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This fourth edition of the Japanese Clinical Practice Guidelines for Prostate Cancer 2023 is compiled. It was revised under the leadership of the Japanese Urological Association, with members selected from multiple academic societies and related organizations (Japan Radiological Society, Japanese Society for Radiation Oncology, the Department of EBM and guidelines, Japan Council for Quality Health Care (Minds), Japanese Society of Pathology, and the patient group (NPO Prostate Cancer Patients Association)), in accordance with the Minds Manual for Guideline Development (2020 ver. 3.0). The most important feature of this revision is the adoption of systematic reviews (SRs) in determining recommendations for 14 clinical questions (CQs). Qualitative SRs for these questions were conducted, and the final recommendations were made based on the results through the votes of 24 members of the guideline development group. Five algorithms based on these results were also created. Contents not covered by the SRs, which are considered textbook material, have been described in the general statement. In the general statement, a literature search for 14 areas was conducted; then, based on the general statement and CQs of the Japanese Clinical Practice Guidelines for Prostate Cancer 2016, the findings revealed after the 2016 guidelines were mainly described. This article provides an overview of these guidelines. [ABSTRACT FROM AUTHOR]

Aim: We aimed to determine Japanese metastatic castration resistant prostate cancer (CRPC) patients' Ra-223 treatment experience. Patients & methods: Patients answered the Cancer Therapy Satisfaction Questionnaire (CTSQ domains: Satisfaction with Therapy [SWT], Expectations of Therapy [ET], Feelings about Side Effects [FSE]), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the FACT-Bone Pain (FACT-BP) Questionnaire at baseline, during (vists 3 and 5) and after treatment (end of observation; EOO). Results: Data from 72 patients were included. Baseline median CTSQ scores SWT: 66.1 (IQR19.7), ET: 75.0 (IQR45), and FSE 68.8 (IQR 34.4) were unchanged during vists 3 and 5, but the SWT (-3.57 [IQR17.9]) and ET (-5.0 [IQR30]) decreased while FSE was unchanged (0.0 [IQR31.25]) at EOO. The median MAX-PC (18.0 [IQR 49]) score was unchanged (0.0, IQR 6) while the median FACT BP (54.0 [IQR13]) score decreased by -1.0 (IQR 8) at EOO. Conclusion: Japanese metastatic castration resistant prostate cancer patients' experience is stable during Ra-223 treatment. We wanted to know the treatment experience with Radium-223 (Ra-223) among Japanese prostate cancer patients. Ra-223 is a radioactive molecule used for the treatment of metastatic castration resistant prostate cancer. We asked patients to answer different questionnaires on treatment satisfaction, anxiety and quality of life before, during, and after treatment with Ra-223. Based on the patients' answers to our questionnaires, treatment satisfaction, anxiety and quality of life remain stable while the patients undergo treatment with Ra-223, but in some aspects may decline after treatment. The results mean that patients' experience during Ra-223 treatment is stable but patients should share any concerns they have about their treatment with their doctors. A study on Japanese metastatic castration resistant prostate cancer patients who receive Radium-223 therapy showed that treatment satisfaction, anxiety and health-related quality of life remain stable among patients while undergoing Ra-223 treatment. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of high‐risk metastatic hormone‐naïve prostate cancer is poor, and real‐world evidence of therapeutic options and sequences is lacking. The J‐ROCK study aimed to evaluate the outcomes in a real‐world setting in Japan. Methods: Patients with high‐risk metastatic hormone‐naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). Results: In this first interim analysis (cut‐off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow‐up period was 7.6 (range 0.1–20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate‐specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate‐specific antigen‐progression‐free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345–1.147]). Conclusions: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real‐world treatment of high‐risk metastatic hormone‐naïve prostate cancer in Japan. Some factors including prostate‐specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate‐specific antigen‐progression‐free survival in patients with high‐risk metastatic hormone‐naïve prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: The TITAN study is a randomized, double‐blind, placebo‐controlled, multinational trial that evaluated apalutamide with androgen deprivation therapy in patients with metastatic castration‐sensitive prostate cancer. At the first interim analysis in the Japanese subpopulation (median follow‐up 25.7 months), there was an improvement in overall survival and radiological progression‐free survival with apalutamide versus placebo. Here, we report the final analysis results for the Japanese subpopulation. Methods: Patients were randomized 1:1 to receive apalutamide 240 mg or placebo. After the first interim analysis, protocol treatment was unblinded, and crossover was allowed. Efficacy and safety were evaluated in the preplanned, event‐driven final analysis. Results: Fifty‐one patients were Japanese (apalutamide n = 28; placebo n = 23). After a median follow‐up of 46.0 months, the median overall survival was not reached neither in the apalutamide nor the placebo group; the hazard ratio was 0.45, favoring apalutamide, which was consistent with the overall population. Hazard ratios for time to cytotoxic chemotherapy (0.39), time to pain progression (0.87), and time to chronic opioid use (0.82) also favored apalutamide and were comparable with those of the overall population. Time to prostate‐specific antigen progression and progression‐free survival 2, respectively, was favored in the apalutamide group (0.21 and 0.44). Apalutamide was associated with higher incidences of rash and fracture in the Japanese subpopulation compared with the overall population. Conclusions: The efficacy of apalutamide with androgen deprivation therapy in Japanese patients was consistent with efficacy demonstrated in the overall population. No new safety concerns emerged with long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone‐sensitive prostate cancer. Methods: A post‐hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone‐sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end‐point was radiographic progression‐free survival. Secondary end‐points included time to prostate‐specific antigen progression and overall survival. Results: Of 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end‐points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3–4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population. Conclusions: Enzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone‐sensitive prostate cancer, consistent with the overall population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration‐sensitive prostate cancer from the phase 3, randomized, global TITAN study. Methods: Men with metastatic castration‐sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression‐free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal‐related events. Safety was also assessed. Results: Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression‐free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205–2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210–3.361; P = 0.805). In the interim analysis, the median radiographic progression‐free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. Conclusions: The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration‐sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients. [ABSTRACT FROM AUTHOR]

