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Background: We previously conducted a retrospective Japanese cohort study of patients who underwent radical prostatectomy (RP) between January 2010 and December 2020 in Ehime Prefecture. This study revealed an increase in the number of RP, but other treatment trends remained unclear. In the current study, we examined prostate cancer treatment in Ehime Prefecture using the hospital-based cancer registry of all designated cancer care hospitals and community cancer care hospitals belonging to the Council of Ehime Cancer Care Hospitals., Methods: Trends of prostate cancer were compared by year according to stage and treatment using data from the hospital-based cancer registry between 2011 and 2020., Results: The number of patients with stage 1 disease increased over time, but the proportion of patients with stage 1 disease among all patients decreased from 65.2% in 2012 to 56.9% in 2020. The number of patients with stage 2 disease also increased, but the proportion of such patients among all patients remained constant. Meanwhile, the proportions of patients with stage 3 or 4 disease increased significantly over time, while that of patients undergoing RP increased from 29.2% in 2011 to 45.7% in 2020 (P < 0.001). The proportion of patients receiving radiotherapy (RT) decreased from 25.8% in 2011 to 17.2% in 2020. The use of hormone therapy (HT) remained unchanged, and the proportion of patients undergoing observation fell from 11.0% in 2011 to 7.0% in 2020. A higher proportion of patients with stage 3 cancer received HT, and RT was more frequently used in stage 3 cancer than in stage 1-2 cancer. The use of HT increased with age., Conclusions: The data highlighted differences in prostate cancer stages and treatment over time. This information could be shared with both urologists and radiologists to improve treatment., (© 2024. The Author(s).)

Objective: To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study, a prospective observational study for Japanese patients, initiated in 2010., Patients and Methods: At the beginning, inclusion criteria were initially low-risk patients, prostate-specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow-up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments., Results: As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64-73) years, 5.3 (4.5-6.6) ng/mL, 0.15 (0.12-0.17) ng/mL, and 1 (1-2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re-biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re-biopsies were 29%, 30%, 35% and 25%, respectively. The 1-, 5- and 10-year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer., Conclusion: Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded., (© 2024 BJU International.)

Background: Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan., Methods: This multicenter prospective observational cohort study enrolled men aged 50-80 years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20 ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6 months and every 3 months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2 years and pathological progression on repeat biopsy., Results: Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70 years, 6.5 ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7 years. At 1 year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15 years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy., Conclusion: Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The Briganti nomogram (cut-off value 5%) is commonly used to determine the indications for pelvic lymph node dissection (PLND) in patients with prostate cancer. We retrospectively analyzed the potential oncological benefit of PLND based on the 5% cut-off value on the Briganti nomogram. We obtained the data from the Medical Investigation Cancer Network (MICAN) Study, which included 3,463 patients who underwent a radical prostatectomy (RP) at nine institutions in Japan between 2010 and 2020. We included patients with Briganti scores ≥ 5% and a follow-up period ≥6 months and excluded patients categorized in the very high-risk group (based on NCCN categories); a final total of the cases of 1,068 patients were analyzed. The biochemical recurrence (BCR)-free survival was significantly worse in the patients who underwent PLND compared to those who did not (p=0.019). A multivariate analysis showed that high prostate-specific antigen (PSA) levels (p<0.001) and an advanced T-stage (p=0.018) were significant prognostic factors for BCR, whereas PLND had no effect on BCR (p=0.059). Thus, PLND in patients with prostate cancer whose Briganti score was 5% did not provide any oncological benefit. Further research is necessary to determine the indication criteria for conducting PLND., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objectives: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD)., Methods: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS)., Results: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS., Conclusions: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer., (© 2024 The Japanese Urological Association.)

Objectives: The use of radical prostatectomy is increasing with the rising incidence of prostate cancer. We assessed the surgical trends related to radical prostatectomy using data from a multi-center, retrospective cohort study, the MICAN (Medical Investigation Cancer Network) study, which was conducted in all the urology-related medical facilities in Ehime Prefecture, Japan., Methods: We compared data from the MICAN study with prostate biopsy registry data collected in Ehime between 2010 and 2020 and recorded the surgical trends., Results: There was a significant increase in the mean age of patients with positive biopsies, and the positivity rate increased from 46.3% in 2010 to 60.5% in 2020, while the number of biopsies obtained decreased. The number of radical prostatectomies performed increased over the years, with robot-assisted radical prostatectomy becoming the predominant procedure. In 2020, robot-assisted radical prostatectomies accounted for 96.0% of the surgeries performed. The age at surgery also gradually increased. Of the registered patients aged ≤75 years, 40.5% underwent surgery in 2010, compared with 83.1% in 2020. The prevalence of surgery also increased from 4.6% to 29.8% in patients aged >75 years. There was a gradual increase in the proportion of high-risk cases, from 29.3% to 44.0%, but a decrease in that of low-risk cases, from 23.8% in 2010 to 11.4% in 2020., Conclusions: We have shown that the number of radical prostatectomies performed in Ehime is increasing in patients aged both ≤75 and >75 years. The proportion of low-risk cases has decreased, while that of high-risk cases has increased., (© 2023 The Japanese Urological Association.)

Objective: Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs., Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group., Results: The predictors were age (<71.4 years), serum levels of C-reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not., Conclusions: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high-risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs., (© 2022 The Japanese Urological Association.)

