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The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.

ObjectivesTo compare directly survival outcomes of primary androgen-deprivation therapy (PADT) in Japan, where this treatment is endorsed by guidelines, with outcomes in the USA, where it is not.Patients and methodsData were compared between men receiving PADT in the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and the Japanese Cancer of the Prostate (J-CaP) registry database. Competing risks regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, diagnosis year, and treatment type [combined androgen blockade (CAB) vs castration monotherapy], comorbidity, and practice type.ResultsMen on PADT in J-CaP (13 880 men) were older than those in CaPSURE (1633 men), and had higher-risk disease (mean J-CAPRA score 3.8 vs 2.1, P < 0.001). They more often received CAB: 66.9% vs 46.4% (P < 0.001). Despite different risk profiles between the cohorts, CSM was similar on univariate analysis (log-rank P = 0.88). On multivariable regression, the subhazard ratio for CSM was 0.52 for J-CaP vs CaPSURE (95% confidence interval 0.40-0.68).ConclusionsMen on PADT in Japan have less than half the adjusted CSM than those in the USA. These findings support both existing guidelines endorsing PADT in Asia and discouraging its use in the West. Elucidating the reasons behind these substantial differences, which probably include both genetic and dietary/environmental factors, may help explain the varying epidemiology of prostate cancer on either side of the Pacific.

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea-Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year's meeting was hosted for the first time in Korea which has recently established its own national database-K-CaP-to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable 'template' for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the management of this condition would arise from global interactions such as this joint initiative.

This report summarizes the presentations and discussions that took place at the Sixth Joint Meeting of J-CaP and CaPSURE held in San Francisco, USA, in August 2012. The J-CaP and CaPSURE Joint Initiative was established in 2007 with the objective of analyzing, reviewing, comparing and contrasting data for prostate cancer patients from Japan and the USA within the two important large-scale, longitudinal, observational databases-J-CaP and CaPSURE. Since this initial collaboration between teams in the USA and Japan, the initiative has now expanded to include representatives of other Asian countries, several of whom have either established or are planning their own national prostate cancer databases. Several key topics were considered at this Sixth Joint Meeting including the current status of the J-CaP and CaPSURE databases and opportunities for collaboration with the more recently developed Asian prostate cancer databases. The latest comparative data from J-CaP and CaPSURE regarding outcomes following androgen deprivation therapy and combined androgen blockade were also reviewed. The possibility of a global chemoprevention trial to investigate the influence of soy isoflavones on prostate cancer incidence was considered. In addition, the ongoing debate regarding the role of screening and the use of active surveillance as a treatment option in the USA was discussed. The collaborators agreed that sharing of data and treatment practices on a global scale would undoubtedly benefit the clinical management of prostate cancer patients worldwide.

This report summarizes the presentations and discussions that took place at the Fifth Joint Meeting of J-CaP and CaPSURE held in Tokyo, Japan, in July 2011. The J-CaP and CaPSURE Joint Initiative was established in 2007 with the objective of analyzing, reviewing, comparing and contrasting data on prostate cancer patients from Japan and the USA within the two important large-scale, longitudinal, observational databases-J-CaP and CaPSURE. Since its inception, the initiative has reviewed a wide range of topics and generated valuable data on the patterns of prostate cancer treatment and patient outcomes in the two geographical regions. The objectives of this 5th Joint Meeting were to provide an update on the current status of the J-CaP and CaPSURE databases, and also to discuss perspectives from a range of other Asian countries-Japan, China, Indonesia and Korea-on the use of androgen deprivation therapy for prostate cancer. The collaborators recognize that large databases, such as J-CaP and CaPSURE, provide valuable 'real-world' information, to complement data from clinical trials, which can help to advance the clinical management of prostate cancer patients worldwide. It is anticipated that in the near future, the Joint Initiative will expand globally to include patient registries from other countries so that best practice can be shared and regional differences in patients, treatments and outcomes can be explored.

PurposeProstate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients.MethodsData were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments.ResultsJ-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA--scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage--predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84.ConclusionThe novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations.

Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M‐CaP) Study to investigate the clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi‐ethnic Asian men at real‐world setting. The M‐CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow‐up and vital status data were retrieved prospectively from the hospital‐based patients' case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression‐free survival (bPFS). The median age at diagnosis of M‐CaP patients was 70 years (interquartile range, IQR 65–75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow‐up for all patients was 23.5 months (IQR 15.9–33.6). Although 58.1% presented with late‐stage cancer, we observed ethnic and geographic disparities in late‐stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6–20.8), respectively. Late stage at presentation remains a challenge in multi‐ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to analyze the conditional survival and prognostic factors in androgen deprivation therapy for prostate cancer using the Japan Study Group of Prostate Cancer database. Methods: Data on patients treated with primary androgen deprivation therapy between 2001 and 2003 from a nationwide database of the Japan Study Group of Prostate Cancer were used. The conditional 5‐year progression‐free rate, cancer‐specific survival and overall survival, as well as the conditional mortality owing to prostate cancer and other causes were calculated as per subgroups. Prognostic factors for progression‐free rate, cancer‐specific survival and overall survival at each time after androgen deprivation therapy initiation were calculated using the Cox proportional hazards model. Results: The conditional 5‐year progression‐free rate and cancer‐specific survival, but not overall survival, gradually increased with time. The prognostic impact of stage IV characteristics (T4, N1 and M1) changed over time; however, the prognostic impact of the Gleason score remained unchanged. In the subgroup analysis, prostate‐specific mortality risk reduced over time in patients with stage IV prostate cancer, whereas non‐prostate cancer mortality increased over time in elderly patients. Conclusions: Information regarding conditional survival and mortality obtained in this study would provide a benchmark for physicians and cancer survivors. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the survival rate and to examine the risk of death from prostate cancer when accounting for competing risk of death, in men aged ≥80 y treated with primary androgen deprivation therapy (ADT). Data of patients with prostate cancer who had received ADT were extracted from a nationwide community‐based database established by the Japan Study Group for Prostate Cancer. Prognostic variables, including progression‐free survival, cancer‐specific survival, overall survival, and death rates were compared between men stratified by prostate cancer risk. Overall, 4760 patients older than 80 y were included. The proportion of low‐, intermediate‐, high‐, or very high‐risk, regional, and metastatic prostate cancer among super‐elderly men was 9.5%, 14.6%, 48.8%, 9.0%, 3.2%, and 24.9%, respectively. Survival rates decreased with increasing risk stratification. The cumulative 5‐y death rate by prostate cancer for low‐, intermediate‐, high‐, or very high‐risk, regional, and metastatic prostate cancer, was 0.92% (95% confidence interval [CI]: 0.2%‐3.6%), 1.6% (95% CI: 0.8%‐3.4%), 5.75% (95% CI: 4.25%‐7.75%), 15.6% (95% CI: 11.6%‐23.3%), 20.7% (95% CI: 13.1%‐31.7%), and 36.9% (95% CI: 32.8%‐41.4%), respectively. Our findings support that there is no need for immediate ADT for low‐ and intermediate‐risk groups. Conversely, in high‐ or very high‐risk, regional, and metastatic prostate cancer, more efforts for curative therapy and intensive therapy are needed in selected patients. [ABSTRACT FROM AUTHOR]

Objectives: To examine the differences in prognosis of prostate cancer patients receiving primary androgen deprivation therapy by region and facility type using a Japan‐wide database. Methods: Data on patients treated with primary androgen deprivation therapy between 2001 and 2003 from a nationwide community‐based database established by the Japan Study Group of Prostate Cancer were obtained. Clinicopathological characteristics and prognostic variables, including progression, cancer‐specific survival and overall survival, were compared according to region and facility type where the patients were treated. Results: Among 19 162 patients, 7102 (37.1%) and 12 060 (62.9%) men were in urban and rural areas, respectively, and 3556 (18.6%), 13 623 (71.1%) and 1983 (10.3%) patients were enrolled from academic centers, non‐academic hospitals and urological clinics, respectively. The risks of progression, cancer‐specific mortality and all‐cause mortality were comparable between urban and rural areas in propensity‐score matched analysis. Risks of progression, cancer‐specific mortality and all‐cause mortality in urological clinics were higher than those in academic centers in propensity‐score matched analysis. Conclusions: Our findings suggest that Japan facility type, but not geographical regions, might affect the prognosis of prostate cancer patients receiving primary androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association between hormone therapy and outcomes in a cohort of prostate cancer patients with a family history of prostate cancer. Methods: Data of patients with prostate cancer who had received hormone therapy were extracted from a nationwide community‐based database established by the Japan Study Group for Prostate Cancer. Family history of prostate cancer was available for 13 346 of these patients, who thus comprised the study cohort. Prognostic variables, including progression‐free survival, cancer‐specific survival and overall survival, were compared between men with familial and men with sporadic prostate cancer. Results: A positive family history was identified in 220 patients (1.6%). Patients with a positive family history were younger than those without; however, other clinicopathological characteristics and prognoses were comparable. In subgroup analysis, family history was identified as a possible favorable prognostic factor for overall survival among patients with a prostate‐specific antigen level at diagnosis <100 ng/mL and those with low or intermediate Japan Cancer of the Prostate Risk Assessment. Conclusions: Our findings show that familial prostate cancer has an early‐onset feature or is diagnosed earlier than sporadic prostate cancer. However, the prognosis of individuals with familial prostate cancer undergoing hormone therapy is comparable to those with sporadic prostate cancer. [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]