Objectives: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. Methods: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. Results: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan–Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. Conclusion: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP. [ABSTRACT FROM AUTHOR]

This open‐label, phase I dose‐finding study evaluated the gonadotropin‐releasing hormone antagonist, TAK‐385, in Japanese patients with nonmetastatic prostate cancer. In a two‐part design, patients received daily oral TAK‐385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose‐escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose‐limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate‐specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose‐limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK‐385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady‐state Tmax was ~1‐2 hours and mean t1/2z was 67‐79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate‐specific antigen of >90% from baseline were observed through 96 weeks. TAK‐385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. ClinicalTrials.gov: NCT02141659. [ABSTRACT FROM AUTHOR]

Background: Automated bone scan index (aBSI) change (ΔBSI) after treatment and survival in men with prostate cancer remains unclear. We evaluated the correlation between ΔBSI after cabazitaxel and overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (CRPC). Methods: We retrospectively enrolled 32 men with bone metastatic CRPC who had received cabazitaxel. The correlation between ΔBSI from baseline to 16 weeks after starting cabazitaxel and OS was analyzed by multivariate analysis. Results: Median age and time to CRPC were 70.7 years and 9.5 months, respectively. The median cycles of docetaxel before cabazitaxel were eight. Ten (31.2%) patients had visceral metastases at baseline. Median baseline prostate-specific antigen (PSA) was 123.0 ng/mL. The median aBSIs at baseline and 16 weeks after cabazitaxel were 3.2 and 4.4%, respectively. Improvements in aBSI and PSA after 16 weeks of cabazitaxel occurred in 7 (21.9%) and 12 patients (37.5%), respectively. There were no correlations between ΔBSI and OS (p = 0.55), but PSA change was significantly correlated with OS (p = 0.03) by multivariate analysis. Conclusions: This study demonstrated that ΔBSI from baseline to16 weeks after starting cabazitaxel was not correlated with OS among men with bone metastatic CRPC. Further prospective studies may be warranted to confirm the limited utility of aBSI in this setting. [ABSTRACT FROM AUTHOR]