Background: There is no useful predictive marker for reclassification on active surveillance. Thus, we aimed to investigate thresholds of [-2] proPSA (p2PSA)-related parameters to predict reclassification of the first-year protocol biopsy (1-year PBx) and evaluate the influence of clinical decision-making., Methods: This was an observational, prospective cohort study conducted at 19 Japanese institutes. The inclusion criteria included clinical stage T1c/T2, prostate-specific antigen (PSA) levels ≤10 ng/mL, PSA density <0.2 ng/ml/cc, one or two positive biopsy cores, and Gleason score (GS) ≤6 (GS ≦7 for patients aged ≥70 years) at diagnostic biopsy. All participants were required to receive a blood-sampling test on a protocol visit at inclusion and at the 1-year PBx. PSA and PSA isoforms (free PSA, p2PSA) were measured, and parameters (%free PSA, %p2PSA, phi) were calculated. Multivariable logistic regression models were used to predict the reclassification risk. To assess the predictive power and thresholds for reclassification, we plotted Receiver Operating Characteristic (ROC) curves. Decision curve analysis (DCA) was used to evaluate the variables that yielded a net clinical benefit., Results: A total of 135 patients were included, and 36 patients were reclassified on the 1-year PBx. Multivariate analyses showed that %p2PSA and phi at inclusion and p2PSA, %p2PSA, and phi before the 1-year PBx were significant predictors of reclassification at the 1-year PBx. The ROC analysis showed an optimal cutoff point, sensitivity, and specificity of %p2PSA and phi before the 1-year PBx of 1.64, 86%, 49% and 35.92, 89%, 47%, respectively. The DCA showed that phi before the 1-year PBx had the highest net benefit. The study limitation was its single-arm observational design., Conclusions: %p2PSA and phi before the 1-year PBx had a good prediction power. phi is the most useful indicator for clinical decision-making on active surveillance., Trial Registration: This study is registered atthe Japan Trial Register with ID UMIN000009876 ( https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000011573 )., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: This study aimed to evaluate the pathological findings and oncological outcomes of deferred radical prostatectomy in patients who initially elected for active surveillance in a Japanese cohort., Methods: We retrospectively analyzed data collected from a multi-institutional prospective observational cohort of the Prostate Cancer Research International: Active Surveillance-JAPAN study between January 2010 and September 2020. Triggers for radical prostatectomy were disease progression based on pathological findings of repeat biopsy and patients' request. The primary end point was evaluation of prostate-specific antigen recurrence-free survival. Secondary end points were overall survival and comparison of pathological and oncological outcomes between patients stratified into immediate or late radical prostatectomy group by time to radical prostatectomy., Results: Overall, 162 patients (15.7%) with prostate cancer underwent initial active surveillance followed by radical prostatectomy. The median time to radical prostatectomy was 18 months (interquartile range 14-43.3), and the median postoperative follow-up was 32 months (interquartile range 14-57.5). Prostate-specific antigen recurrence was observed in eight patients (4.9%). The 3-year prostate-specific antigen recurrence-free survival rate was 96.9%. The 5-year overall survival rate was 100%; however, one patient died of another cause. There were no significant differences in pathological findings between immediate and late radical prostatectomy groups. No significant difference in prostate-specific antigen recurrence-free survival was found between the two groups (log-rank p = 0.34)., Conclusions: Radical prostatectomy after active surveillance, as an initial treatment option, does not lead to loss of curative chances in Japanese patients with early-stage prostate cancer in the short follow-up period., (© 2021. Japan Society of Clinical Oncology.)

Objective: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy., Methods: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone-sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration-resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole-body bone scintigraphy using 99m Tc-methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all-cause death including Bone Scan Index, prostate-specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses., Results: During a mean follow-up period of 716 ± 404 days, 81 (33%) of the patients died, and 3-year mortality rates were 20% and 52% in the metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone-sensitive prostate cancer group, whereas prostate-specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration-resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate-specific antigen progression in the metastatic hormone-sensitive prostate cancer group. Patients with metastatic hormone-sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response., Conclusion: The Bone Scan Index and hot spot number are significant determinants of 3-year mortality, and combining the Bone Scan Index with prostate-specific antigen should contribute to the management of prostate cancer patients with bone metastasis., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Purpose: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN)., Methods: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS., Results: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS., Conclusion: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy., Study Registration: Clinical trial registry-UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11)., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca)., Methods: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales., Results: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05)., Conclusion: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Patients with favorable-risk prostate cancer on active surveillance (AS) are strictly followed for safer execution. Repeat protocol biopsy is essential for evaluating cancer aggressiveness. However, the acceptance rate of repeat biopsy is not high enough because of the burdens of biopsy. We assessed the impact of complications after the initial biopsy on repeat protocol biopsy at 1 year using data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study., Methods: We performed a retrospective analysis using a prospective cohort in the PRIAS-JAPAN study. Patients with favorable-risk prostate cancer (n = 856) who consented to participate in the PRIAS-JAPAN study from 2010 to 2018 were enrolled. Follow-up evaluations included regular prostate-specific antigen, digital rectal examination and biopsy. Rates of complications after biopsies and repeat protocol biopsy non-acceptance rate at 1 year were reported. Logistic regression analysis explored the association between the complications after the initial biopsy and repeat protocol biopsy non-acceptance., Results: Altogether, 759 patients (88.7%) actually proceeded to protocol at 1 year. Repeat protocol biopsy non-acceptance rate at 1 year was 14.9%. Regarding complications after the initial biopsy, hematuria (p = 0.028) and pain (p < 0.001) rates were significantly higher in the repeat biopsy non-acceptance group, but infection (p = 0.056) and hematospermia (p = 0.337) rates were not different. On multivariate logistic regression analysis, pain was a significant predictor for repeat protocol biopsy non-acceptance (odds ratio 4.68, 95% confidence interval 1.864-11.75; p = 0.001)., Conclusions: Pain at the initial biopsy negatively impacts patients' compliance with further protocol biopsies during AS.

Background: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT)., Methods: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death., Results: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722)., Conclusions: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa., (© 2020 American Cancer Society.)