Objective: The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real‐world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017). Findings: Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration‐naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor‐targeting agents appear to be well tolerated in Asian men with metastatic castration‐resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision‐making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower‐income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side‐effect profiles of some drugs and influence prescribing. Conclusions: As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team‐based approach to treatment planning and care, delivery of best‐practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice. [ABSTRACT FROM AUTHOR]

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]

Objectives: Primary androgen deprivation therapy (PADT) had been used extensively in Japan than in the USA and European countries regardless of the disease risk or patient's age. To illustrate the consequence of PADT from daily clinical practice, we evaluated the relationship among age, disease risk, and survival of patients with prostate cancer treated by PADT in largest Asian cohort. Patients and methods: The 19,246 men subjected to PADT enrolled in the Japan Study Group of Prostate Cancer were enrolled for the present analysis. Patients were divided into four groups based on age at diagnosis: age <66, 66-70, 71-75, and >75. Risk was stratified according to the Japan Cancer of the Prostate Risk Assessment (J-CAPRA). Multivariate competing risks regression analysis was performed for OS and PFS. Results: There was downward stage migration over age. Among men aged >75 years, 34.1 % had nodal or distant metastatic disease. In contrast, 56.0 % of patients aged <66 years presented with advanced disease. The modality of hormonal therapy varied with age across risk groups; the younger age group showed a higher proportion of maximal androgen blockade, while the proportion of monotherapy use was higher in older men. The likelihood of low-risk disease by J-CAPRA classification increased significantly with increasing age ( p < 0.0001 by Pearson's chi-square test). The same as OS, the PFS rate increased with age until after the age of 75. Men aged 71-75 had better survival rates even after adjustments for treatment modality alone, or for treatment modality plus disease risk. Conclusions: Age cohorts do affect orientation toward favorable disease course after PADT with men aged 71-75 being benefiting more from PADT than other age groups. [ABSTRACT FROM AUTHOR]

Objectives To elucidate whether the disease characteristics and prognosis of stage IV prostate cancer treated with primary androgen deprivation therapy differ between young and elderly patients. Methods A total of 3006 patients identified from the database of the Japan Study Group of Prostate Cancer were included in the analysis according to the following entry criteria: age of 75 years or less and stage IV disease. These patients were stratified into three groups: young (aged ≤55 years); middle-aged (aged ≧56 and ≤65 years); and elderly (aged ≧66 and ≤75 years). Their prognoses were analyzed both within age groups and according to whether or not there was metastasis. Results The proportion of lymph node metastasis was significantly higher in the young group than in the elderly group ( P = 0.007), and there were no significant differences in other factors among age groups. The overall survival rate at 5 years in the young group was significantly worse than that in the middle-aged and elderly groups (26.6%, 59.7% and 55.3%, respectively) in patients with stage IV disease with metastasis, although there was no difference among age groups in patients with stage IV disease without metastasis. Multivariate analysis showed that younger age was an independent strong prognostic factor in stage IV disease with metastasis. Conclusions Young men with metastatic prostate cancer have a poor prognosis. Young age is an independent prognostic factor in stage IV metastatic prostate cancer patients treated with primary androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Objective In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. Methods The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. Results The 5-year overall survival in prognostic grouping- I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping -IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping -IIB was subclassified into IIB1 (except IIB2) and IIB2 ( T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping -IV was subclassified into IV1 (except IV2) and IV2 ( M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping- IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping- A (prognostic grouping- I, IIA, and IIB1), modified prognostic grouping- B (prognostic grouping- IIB2 and III), modified prognostic grouping- C (prognostic grouping- IV1) and modified prognostic grouping- D (prognostic grouping- IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Conclusion Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. [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]

The article offers information on several studies related to hormonal therapy for prostate cancer. It discusses a study in which a novel risk-assessment tool for prostate cancer called Japanese prostate cancer risk assessment was developed. In another study a deferred combined androgen blockade therapy for castration-resistant prostate cancer is discussed. A study on personalized medication of estramustine phosphate by individual single-nucleotide polymorphism analysis is also presented.