Boyd et al. reported that only 8.7% of localized PC patients were informed about the possibility of future male-infertility before PC treatment.[2] Most PC patients are relatively aged and most physician tend to avoid about discussing it with their patients. Abbreviations & Acronyms PC prostate cancer YCUMC Yokohama City University Medical Center TESE testicular sperm extraction Male-fertility preservation - sperm cryopreservation is a gold standard for male-fertility preservation - has been paid attention for cancer patients over the past two decades because significant cancer treatment increasing cancer survivors and leading demand for future parenthood.[1] Unfortunately, prostate cancer (PC) patients are not adequately informed about treatment-induced infertility before PC treatment although there were certain patients who hope fertility preservation.[2] In this study, we report real-world data about sperm cryopreservation before definitive therapy for early-stage PC at our institution. Therefore, physician should inform about possibility of male-infertility due to PC treatment and discuss about sperm cryopreservation before PC treatment with patients who hope male-fertility preservation. [Extracted from the article]

Non‐inferiority in the cumulative castration rate of the 3‐month formulation of degarelix compared with the 3‐month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open‐label, parallel‐arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non‐inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end‐point was the cumulative castration rate from day 28 to day 364 and the non‐inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non‐inferiority of the 3‐month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate‐specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non‐inferiority of the 3‐month formulation of degarelix to goserelin was shown for testosterone suppression. The 3‐month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170). [ABSTRACT FROM AUTHOR]

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is,29%of Japanese physicians underestimated patients’ preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated bone scan index (BSI) as a predictive biomarker for time to castration-resistant prostate cancer (CRPC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: We identified 85 consecutive mHSPC patients treated with first-line androgen deprivation therapy. We analyzed the correlations between time to CRPC and clinicopathological characteristics, including age, prostate-specific antigen (PSA) level, Gleason score, clinical TNM stage, hemoglobin, lactate dehydrogenase, C-reactive protein, and BSI. Results: The median BSI was 2.7%. Progression to CRPC occurred in 55 (64.7%) patients and the median time to CRPC was 12.9 months. In multivariate analysis, 3 significant risk factors for time to CRPC were identified: age (>73 vs. ≤73 years; hazard ratio [HR] 0.53), p = 0.038, PSA level (>270 vs. ≤270 ng/mL; HR 0.53, p = 0.038), and BSI (>2.7 vs. ≤2.7%; HR 2.97, p < 0.001). Conclusion: Age, PSA level, and BSI were found to be significant predictive factors for time to CRPC in patients with mHSPC. [ABSTRACT FROM AUTHOR]

Objective:More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [–2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. Materials and methods:The subjects were 50 consecutive men with a PSA level of 2.0–10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. Results:In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). Conclusion:PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer. [ABSTRACT FROM AUTHOR]

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is, 29% of Japanese physicians underestimated patients' preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States. [ABSTRACT FROM AUTHOR]

Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-yearold male was referred to our hospital for the further examination of an elevated prostatespecific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate. [ABSTRACT FROM AUTHOR]

Background: In most cases, prostate cancer metastasizes to the lymph nodes, bone, and liver. In very rare cases, it metastasizes to the ureter. Due to the difficulty in making a preoperative diagnosis, ureteral metastasis from prostate cancer is typically diagnosed after nephroureterectomy.Case Presentation: A 77-year-old Asian Japanese man with right hydronephrosis and hydroureter was referred to our hospital to undergo further examination due to the suspicion of ureteral cancer. He had been diagnosed 2 years previously with prostate cancer with a Gleason score of 4+5=9. He received radiotherapy and androgen deprivation therapy. A nephroureterectomy was performed for suspected right ureteral cancer. On the basis of a histopathological examination, poorly differentiated adenocarcinoma was suspected, and the tumor cells were positive for prostate-specific antigen immunohistochemically.Conclusions: We herein report a rare case of ureteral metastasis in castration resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common disease in elderly Japanese men.1,2 A geriatric assessment is therefore required for prostate cancer patients. At our institution, we assessed the G8 score for 76 localized prostate cancer patients, and the mean score was 15.2 for patients who underwent radical prostatectomy, 14.1 for those who underwent radiotherapy and 13.6 for those who underwent androgen deprivation therapy. In that study, the mean G8 score for localized prostate cancer was 14.5, the G8 score for those who underwent robot-assisted radical prostatectomy was 15.0, radiotherapy was 14.0 and androgen deprivation therapy was 12.0. [Extracted from the article]