Background: LATITUDE was a randomized, double-blind, international and phase 3 study of abiraterone acetate plus prednisone in patients with high-risk metastatic hormone-naïve prostate cancer. In the first interim analysis of LATITUDE (clinical cutoff date: 31 October 2016), significant prolongation in overall survival and radiographic progression-free survival (co-primary endpoints) was observed when compared with placebo. The results of the Japanese subgroup analysis of LATITUDE first interim analysis were consistent with those of the overall population. In this study, overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented (clinical cutoff date: 15 August 2018)., Methods: Abiraterone acetate (1000 mg/day) and prednisone (5 mg/day) were administered orally in the abiraterone acetate plus prednisone group, and matching placebos in the placebo group., Results: Of the 1199 patients included in LATITUDE, 70 constituted the Japanese subgroup (abiraterone acetate plus prednisone: n = 35, placebo: n = 35). Following a median (range) follow-up of 56.6 (2.5, 64.2) months, the median overall survival was not reached in both the treatment arms of the Japanese subgroup (hazard ratio: 0.61; 95% confidence interval: 0.27-1.42; nominal P = 0.2502). A total of 23 deaths (abiraterone acetate plus prednisone: 9 [25.7%], placebo group: 14 [40.0%]) were reported in Japanese subgroup. Grade 3/4 adverse events were reported in 24 (68.6%) and 9 (25.7%) patients in the abiraterone acetate plus prednisone and placebo groups, respectively., Conclusions: In this Japanese subgroup analysis, addition of abiraterone acetate plus prednisone to androgen-deprivation therapy demonstrated favorable efficacy and safety outcomes in patients with newly diagnosed, high-risk metastatic hormone-naïve prostate cancer. Survival benefits observed in the Japanese subgroup first interim analysis were sustained long-term and were consistent with the overall population., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: No standard therapy has been established for localised prostate cancer patients with prostate-specific antigen (PSA) failure after radical prostatectomy (RP)., Objective: To determine whether radiotherapy ± hormone therapy is superior to hormone therapy alone in such patients., Design, Setting, and Participants: This study is a multicentre, randomised, open-label, phase 3 trial. Patients with localised prostate cancer whose PSA concentrations had decreased to <0.1 ng/ml after RP, and then increased to 0.4-1.0 ng/ml, were randomised to the salvage hormone therapy (SHT) group (80 mg bicalutamide [BCL] followed by luteinising hormone-releasing hormone agonist in case of BCL failure) or the salvage radiation therapy (SRT) ± SHT group (64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure). From May 2004 to May 2011, 210 patients (105 in each arm) were registered, with the median follow-up being 5.5 yr., Outcome Measurements and Statistical Analysis: The primary endpoint was time to treatment failure (TTF) of BCL., Results and Limitations: TTF of BCL was significantly longer in the SRT ± SHT group (8.6 yr) than in the SHT group (5.6 yr; hazard ratio 0.56, 90% confidence interval [0.40-0.77]; one-sided p =  0.001). Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure. However, clinical relapse-free survival and overall survival did not differ between the arms. The most frequent grade 3-4 adverse event was erectile dysfunction (83 patients [80%] in the SHT group vs. 76 [74%] in the SRT ± SHT group). Limitations include the short follow-up periods and surrogate endpoint setting to allow definitive conclusions., Conclusions: Initial SRT prolongs TTF of BCL in patients with post-RP PSA failure, indicating that SRT ± SHT is more beneficial than SHT alone., Patient Summary: Patients who have prostate-specific antigen failure after radical prostatectomy benefit from salvage radiation therapy prior to salvage hormone therapy., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To assess patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy., Methods: patient-reported outcomes were evaluated using Expanded Prostate Cancer Index Composite scores at baseline and 1, 3, 6, 12 and 36 months after treatment, respectively, using differences from baseline scores., Results: Urinary function was the same in the three groups at baseline, but worse after surgery than after permanent prostate brachytherapy until 12 months, and similar after open radical prostatectomy and permanent prostate brachytherapy and better than after laparoscopic radical prostatectomy at 36 months. Urinary bother was significantly worse at 1 month after surgery, but better after open radical prostatectomy than after permanent prostate brachytherapy and laparoscopic radical prostatectomy at 3 months, after which symptoms improved gradually in all groups. Obstructive/irritative symptoms were worse after permanent prostate brachytherapy than after open radical prostatectomy at 36 months, and worse after laparoscopic radical prostatectomy until 6 months. Urinary incontinence was worse after surgery, particularly after 1 month. This symptom returned to the baseline level at 12 months after open radical prostatectomy, but recovery after laparoscopic radical prostatectomy was slower. Bowel function after permanent prostate brachytherapy was significantly worse than after surgery at 1 month and this continued until 6 months. Bowel bother was slightly worse at 3 and 6 months after permanent prostate brachytherapy compared to these time points after surgery., Conclusion: Urinary function and bother were worst after laparoscopic radical prostatectomy, especially in the early postoperative phase, whereas urinary obstructive/irritative symptom, bowel function and bother were worse after permanent prostate brachytherapy. These findings are useful and informative for the treatment of patients with prostate cancer., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To present the study design and rationale of Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study aiming to determine the role of the bone scan index, the amount of bone metastasis, in the treatment and prognosis of prostate cancer patients., Methods: A total of 237 patients were recruited at 30 hospitals in Japan. All had prostate cancer with bone metastasis and were scheduled to undergo either hormonal therapy (group H) or chemotherapy (group C). Bone scans were carried out with 99m Tc-methylenediphosphonate. Follow-up studies are planned to continue for 3 years, and changes in biochemical and tumor markers in response to hormonal therapy and chemotherapy will be recorded in addition to skeletal-related events, recurrence, disease progression and death., Results: The basic characteristics of the patients (n = 200) at the time of registration during December 2016 were as follows: mean age 71 ± 8 years; median bone scan index calculated on-site 1.9% (range 0.02-13.3%); median number of hot spots 18 (range 1-128); median prostate-specific antigen 155 ng/mL (range 0.04-22 412 ng/mL); and the most frequent Gleason score 9 (47%). The prostate-specific antigen value was higher in group H than group C (288 vs 33 ng/mL, P < 0.0001), whereas bone scan indexes were comparable (1.7 vs 2.3%, not significant) between the two groups. Liver metastasis was more frequent in group C than group H (6.1% vs 0.8%, P = 0.035)., Conclusions: The baseline characteristics of the Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index database have been established. This collaborative study can now proceed with clarifying the role of the bone scan index for patient management including treatment strategies and prognosis., (© 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: There have been few reports on health-related quality of life (HRQOL) after laparoscopic radical prostatectomy (LRP) in Japanese patients. The aim of this study is to assess changes in HRQOL during 36 months after LRP compared with retropubic radical prostatectomy (RRP)., Methods: The subjects were 105 consecutive patients treated with LRP between 2011 and 2012. HRQOL was evaluated using the International Prostate Symptom Score (IPSS), Medical Outcome Study 8-Items Short Form Health Survey (SF-8), and Expanded Prostate Cancer Index Composite (EPIC) at baseline and 1, 3, 6, 12 and 36 months after surgery. These results were compared with data for 107 consecutive patients treated with RRP between 2005 and 2007. The comparison between LRP and RRP was examined at every time point by Mann-Whitney U-test and chi-square test. Multiple linear regression analysis was used to identify independent factors related to the urinary domain in EPIC., Results: The IPSS change was similar in both groups. The LRP group had a better SF-8 mental component summary score at baseline and a better SF-8 physical component summary score at 1 month after surgery. In EPIC, urinary function and bother were worse after LRP, but improved at 12 months and did not differ significantly from those after RRP; however, these factors then worsened again at 36 months after LRP. Urinary incontinence was also worse at 36 months after LRP, compared to RRP. In patients treated with nerve-sparing surgery, urinary function and urinary incontinence were similar and good at 12 and 36 months in both groups. Bowel function and bother, and sexual function and bother were similar in both groups and showed no changes from 12 to 36 months. Age and salvage radiotherapy were independent predictors of incontinence (daily use of two or more pads) in multivariate analysis. Surgical procedure was not an independent factor for incontinence, but incontinence defined as use of one pad or more was associated with the surgical procedure., Conclusions: Urinary function and bother at 36 months were worse after LRP than after RRP. Age, salvage radiotherapy and surgical procedure were associated with urinary incontinence after 36 months.