Luteinizing hormone-releasing hormone (LHRH) analogues play a pivotal role in hormonal therapy regimens for the treatment of prostate cancer. Hormonal therapy has traditionally been used as a palliative treatment for patients with advanced disease, and international treatment guidelines do not recommend its use as a first-line therapy at earlier disease stages. However, there appears to be a gap between international guideline recommendations and actual clinical practice regarding the use of primary androgen deprivation therapy (PADT) for prostate cancer therapy. Despite limited evidence to date for the impact on clinical outcomes, the use of PADT in patients with localized or locally advanced prostate cancer has increased in many countries, most notably Japan. Clinical evidence is now accumulating to confirm the valuable role of PADT, both as monotherapy but particularly when used as part of a maximal androgen blockade regimen, on the long-term control of both localized and locally advanced disease, and importantly on survival outcomes in these patients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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.

To assess quality of life (QOL) data from a double-blind Phase III study evaluating bicalutamide (Casodex™) 80 mg as part of maximum androgen blockade (MAB) in patients with previously untreated advanced prostate cancer. Patients with untreated stage C/D prostate cancer were randomized to MAB with bicalutamide plus a luteinizing hormone-releasing hormone agonist (LHRHa) or LHRHa monotherapy. QOL was evaluated at baseline and at weeks 1, 5, and 24 using the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. A total of 203 patients were assessed for QOL. The MAB group had more rapid and greater improvements in “emotional well-being” and “prostate cancer-specific issues” domain scores than the monotherapy group. Further analysis of “prostate cancer-specific issues” revealed that, compared with monotherapy, MAB provided a greater improvement in “micturition disorder”-related QOL. Complete improvement rates for items related to “pain and micturition disorder” were also higher with MAB. Item scores of “pain and micturition disorder” did not correlate strongly with prostate-specific antigen levels or tumor size. Fewer patients who had deterioration in their “pain and micturition disorder” item scores at week 1 in the MAB group than the monotherapy group. Maximum androgen blockade with bicalutamide plus LHRHa did not reduce the overall QOL of patients with previously untreated advanced prostate cancer. MAB was superior to monotherapy in achieving early improvement of QOL related to micturition disorder and pain. [ABSTRACT FROM AUTHOR]

The exposure rate of screening for prostate cancer using prostate-specific antigen (PSA) in Japan is still very low compared with that in the USA or Western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8 times higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death. [ABSTRACT FROM AUTHOR]

The old concept of androgen depletion therapy (ADT) for prostate cancer, which had been established on the basis of clinical experiences essentially on the far advanced disease, should be changed. The recent major increase in the diagnosis of localized and locally advanced prostate cancer due to prostate-specific antigen (PSA) screening prompts us to make clear the role of ADT for such an early stage of prostate cancer. Recent literature has proved that combination therapy of castration (medical or surgical) and non-steroidal anti-androgens (maximal androgen blockade, MAB, or combined androgen blockade, CAB) is markedly effective on non-metastatic prostate cancer. It is important to promote basic and clinical research based on the understanding that cure of prostate cancer is almost always possible with ADT if progression to the hormone-independent prostate cancer which accompanies metastatic disease can be avoided. [Copyright &y& Elsevier]

The article summarizes the Clinical Practice Guidelines for Prostate Cancer (GL) created by the Japanese Urological Association. Its practice guidelines have been defined as systematicaly developed statements concerning appropriate insurance-registered healthcare modalities for specific illness that can help the treating doctor and the patient making a medical decision. Moreover, the present guidelines do not reflect the actual status of prostate cancer in Japanese patients.

We examined associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men. Two hundred patients and 200 age-matched controls (+/-5 y) were selected from 3 geographic areas of Japan. BMI, physical activity, occupation, family history of prostate cancer, and medical history were not associated with prostate cancer risk. Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category (> or = 89.9 mg/d) compared with the lowest category (<30.5 mg/d) of isoflavone intake was 0.42 (95% CI = 0.24-0.72) and the linear trend was significant (P < 0.01). PUFA, (n-6) fatty acids, and magnesium were significantly associated with decreased risk but not after adjustment for isoflavone intake. Isoflavone intake was correlated with the intake of PUFA (r = 0.68, P < 0.001), (n-6) fatty acids (r = 0.69, P < 0.001), and magnesium (r = 0.56, P < 0.001), because soy products contain high levels of these nutrients. On the other hand, isoflavone significantly decreased the risk of prostate cancer regardless of adjustment by PUFA, (n-6) fatty acids or magnesium. In conclusion, our findings indicate that isoflavones might be an effective dietary protective factor against prostate cancer in Japanese men. [ABSTRACT FROM AUTHOR]