To address concerns regarding increased risk of prostate cancer (PrCA) among angiotensin receptor blocker (ARB) users, we used national retrospective data from the Department of Veterans Affairs (VA) through the Veterans Affairs Informatics and Computing Infrastructure. We identified a total of 543,824 unique Veterans who were classified into either ARB treated or not-treated in 1:15 ratio. The two groups were balanced using inverse probability of treatment weights. A double-robust cox-proportional hazards model was used to estimate the hazard ratio for PrCA incidence. To evaluate for a potential Gleason score stage migration, we conducted weighted Cochrane-Armitage test. Post weighting, the rates of PrCA in treated and not-treated groups were 506 (1.5%) and 8,269 (1.6%), respectively; representing a hazard ratio of (0.91, p-value .049). There was no significant difference in Gleason scores between the two groups. We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation (as indicated by Gleason score). Findings from this study support Food and Drug Administration's recent conclusion that ARB use does not increase risk of incident PrCA. [ABSTRACT FROM AUTHOR]

Purpose: For patients with metastatic castration-resistant prostatic cancer (mCRPC), docetaxel plus prednisone leads to superior survival and a higher response rate compared with mitoxantrone plus prednisone. We analyzed the efficacy of long-term treatment with ≥10 cycles of docetaxel, and validated the risk group classification in predicting overall survival (OS) in Japanese patients with mCRPC. Patients and Methods: Fifty-two patients with mCRPC were administered 55 mg/m² docetaxel and 8 mg dexamethasone, every 3 or 4 weeks, simultaneously with hormonal therapy and daily oral dexamethasone. They were divided into two groups, short-term (9 or fewer cycles) and long-term (10 or more cycles). Four risk factors including the presence of anemia, bone metastases, significant pain and visceral metastases were utilized for the risk group classification. Results: Fourteen patients (27%) had an elevation of PSA in spite of docetaxel treatment, while 23 patients (44%) had a decline in PSA level, including 9 patients (17%) whose PSA level declined by ≥50%. The median duration of OS after the initiation of this therapy was 11.2 months in the short-term group and 28.5 months in the long-term group. The good risk group showed a significant difference in OS compared with the intermediate and poor risk groups (P<0.001). The median number of cycles of treatment was 14, 4 and 3 for each risk group, respectively (p<0.01). Conclusions: The present study indicated that ≥10 cycles of this docetaxel therapy can significantly prolong survival in Japanese men with CRPC. This risk group classification for men with mCRPC at the initiation of this chemotherapy is useful. [ABSTRACT FROM AUTHOR]