This multi-institutional retrospective analysis examined learning curves for dosimetric parameters and operation time after introduction of intraoperatively built custom-linked (IBCL) seeds. Data from consecutive patients treated with seed implantation before and after introduction of IBCL seeds (loose seed, n = 428; IBCL seed, n = 426) were collected from 13 centers. Dose-volume histogram parameters, operation times, and seed migration rates were compared before and after introduction of IBCL seeds. At the 1-month CT analysis, no significant differences were seen in dose to 90% of prostate volume between before and after IBCL seed introduction. No learning curve for dosimetry was seen. Prostate and rectal volume receiving at least 150% of prescription dose (V150 and RV150) were higher in the loose-seed group than in the IBCL-seed group. Operation time was extended by up to 10 min when IBCL seeds were used, although there was a short learning curve of about five patients. The percentage of patients with seed migration in the IBCL-seed group was one-tenth that in the loose-seed group. Our study revealed no dosimetric demerits, no learning curve for dosimetry, and a slightly extended operation time for IBCL seeds. A significant reduction in the rate of seed migration was identified in the IBCL-seed group., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: To define clinical and pathological factors predicting reclassification at the time of 1-year repeat biopsy (re-Bx) based on a Japanese cohort forming part of the Prostate Research International: Active Surveillance (PRIAS) study., Patients and Methods: The inclusion criteria for the PRIAS study are as follows: clinical stage T1c/T2, PSA ≤ 10 ng/ml, PSA density (PSAD) < 0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score (GS) ≤ 6 at initial diagnostic biopsy. Baseline clinical characteristics and prostate-specific antigen doubling time (PSADT) at the time of re-Bx were analyzed via multivariate logistic regression with respect to reclassification and 'no cancer' status on the 1-year re-Bx., Results: A total of 386 patients were enrolled in PRIAS-JAPAN by the end of 2013. Of these, 216 underwent re-Bx at 1 year. A total of 73 patients (33.8 %) were reclassified, whereas 74 (34.3 %) had no cancer. Older age, a higher PSAD, a higher positive core rate, and a shorter PSADT were significant predictors of reclassification. The positive core rate was the predictor common to reclassification, no cancer, and high GS, upon re-Bx., Conclusions: An interim analysis of a Japanese AS cohort participating in PRIAS revealed that the positive core rate was strongly associated with reclassification at the 1-year re-Bx. However, although amendment of the PRIAS inclusion criteria to incorporate a positive core might reduce any concern about underestimation, this would also reduce the number of patients undergoing AS.