Data from the Japanese Urological Society showed that, in Japan, almost half of patients with localized prostate cancer are treated with hormone therapy (HT), regardless of disease stage, and that radiation therapy (RT) is also widely used to treat high-risk patients. A retrospective study was undertaken in Japan to evaluate the potential benefits of using primary HT in locally advanced prostate cancer. Of 628 patients in the study, 63.5% were treated with combined androgen blockade (CAB; luteinizing hormone-releasing hormone agonists plus an antiandrogen) and 36.5% with medical or surgical castration. CAB treatment was significantly better than hormone monotherapy for disease-specific survival. The results also showed that, even if a patient is classified as ‘high-risk’, a good prognosis could normally be predicted based on certain variables: if their initial prostate-specific antigen (PSA) level was ≤ 20 ng/mL, their Gleason score was ≤ 6, and their nadir PSA decreased to ≤ 0.2 ng/mL within 6 months of HT. In this subgroup of ‘good responders’, any treatment, be it prostatectomy, RT or CAB, is likely to be effective. However, in ‘poor responders’, combined therapies with CAB and high-dose rate brachytherapy are likely to be needed for a clinical response. While HT is effective, it might be associated with a reduction in the patient’s quality of life (QoL) due to adverse effects, e.g. a reduction in sexual function. Results from the analysis of QoL questionnaires completed by men of different ages with prostate cancer found that only sexual function, and not other QoL variables, in men aged 50–59 years appeared to be reduced in men who had HT, compared to age-matched controls. [ABSTRACT FROM AUTHOR]

Background: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer. Methods: A total of 29 patients with untreated, histologically proven prostate cancer were examined using an elastographic imaging technique. The patient was scanned in the dorsosacral position and the prostate was manually compressed with a transrectal ultrasonic probe. The echo signals from inside the tissue were measured before and after the tissue compression and an elastogram was generated by spatially differentiation of the displacement distribution. Results: Elastography depicted the cancer lesion as a harder tissue than the surrounding normal prostatic tissue. Elastography successfully detected 93% (27 patients) of the untreated prostate cancer lesions. Detection of cancer lesions using elastography was significantly higher than by digital rectal examination (59%; 17 patients) and transrectal ultrasonography (55%; 16 patients). Conclusion: Elastography has great potential as a useful modality for diagnosis of prostate cancer. Differentiation between cancerous and normal tissues can be expected to become more accurate as a result of technical advances in the quantification of tissue hardness. [ABSTRACT FROM AUTHOR]

Aim: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. Methods: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. Results: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level ≤20 ng/mL, Gleason score ≤7, and time to nadir PSA ≤6 months) accounted for approximately one-third of the total number of T1c–T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. Conclusions: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy. PATIENTS AND METHODS Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2. RESULTS The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival. CONCLUSIONS The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population. [ABSTRACT FROM AUTHOR]

Purpose: We determined the chemopreventive effect of the antiandrogen bicalutamide (Zeneca Co., Ltd., Osaka, Japan) on Fisher 344 rat prostate carcinogenesis induced by DMAB (3,2′-dimethyl-4-aminobiphenyl) (Nard Co., Ltd., Osaka, Japan). We have previously reported that rat prostate microscopic carcinogenesis in this model was paradoxically enhanced when continuous treatment with bicalutamide was begun 20 weeks after the initiation of DMAB. In the current study we determined whether antiandrogen would promote or suppress the prostate carcinogenesis when administration was begun at a later period of carcinogenesis. Materials and Methods: DMAB at a dose of 50 mg/kg was injected subcutaneously into all animals 10 times at 2-week intervals. To clarify the target lesions of bicalutamide we used 2 control groups (groups 1 and 2). Animals in groups 1 and 2 were autopsied at 60 and 74 weeks, respectively, after the initiation of DMAB. Treatment with bicalutamide began in the 60th week in group 3 rats and continued for 14 weeks. They were sacrificed in the 74th week. Results: Microscopic cancer was revealed in 27% of group 1 rats and the incidence was increased to 42% in group 2 (statistically not significant). Delayed bicalutamide treatment significantly suppressed the cancer lesion. No cancerous lesion was detected in the ventral or other lobes of the prostate of the rats in group 3. In contrast, bicalutamide did not affect the incidence of PIN. The difference in the incidence of PIN in groups 2 and 3 (84% and 78%, respectively) was not significant. Conclusions: The current investigation indicates that, if bicalutamide is started in the later period, it can efficiently eradicate existing microscopic cancer. Despite this suppressive effect on microscopic cancer bicalutamide permits the persistence of PIN. The latter finding suggests that the sensitivity of PIN to antiandrogen might be more complicated than previously recognized. [Copyright &y& Elsevier]