OBJECTIVES: • To perform transrectal ultrasonography (TRUS) with an ultrasonography (US) contrast agent to visualize prostate cancer. • To explore the possibility of targeted biopsy by studying the findings obtained by different cancerous tissue imaging modalities and evaluating needle biopsies from prostate cancer using contrastenhanced ultrasonography (CEUS). PATIENTS AND METHODS: • In all, 41 patients undergoing prostate biopsy and 13 patients undergoing prostatectomy received i.v. injection of the US contrast agent (Sonazoid®). • We evaluated pre-contrast and contrastenhanced US images, and then compared ultrasonographic images and the pathological findings. RESULTS: • Cancer was significantly more frequent at the sites of targeted biopsy where CEUS findings suggested cancer (36.3%) than at sites of systematic biopsy (17.7%, odds ratio = 2.7, P = 0.0026). • In cases with prostate-specific antigen (PSA) level < 10 ng/mL, in particular, prostate cancer was detected at a significantly higher rate by targeted biopsy than by systematic biopsy (27.3 vs 9.5%, odds ratio = 3.4, P = 0.013). • Pathological examination found 26 tumours in prostatectomy specimens. The diameters of the 10 CEUS-identified tumours were significantly greater than those of the 16 lesions missed by US (mean 18.7 vs 5.9 mm). • CEUS findings suggestive of cancer varied widely: strong contrast enhancement, rapid contrast enhancement, vessels with abnormal perfusion and low contrast enhancement. CONCLUSIONS: • CEUS could be useful for targeted biopsy in patients with a PSA level < 10 ng/mL. • The CEUS findings suggestive of prostate cancer are more varied than previously reported. • Detailed examination of CEUS images and application of the data to prostate biopsy could lead to more efficient diagnosis. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce expression of NSAID-activated gene 1 (NAG-1). NAG-1 expression in prostate cancer has previously been detected by microarray and immunohistochemical analyses. We examined the mRNA expression of NAG-1 by quantitative real-time polymerase chain reaction using 51 human prostate cancer tissue specimens. The level of NAG-1 expression was higher in prostate cancer than in normal prostate tissues (p = 0.025). The level of NAG-1 expression was also significantly higher in well-differentiated prostate cancer than in moderately (p = 0.04) and poorly differentiated adenocarcinomas (p = 0.03). These data suggest that NAG-1 may be a new biomarker for evaluating the grade of malignancy in prostate cancer. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether the 2005 International Society of Urologic Pathology (ISUP) Gleason Grading Consensus is clinically more useful than the conventional Gleason score (CGS), we compared the CGS and ISUP GS (IGS) of prostate needle biopsy (NB) and radical prostatectomy (RP) specimens, and evaluated the prognostic value of the ISUP GS. PATIENTS AND METHODS Of 250 patients undergoing RP, 103 with clinical stage T1–2 N0M0 were enrolled. Pathological tumour grades of NB and RP specimens were classified according to CGS by experienced pathologists in the central pathology department of our hospital, and retrospectively according to IGS by one uropathologist at the central pathology department of another hospital. All patients had RP with no neoadjuvant or adjuvant therapy. We analysed associations of CGS and IGS with biochemical recurrence-free survival (BRFS) after RP. RESULTS The concordance rates between NB and RP specimens by CGS and IGS were 64.1% and 69.9%. Under-grading and over-grading rates by CGS and IGS were 28.2% and 7.8% for NB, and 27.2% and 2.9% for RP, respectively. There was a significant difference in the over-grading rate between CGS and IGS ( P = 0.026). When CGS and IGS of NB and RP specimens were compared, the concordance rates were similar, at 67% and 69.9%. The IGS was higher, by 15.6% in NB and by 20.4% in RP specimens, than CGS. Patients were divided into three groups based on IGS of NB specimens (≤6, 7 and ≥8). These groups differed significantly in BRFS after RP ( P = 0.022); CGS showed no such association. CONCLUSIONS The IGS of NB specimens were significantly associated with BRFS after RP. The ISUP system is thus clinically useful for determining the most appropriate treatments for patients with early-stage prostate cancer. [ABSTRACT FROM AUTHOR]