Objective: To determine the helpful factors to distinguish prostate-specific antigen failure from prostate-specific antigen bounce with large magnitude., Methods: From October 2004 to December 2009, 242 patients with prostate cancer treated with (125)I brachytherapy were analyzed, 88 patients were excluded because the follow-up durations were shorter than 5 years. Their median follow-up was 80.4 months (60.0-123.9). Prostate-specific antigen failure was determined using the Phoenix definition. Prostate-specific antigen bounce was defined as an increase ≥0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Prostate-specific antigen bounce +2 was defined as a prostate-specific antigen rise by 2.0 ng/ml or more above the nadir., Results: The 5-year biochemical relapse-free survival rate was 90.2%. Prostate-specific antigen failure and prostate-specific antigen bounce +2 were seen in 23 patients (14.9%) and 12 patients (7.8%), respectively. On univariate analysis, age at implant (P = 0.028), T stage (P = 0.020), time to prostate-specific antigen failure or prostate-specific antigen bounce (time to onset) (P = 0.0008), prostate-specific antigen velocity (P = 0.0003) and prostate-specific antigen doubling time (P = 0.0004) were significant for the distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2. On multivariate analysis, no factor was the statistically significant factor. On receiver operating characteristic curve analysis, time to onset with a cutoff value of 29.8 months, prostate-specific antigen velocity of 0.18 ng/ml/month and prostate-specific antigen doubling time of 6.3 months had the highest accuracy of 82.9, 82.9 and 82.9% for prostate-specific antigen failure, respectively., Conclusions: Time to onset, prostate-specific antigen velocity and prostate-specific antigen doubling time would be helpful for distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To assess health-related quality of life in the first year after laparoscopic radical prostatectomy compared with that after open radical prostatectomy., Methods: The subjects were 105 consecutive patients with localized prostate cancer treated with laparoscopic radical prostatectomy between January 2011 and June 2012. Health-related quality of life was evaluated using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and Expanded Prostate Cancer Index Composite at baseline and 1, 3, 6 and 12 months after surgery. Comparisons were made with data for 107 consecutive patients treated with open radical prostatectomy between October 2005 and July 2007., Results: The International Prostate Symptom Score change was similar in each group. The laparoscopic radical prostatectomy group had a better baseline Medical Outcome Study 8-Items Short Form Health Survey mental component summary score and a better Medical Outcome Study 8-Items Short Form Health Survey physical component summary score at 1 month after surgery. In Expanded Prostate Cancer Index Composite, obstructive/irritative symptoms did not differ between the groups, but urinary incontinence was worse until 12 months after surgery and particularly severe after 1 month in the laparoscopic radical prostatectomy group. The rate of severe urinary incontinence was much higher in the laparoscopic radical prostatectomy group in the early period. Urinary bother was worse in the laparoscopic radical prostatectomy group at 1 and 3 months, but did not differ between the groups thereafter. Urinary function and bother were good after nerve sparing procedures and did not differ between the groups. Bowel and sexual function and bother were similar in the two groups., Conclusion: Urinary function in the first year after laparoscopic radical prostatectomy is worse than that after open radical prostatectomy., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The goals of the study were to examine surveillance biopsy and active treatment in patients under active surveillance (AS) for low-risk prostate cancer and to determine the active treatment-free survival rate., Methods: The subjects were 87 patients with low-risk prostate cancer who were under AS between 2000 and 2010. The eligibility criteria for AS were T1c, Gleason score ≤ 6, prostate-specific antigen level ≤ 10 ng/ml, one or two positive biopsies, maximum cancer involvement ≤ 50 %, and age ≤ 80 years old., Results: Of the 87 patients, 48 underwent the first surveillance biopsy (55.2 %). In this biopsy, no cancer was found in 33.3 % of cases, 27.1 % remained eligible for AS, and 39.6 % did not meet the AS criteria (up-grade 22.9 %, up-volume 16.7 %). A second surveillance-biopsy was performed at 1.9 years after the first biopsy. No cancer was found in 20.0 % of cases, 40.0 % remained eligible for AS, and 40.0 % did not meet the AS criteria (up-grade 26.7 %, up-volume 13.3 %). A total of 50 patients received treatment by 1.7 years after starting AS, mainly due to an up-grade or up-volume. However, some patients underwent radiotherapy despite biopsy results indicating no cancer or eligibility for AS. The active treatment-free survival rate was 64.1 % after 2 years., Conclusions: Surveillance biopsy is important for identifying patients who require active treatment. The results in this study allowed determination of the active treatment-free survival rate and are informative for making treatment decisions.

Purpose: We investigated the relationships between hospital surgical volume, surgical outcome, care plans indicated in critical pathways and actual perioperative care using data from a nationwide survey for radical prostatectomy., Materials and Methods: In this study, urologists from 155 hospitals in Japan cooperated in submitting the data of 4,029 patients who underwent radical prostatectomy in 2007, and the perioperative care plan in critical pathways. Of these, we analyzed data of 3,499 patients undergoing open radical prostatectomy and minimum incision endoscopic radical prostatectomy., Results: Increasing hospital volume was associated with decreased proportion of open radical prostatectomy (p < 0.001). As the hospital volume increased, surgical duration was significantly shorter (p < 0.001) and bleeding volume decreased (p < 0.004). Analyses of perioperative care suggested that low-volume hospitals (<15 patients annually) were likely to have longer care than medium-volume (15-29 patients per year) or high-volume (≥30 patients per year) hospitals, and the length of actual care was prolonged in the low-volume hospitals. Multivariate logistic regression analysis suggested that the occurrence of postoperative complications was significantly associated with surgeon's volume (p = 0.004), patient age (p = 0.001), preoperative anticoagulant therapy (p = 0.045), coexistent diabetes mellitus (p = 0.009), surgical duration (p = 0.002) and bleeding volume (p < 0.001), but not hospital volume., Conclusions: Urologists in high-volume hospitals appeared to attempt new types of surgery. Hospital surgical volume was strongly associated with the surgical duration, bleeding volume and planned and actual perioperative care; however, it was not associated with postoperative complications.

Background: There are few reports of long-term treatment with docetaxel in castration-resistant prostate cancer (CRPC) because of the limit of a maximum of ten cycles of treatment in TAX327 showing a survival benefit. Therefore, this study, ARD6563, was conducted to evaluate the safety of more than ten cycles of docetaxel in metastatic CRPC., Methods: We enrolled patients who had received ten cycles of docetaxel in the preceding study, ARD6562. For ARD6563, patients received docetaxel every 3 weeks, at the last dose (70, 60, or 50 mg/m(2)) received for cycle 10 in ARD6562, with prednisolone 5 mg orally twice daily., Results: The safety analysis set comprised 15 patients (median age, 64 years; performance status, 0 in 87%) out of 43 patients treated in ARD6562. The median initial dose of docetaxel was 60 mg/m(2), and the median number of additional cycles administered was 8 (range, 1-42). The relative dose intensity was 78.0% for docetaxel and 98.0% for prednisolone. Dose reduction was needed in 3 cycles because of grade 3 infection, febrile neutropenia, and grade 2 neuropathy. Administration delay was necessitated in 6 cycles because of grade 1-2 nonhematological toxicities. The major grade 3-4 toxicities were myelosuppression. Five patients who had an observed partial response or stable disease in ARD6562 maintained their clinical response in ARD6563. The study treatment was discontinued in 10 patients because of disease progression and in 4 patients for serious toxicities. There were no treatment-related deaths., Conclusions: Long-term docetaxel with prednisolone is feasible in selected Japanese patients with CRPC.

