: Primary hormonal therapy has been mostly used for patients with advanced prostate cancer, as international guidelines do not recommend its use for patients at earlier disease stages. However, there seems to be a discrepancy between the guideline recommendations and clinical practice on the use of primary androgen deprivation therapy for localized prostate cancer in Japan. Therefore, we retrospectively analyzed a single-institution experience in primary combined androgen blockade (CAB) for localized prostate cancer. Patients and methods: The study included 187 patients with T1c-T3a prostate cancer unsuitable for local definitive treatment and treated with primary CAB. Clinical outcomes, predictive factors of PSA relapse and adverse events were investigated. Results: The progression-free, disease-specific, and overall survival rates of all patients at 5 years were 63.0, 99.4 and 95.9%, respectively. Of the several parameters isolated as predictors of prostate-specific antigen (PSA) progression, nadir PSA level and the percentage of positive biopsy cores (%PBC) remained as independent prognostic factors on multivariate analysis. Toxicities were mild to moderate and well tolerated. Conclusions: Primary CAB treatment brought initial disease control without relapse in the majority of our selected cases. The %PBC may help predict time to relapse in the pretreatment setting. The results implicate that CAB can be an option as a primary treatment for clinically localized prostate cancer unsuitable for local definitive treatment. To confirm the exact efficacy of primary CAB, these findings should be reviewed in a large cohort of patients with long-term follow-up from various viewpoints, including disease control, toxicities, quality-of-life and medical cost. [ABSTRACT FROM AUTHOR]

Hormonal therapy has been the standard for advanced prostate cancer for over 60 years. Recently, the utility of androgen ablation through various means has been demonstrated for earlier stages of disease. In particular, the strongest evidence to date involves the use of hormonal therapy in combination with radiation therapy. In this article we review the basic concepts in hormonal ablation for prostate cancer and review the evidence-based studies that support the use of hormonal therapy in early stage prostate cancer. [ABSTRACT FROM PUBLISHER]

Summary: The effects of testosterone (T) and estradiol (E2) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E2 on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0±8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E2 were suppressed. In the second phase of the study, either micronized E2 1mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E2 would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E2-treated men, exhibited a trend towards improvement in their scores on both the immediate (p =.075) and delayed recall (p =.095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E2-treated men on both the immediate (p =.020) and delayed recall (p =.016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E2 failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer. [Copyright &y& Elsevier]

The article presents a randomized controlled trial that compares the survival rate from combined androgen blockade (CAB) with bicalutamide versus lutenizing hormone-releasing hormone monotherapy for advanced prostate cancer. The results of the study demonstrated significant overall survival advantage in favor of CAB. It notes that the achievement of a prostate-specific antigen (PSA) nadir was a prognostic factor for cancer survival.

We present a case report of a patient with prostate cancer who failed to demonstrate consistent testosterone suppression to castration levels and incomplete suppression of serum prostate-specific antigen, although treated with gonadotropin releasing hormone agonists for 48 months. Serum dehydroepiandrosterone, dehydroepiandrosterone sulphate, as well as the androgen metabolite, androsterone glucuronide, were elevated compared to the other patients. The present data suggest that those prostate cancer patients who have even marginally elevated adrenal androgens may especially benefit from combined androgen blockade.Prostate Cancer and Prostatic Diseases (2009) 12, 100–103; doi:10.1038/pcan.2008.15; published online 24 June 2008 [ABSTRACT FROM AUTHOR]