Background: In the present study, we compared 12- with 8-core biopsy in patients with prostate-specific antigen (PSA) levels of 4.0–20.0 ng/ml. We also examined whether the free/total (F/T) PSA ratio is useful for cancer detection in 12-core biopsy. Methods: A total of 419 men with PSA level between 4.0 and 20.0 ng/ml underwent transrectal ultrasound-guided transperineal needle biopsies of the prostate. Of these men, 235 underwent 8-core biopsy and 184 underwent 12-core biopsy. We compared the cancer detection rate between the 8- and 12-core biopsy groups by analyzing the PSA value, and especially the F/T PSA ratio. Results: The cancer detection rate in the 12-core group (35.9%) was significantly higher than in the 8-core group (23.8%). In cases of PSA level of 4.0–20.0 ng/ml with F/T PSA ratio less than 0.11, the cancer detection rate was 53.1% in the 12-core biopsy group. Performing 12-core biopsy resulted in a marked difference of cancer detection rate between men with F/T PSA ratio less than 0.11 and those with more than 0.12 in gray zone PSA (48.2% and 17.5%, respectively). Conclusions: Twelve-core biopsy can achieve a higher detection rate of prostate cancer than 8-core biopsy using F/T PSA ratio. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the antitumour effect of electroporation (EP), a drug delivery system that has been shown to be effective synergistically with antitumour drugs, with bleomycin on the growth of prostate cancer xenografts in nude mice. MATERIALS AND METHODS PC-3 cells were implanted subcutaneously into nude mice. After determination of the optimal conditions of electric pulse voltage and bleomycin dose, tumour growth in mice treated with EP plus bleomycin was compared with that in mice receiving EP alone, bleomycin alone or no treatment. In all four groups, apoptosis in the tumours was assessed. RESULTS There was a significant reduction in tumour growth in mice that received EP with bleomycin. Apoptotic cells in tumours at 24 h after treatment with EP plus bleomycin showed a significant difference compared with the other three groups, but not at 12 h after treatment. CONCLUSIONS These results indicate the possibility that EP with bleomycin could be effective as an ablation therapy for prostate cancer, especially androgen-independent cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prostate and seminal vesicle motion in patients during both simulation and radiotherapy by rectal gas removal. Methods and Materials: A total of 34 patients were treated in a whole pelvic radiotherapy (WPRT) arm and 42 patients in a non-WPRT arm. Of the 76 patients, 42 (26 in the non-WPRT arm and 16 in the WPRT arm) were instructed to insert their index finger and wash their rectums to evacuate their rectal gas. In addition to the planning computed tomography scan, three subsequent computed tomography scans were obtained during RT. The organs were outlined on each computed tomography image. Changes in the position of the prostate and seminal vesicles were analyzed using the center of mass (COM) coordinate system. The time trend, overall variations, systematic variations, and random variations were analyzed. Results: The average cross-sectional area in the rectal gas removal group was significantly smaller than in all patients and in the WPRT arm. The vector of the prostate and seminal vesicle displacement for the rectal gas removal group was significantly smaller than in all patients. With rectal gas removal, the 95% confidence limit of the prostate displacement vector was reduced by 2.3 mm in the non-WPRT arm and 2.9 mm in the WPRT arm. The 95% confidence limit of the seminal vesicle displacement vector was reduced by 0.3 mm in the non-WPRT arm and 4.4 mm in the WPRT arm. Conclusions: Using rectal gas removal, the cross-sectional area could be decreased, resulting in reduced motion and margins for the prostate and seminal vesicles. This is especially important for WPRT patients who require RT to the prostate, seminal vesicles, and pelvic lymph nodes. [Copyright &y& Elsevier]

Although a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms have not been elucidated. It is known that angiotensin-II (Ang-II) plays a fundamental role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang-II type-1 (AT1) receptor in cardiovascular cells. Interestingly, there is increasing evidence that the renin-angiotensin system (RAS) is implicated in the development of various cancers. As we previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review provides an insight into the key role of Ang-II and the AT1 receptor, and the possibility of ARBs for molecular targeting of mitogenesis and angiogenesis in prostate cancer. [ABSTRACT FROM AUTHOR]

Background. We previously demonstrated that an angiotensin II receptor blocker (ARB) had the potential to inhibit cell proliferation of prostate cancer. In this study, we examined whether an ARB could elicit an antiproliferative effect on hormone-refractory prostate cancer, clinically. Methods. Twenty-three patients with advanced hormonerefractory prostate cancer who had already received secondary hormonal therapy using dexamethasone, and who were no longer receiving conventional therapy, were enrolled. All of the patients received candesartan 8mg once daily per os and, simultaneously, androgen ablation. Change in prostate-specific antigen (PSA) was determined as the primary endpoint. The secondary end-point was change in performance status (PS). To investigate angiotensin II type 1 (AT1) receptor expression in prostate cancer tissue, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed, using specimens, from untreated patients with prostate cancer. Results. Eight patients (34.8%) showed responsive PSA changes; six showed a decrease immediately after starting administration and two showed a stable level of PSA. Six men with a PSA decline of more than 50% showed an improvement in PS. The mean time to PSA progression (TTPP) in responders was 8.3 months (range, 1-24 months). Half of the patients showed stable or improved PS during treatment. With regard to toxic effects, only one patient showed hypotension during treatment. The RT-PCR showed that AT1 receptor expression in well-differentiated adenocarcinoma was higher than that in poorly differentiated adenocarcinoma. Conclusion. These data showed that an ARB had potential biological effects on prostate cancer, suggesting the usefulness of the cytostatic activity of such agents on recurrent prostate cancer. [ABSTRACT FROM AUTHOR]

Background: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. Methods: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1–3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. Results: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group ( P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels ≥0.01 ng/mL showed biochemical failure. Conclusion: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy. [ABSTRACT FROM AUTHOR]