Objectives: To examine the association between cancer location, resection margins and oncological outcome in patients undergoing radical prostatectomy., Methods: A total of 505 patients who underwent radical prostatectomy between 1993 and 2009 were included in this analysis. Cancer location, resection margins and pathological factors were assessed based on the 2010 General Rules for Clinical and Pathological Studies on Prostate Cancer. Biochemical recurrence was defined as prostate-specific antigen >0.2 ng/mL., Results: Positive resection margins were found in 38.4% of all cases, in 30.3% of pT2 cases and in 57.7% of pT3 cases. The cancer was distributed evenly among the apex-anterior, apex-posterior and middle lesions, which each accounted for approximately 30% of the whole lesion in the main tumor. A higher rate of positive resection margins (47.6%) was found in the apex-anterior lesions. In minor tumors, most cancer was located in the middle lesion and accounted for approximately 60% of the lesion. However, positive resection margins were detected significantly more frequently in the apex-anterior lesion of minor tumors. The 5-year and 10-year biochemical recurrence-free survival rates were 36.2% and 32.0%, respectively, in patients with a positive resection margin, and 82.7% and 77.4%, respectively, in those with a negative resection margin. Cancer location was an independent risk factor for biochemical recurrence and a positive resection margin. Recurrence-free survival was lower in pT2 cases with a positive resection margin compared with pT3 cases with a negative resection margin., Conclusions: Cancer location and occurrence of positive resection margins can have negative effects on recurrence-free survival. Thus, it is of utmost importance to avoid positive resection margins during radical prostatectomy., (© 2012 The Japanese Urological Association.)

Objectives: To examine quality of life (QOL) for 3 years after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (PPB) and to determine differences between the two procedures., Methods: In all 107 patients who underwent RRP and 91 who received PPB between October 2005 and July 2007 were included in this study. QOL surveys were performed using the international prostate symptom score (IPSS), the Medical Outcome Study 8-items short form health survey and the expanded prostate cancer index composite at baseline and 1, 3, 6, 12 and 36 months after treatment., Results: At 3 years, all parameters for general QOL and almost all for disease-specific QOL were similar to those at 12 months. Urinary continence after RRP slightly improved from 12 months to 3 years, but it was still significantly worse than that after PPB. Scores for urinary irritation or obstruction and for bowel function and bother at 3 years were similar between the two groups. Sexual function and bother did not change between 12 months and 3 years in either group. Sexual function at 3 years after RRP was worse than that after PPB. Recovery from urinary incontinence and sexual function after RRP with nerve sparing were similar to those after PPB. Urinary incontinence at 3 years correlated with the treatment method and patients' age, whereas urinary irritation/obstruction and urinary bother correlated with the pre-treatment IPSS., Conclusion: QOL assessment represents an important issue in prostate cancer management. Our findings are likely to be of aid in the development of a treatment plan for prostate cancer patients., (© 2011 The Japanese Urological Association.)

Objectives: This study examined the rate of Gleason pattern 5 and the influence of tertiary Gleason pattern 5 on oncological outcomes., Methods: Four hundred sixty-six patients underwent a radical prostatectomy between 1993 and 2008. Each surgical specimen was reviewed and assessed for the tumor diameter, Gleason score (which was based on the 2005 International Society of Urological Pathology Consensus Conference criteria) and the percentage of Gleason pattern 5., Results: The median patient age was 68.0 years old and the median prostate-specific antigen level was 9.28 ng/ml. A tertiary Gleason pattern 5 was present in 24.2% of patients with a Gleason score of <9; in 12.2% of patients with a Gleason score of 3 + 4 and in 45.9% of patients with a Gleason score of 4 + 3. A multivariate analysis showed that a tertiary Gleason pattern 5 was not independently associated with biochemical recurrence-free survival among patients in the Gleason score of 7 and 8 pN0 groups. One hundred eighty-seven patients had any rate of Gleason pattern 5 and significantly worse pathological factors, compared with patients who did not have this pattern. A multivariate analysis of all patients showed that the surgical margin, Gleason score, prostate-specific antigen level and pathological stage were all independent predictors of biochemical recurrence. However, the rate of Gleason pattern 5 was not an independent factor., Conclusions: Tertiary Gleason pattern 5 was not a significant predictive factor for biochemical recurrence. The rate of Gleason pattern 5 was associated with adverse pathological factors.

Objective: To evaluate the efficacy and toxicity of docetaxel plus prednisolone treatment in Japanese patients with hormone-refractory prostate cancer (HRPC)., Methods: From April 2004 through August 2008, we used docetaxel plus prednisolone to treat 55 HRPC patients (median age, 72 years). Eighteen patients (32.7%) had measurable soft tissue lesions, whereas 52 patients (94.5%) had bone metastases. During the 21-day treatment cycle, docetaxel (70 mg/m(2)) was administered once every 21 days and oral prednisolone (5 mg), twice daily. Prostate-specific antigen (PSA) response, defined as a reduction of at least 50% in the baseline levels for 4 weeks, was evaluated., Results: The median follow-up period was 30.1 months; median overall survival, 15.3 months and median progression-free survival, 7.5 months. During follow-up, 37 patients (67.3%) achieved the PSA response, and 5 of 18 (27.8%) patients with measurable disease showed a partial response. Among the 27 patients who experienced cancer pain before treatment initiation, 15 (55.5%) reduced their analgesic drug intake. Multivariate analysis of the prognostic variables revealed a significant association between the overall survival and pain (P = 0.033). Hematological toxicity (grades 3-4) included neutropenia (87.3%), febrile neutropenia (25.5%) and thrombocytopenia (5.5%). Frequent non-hematological adverse events were general edema (52.7%), general fatigue (32.7%) and sensory neuropathy (30.9%). Three patients died of adult respiratory distress syndrome (ARDS)., Conclusion: Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did.