Background: The effects of preoperative androgen deprivation on the outcomes of prostate cancer patients who received radical prostatectomy and subsequent adjuvant endocrine therapy have not yet been fully evaluated. Methods: Patients with stage A2, B or C prostate cancers were randomized to one of two groups: group I (n = 90), who received androgen deprivation (leuprolide and chlormadinone acetate) for 3 months followed by radical prostatectomy and subsequent adjuvant endocrine therapy (leuprolide alone), and group II (n = 86), who underwent the surgery followed by 3-month androgen deprivation (leuprolide and chlormadinone acetate) and subsequent adjuvant endocrine therapy (leuprolide alone). The effects of preoperative androgen deprivation on survival, clinical relapse (serum prostate specific antigen, PSA, above the normal level, local recurrence, or distant metastases), and PSA relapse (PSA above the detectable level) were evaluated at 5 years or later after treatment. Results: There were no significant differences in overall, cause-specific, clinical relapse-free, or PSA relapse-free survival rates between the two groups. In a subanalysis, no prostate cancer deaths or clinical relapses were noted in 29 patients with organ-confined disease (OCD: negativity of capsular invasion, seminal vesicle invasion, surgical margins or nodal involvement). The odds ratio for OCD depending on group assignment was 2.44 (95% confidence interval, CI 1.04-5.72), for group I, demonstrating a higher probability of having OCD. This ratio was increased to 4.00 (95% CI 1.06- 15.16) if the analysis was conducted in a subpopulation with prostate specific antigen levels less than 35.6 ng/mL and with clinical stage B or C cancers. Conclusion: Preoperative androgen deprivation has no demonstrable benefit in 5-year outcomes for patients undergoing radical prostatectomy and adjuvant endocrine therapy. However, it did increase the probability of OCD, which was associated with no clinical relapse during the follow-up. A longer observation is needed to clarify the exact extent of the benefits in terms of survival. [ABSTRACT FROM AUTHOR]

We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 ( n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 ( n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 ( n = 29, 16%) than study 2 ( n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes. [ABSTRACT FROM AUTHOR]

Background: The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer. Methods: Stage A2, B or C prostate cancers were randomized to one of two groups: (i) group I (n = 90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II (n = 86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA) > 1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA > 0.2 ng/mL) were evaluated at 2 years after randomization. Results: There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it (P < 0.1). Conclusions: Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life. [ABSTRACT FROM AUTHOR]

Stage C prostate cancer, where the tumour has extended beyond the capsule of the prostate, is typically a high-risk disease. According to the National Cancer Institute Physician Data Query the treatments of choice for stage C disease comprise external beam radiation therapy (with or without the addition of adjuvant hormone therapy), androgen deprivation by either surgery or hormone therapy, radical prostatectomy, or careful observation. From 2001, the Japanese Urological Association initiated computer-based registration of all patients with prostate cancer in Japan. Data show that overall, 57% of all patients and 46% of those with T1c to T3 disease had primary androgen deprivation therapy (PADT). Similarly, the Japanese Prostate Cancer Group undertook a large-scale epidemiological surveillance study in Japan and found that the most commonly used hormone therapy is PADT, regardless of disease stage. To date, two randomized, controlled trials of the effect of PADT on stage C prostate cancer in elderly (≥75 years old) patients have been undertaken in Japan. The results showed that patients with locally advanced prostate cancer treated with PADT are likely to have a life-expectancy similar to that of the normal population. In one study, combined androgen blockade (CAB) with leuprorelin plus chlormadinone appeared to prolong time to disease progression when compared with leuprorelin monotherapy, but there was no difference in survival between these treatment groups. In a second study CAB with an luteinizing hormone-releasing hormone (LHRH) agonist plus bicalutamide was found to prolong time to progression when compared with LHRH agonist monotherapy, but survival results for these regimens are still awaited. [ABSTRACT FROM AUTHOR]