Objective: To assess the efficacy and safety of dietary supplements in patients with early stage prostate cancers who are managed expectantly., Methods: Seventy-four patients with early prostate cancer, who were treated with expectant management, enrolled in the study. A mushroom mycelium extract was given at a dose of 4.5 g/day for 6 months. The primary endpoint was the proportion of patients in which the prostate specific antigen level decreased by 50% or more following treatment. The adverse events, change of prostate specific antigen value and quality of life were also evaluated., Results: In only one of 74 patients (1.4%), the prostate specific antigen value decreased more than 50%. Grade 2 diarrhea and grade 1 itching were observed in one patient, and patient ingestion compliance was maintained near 100%. The alternation of prostate specific antigen values was stable before and after treatment. In subjects with strong anxiety prior to supplement ingestion, these feelings were significantly alleviated (state anxiety, P = 0.0018; trait anxiety, P = 0.0099)., Conclusions: In this phase II study of early prostate cancer patients who were managed expectantly, a mushroom mycelium extract was an ineffective treatment for reducing 50% or more the patient prostate specific antigen values.

Objective: The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute., Methods: Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively., Results: The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group., Conclusions: This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions.

We report a case of radiation pneumonitis caused by a migrated seed lodged in the lung after prostate brachytherapy. A 71-year-old man underwent transperineal interstitial permanent prostate brachytherapy for localized prostate cancer. On the day after brachytherapy, a routine postimplant chest X-ray revealed migration of one seed to the lower lobe of the left lung. After 1 month, pulmonary opacities were observed in the left lower lobe but not near the seed. He was diagnosed with bacterial pneumonia, and antibiotic therapy was commenced. Two months after brachytherapy, the patient's symptoms, laboratory data and pulmonary opacities improved; however, an abnormal shadow (consolidation) developed around the migrated seed. Lung consolidation disappeared almost completely 12 months after brachytherapy without any medical treatment. The abnormal shadow probably represented radiation pneumonitis. To the best of our knowledge, this is the first report of radiation pneumonitis caused by a migrated brachytherapy seed in the lung.

Objective: The health-related quality of life (HRQOL) after a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) was prospectively compared at a single institute., Methods: Between 2003 and 2005, 122 patients were treated by RRP and 82 patients were treated by PPB. A QOL survey was completed at baseline, and 1, 3, 6 and 12 months after treatment, prospectively., Results: The general HRQOL was not different between the RRP and PPB groups after 3 months. However, at 1 month after treatment, the general HRQOL scores, except for general health, were significantly better in the PPB group than that in the RRP group. Moreover, the disease-specific QOL was worse in urinary and sexual functions in the RRP group. Urinary function in the RRP group had not recovered to baseline after 12 months. Although the urinary function in the PPB group was better than that of the RRP group, urinary bother continued to worsen until 6 months and thereafter it recovered gradually. The bowel function was not worse in the PPB group but bowel bother was worse at 6 months in the PPB group. In the RRP group, the patients with nerve sparing demonstrated better in sexual function than those without nerve sparing, but the recovery did not reach the level of the PPB group., Conclusions: This prospective study revealed the differences in the QOL after RRP and PPB. These results will be helpful for making treatment decisions.

A 75-year-old man was referred to our department with prostate cancer. When our pathologist reviewed the biopsy specimen, he was diagnosed as intraductal urothelial carcinoma. Transurethral random biopsy showed the urothelial carcinoma in the prostate ducts but no cancer in the bladder. He was diagnosed as primary urothelial carcinoma of the prostate ducts (cTis pd cN0 M0), and radical cystoprostatectomy were performed. Histopathological examination showed urothelial carcinoma in situ spread along ducts and ejaculatory ducts and into seminal vesicles but there was not invasion of prostatic stroma. (pTis pd pN0 M0 Urothelial carcinoma G3 pL0 pV0) He had no adjuvant therapy, he is alive without any evidence of tumor recurrence after surgery.

From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH) agonist, 49 patients with anti-androgen (bicaltamide/flutamide), and 48 patients with maximum androgen blockade (MAB). The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml), and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction). The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.

A total of 42 patients with hormone-refractory prostate cancer received E-E therapy. Oral estramustine phosphate (EMP) was administered twice daily for a total daily dose of 560 mg every day and oral etoposide (E-E therapy, 50 mg/body/day) was given on days 1-21 and stopped on days 22-35. Treatment was continued until the disease progression was confirmed radiographically or PSA had increased from base line of at least 25%. The median follow-up period after E-E therapy was 77.4 months (range : 12.5 to 122.3). Nineteen patients (43%) achieved a PSA decrease of 50% or greater. The median survival time of the patients who had a decrease of 50% or greater in the PSA value (PSA responder) was 29.3 months and the patients who did not (PSA non-responder) was 14.1 months (p = 0.01). There were no significant differences between PSA responders and non-responders when taking into account variables. Excluding those patients with only PSA elevation, the survival time was 14.9 months with no significant difference between PSA responders and non-responders. The toxicities (grade 3 or more) were identified as anemia, leukocytopenia thrombocytopenia, cardiovascular events, and gastrointestinal and hepatic disorders, which occurred in 0, 5, 2, 2, 14, and 2% of the patients, respectively. E-E therapy was considered to be an active oral regimen and well-tolerated for outpatients with hormone-refractory prostate cancer in Japanese patients.

Between April 2004 and August 2005, we used docetaxel in combination with prednisolone to treat 14 patients with hormone-refractory prostate cancer (HRPC). Docetaxel was administered at a dose of 70 mg/m2 once every 21 days and oral prednisolone 5 mg was administered twice daily concurrently on days 1-21. The treatment was continued until disease progression or unacceptable adverse events occurred. Prostate specific antigen (PSA) was used as a tumor marker. PSA response was defined as a reduction from baseline of at least 50% that was maintained for 4 weeks. Five patients had measurable soft tissue lesions, which were nodal metastases in 4 and liver metastasis in 1. The median follow-up was 8.4 months. During follow-up, 5 patients died. The median treatment cycle was 7 cycles. Manifestations of hematologic toxicity included 11 patients (78%) with grade 3/4 neutropenia and only I with febrile neutropenia. Two patients with gastric hemorrhage and febrile neutropenia needed hospitalization. During follow-up, 8 patients (57%) achieved a PSA reduction from baseline of at least 50%. Three patients with nodal metastases and 1 patient with liver metastasis had partial response. Combined docetaxel and prednisolone was shown to be effective and feasible in Japanese patients.

We have experienced a patient with tumor fever from hormone-refractory prostate cancer (HRPC) who was treated successfully using docetaxel plus prednisolone therapy. A 65-year-old male was diagnosed with prostate cancer (T4 N1 M1b). He received androgen-ablation therapy. But six months later he was confirmed to show failure of the previous hormone therapy and disease progression even after anti-androgen withdrawal. Then docetaxel plus prednisolone therapy was started. After two courses of this therapy, the PSA level decreased by 50% or more, and after ten courses an improvement was seen on the bone scan. The patient has survived for twelve months after starting docetaxel plus prednisolone therapy, without serious adverse events.

Purpose: It is not rare that the repeat biopsy is performed when the initial biopsy was negative. However, there is not a clear indication for the repeat biopsy. We evaluated the utility of prostate specific antigen doubling time (PSA-DT) as indication for the repeat biopsy., Materials and Methods: Of men 103 underwent repeat biopsy after initial negative prostate biopsy, 55 men who had three or more serial PSA measurements until repeat biopsy were evaluated. PSA-DT was calculated using a log-linear regression model and compared with other PSA-related parameters., Results: Prostate cancer was diagnosed in 22 patients (40.0%). Mean PSA-DT in 55 patients was 59.3 months. Comparing of repeat positive biopsy group and negative group, PSA density (PSAD) and PSA velocity (PSAV) in the positive biopsy group were significantly greater than in the negative biopsy group. Age, serum PSA concentration at initial and repeat biopsy, PSA adjusted for volume of transition zone (PSATZ), free to total PSA ratio (%F/T) did not recognize significant differences between both biopsy groups. PSA-DT of positive biopsy group (35.1 months) was significantly shorter than that of negative biopsy group (76.5 months). None was diagnosed prostate cancer whose PSA-DT was longer than 96 months., Conclusion: When we considered prostate repeat biopsy, it was thought that PSA-DT could be one important material, but it was limitation for indication as to other PSA-related parameters.

Purpose: We investigated retrospectively that change of serum testosterone and PSA concentrations following withdrawal of androgen ablation after combination of radiation and hormone therapy for prostate cancer., Subjects and Method: Among prostate cancer patients who were treated with combination of radiation and hormone therapy from 1992, 42 patients who were measured with time in the concentration of testosterone after withdrawal of androgen ablation were selected. Their median age was 76 years old (62-84), their median PSA was 13.2 ng/ml (1.4-215.3), and clinical stage consisted of T1 (12 patients), T2 (12 patients) and T3 (18 patients). They were divided into three groups by recovery of testosterone after withdrawal of androgen ablation and examined with change of PSA. Three groups consisted of castration-level group (testosterone: less than 1.0 ng/ml), low group (1.0-2.0 ng/ ml) and normal group (2.0 ng/ml and more)., Results: There were 8 patients in castration-level group, 10 patients in low group and 24 patients in normal group. There were no significant differences in age, clinical stage and histological grade among each group. However, duration of hormone therapy in normal group was 4.7 months and shorter than durations in castration-level (38.5 months) and low group (26.6 months). The median time of the recovery to normal range of testosterone was 9.1 months. Only duration of hormone therapy influenced the recovery of testosterone in the multivariate analysis. Median changes of PSA after withdrawal of androgen ablation were 0 ng/ml (0-0.029) in castration-level group, 0.118 ng/ml (0-1.169) in low group and 0.427 ng/ml (0.047-4.358) in normal group. Change of PSA in normal group was significantly higher than castration-level and low groups. If the patients were defined as failure in whom PSA was rising during follow-up, positive or negative predictive value to predict failure, when setting a cutoff value to 0.2 ng/ml of PSA rise-width, were better than other cutoff values (0.1 or 0.3 ng/ml)., Conclusion: Among prostate cancer patients treated with combination of radiation and hormone therapy, PSA is went up in some of them with recovery of testosterone after withdrawal androgen ablation. Rise-width of PSA may be important for one of the predictors of failure with measurement of testosterone.

Background: Until 1998 in Japan, very few institutions were treating prostate cancer solely with radiotherapy (RT) >70 Gy and most were using < or =65 Gy in combination with hormone therapy. The present study reports the long-term results of RT combined with hormone therapy for localized and locally advanced prostate cancer., Methods: We investigated 57 patients who were treated by external beam RT plus hormone therapy (median age 79 years, median prostate-specific antigen concentration 15.0 ng/ml) between 1992 and 1998. Patients received 40 Gy of radiation to the pelvis and an additional 20 Gy as a prostatic boost. Hormone therapy was begun on the first day of irradiation and continued thereafter., Results: The median follow-up was 93.3 months and the 5 and 10 year actual overall survival rates were 67.8 and 32.6%, respectively, with 5 and 10 year cause-specific survival rates of 97.9 and 95.0%, respectively. The expected survival rate was 66.2% at 5 years, and overall survival was above expected survival. Only one patient developed severe proctitis (Grade 3). The 5 year occurrence of Grade 1/2 genitourinary toxicity was 23.2%., Conclusions: Combined RT and hormone therapy has a good long-term outcome without severe adverse events. The overall survival rate compares well with the expected survival rate.

Purpose: We compared general and disease specific health related quality of life (QOL) after surgery and radiotherapy for prostate cancer., Materials and Methods: We performed a retrospective survey of patients treated between 1992 and 2001. General and disease specific health related QOL were assessed by the SF-36 and the University of California-Los Angels Prostate Cancer Index (UCLA PCI). We mailed questionnaires of QOL survey and obtained from 143 and 73 men who treated surgery and radiotherapy. The median ages of surgery and radiation group were 70.9 and 79.2 years old, and the median periods after treatment were 2.7 and 2.0 years, respectively., Results: Physical function, role physical, social functioning and mental health were higher score in surgery group than radiation group, however, general health perceptions was higher in radiation group among SF-36. Surgery group had worse urinary function and better sexual function compared with radiation group. Multi-variable analysis showed that scores of social functioning, mental health and sexual function were most influenced by each modality, the scores of physical function, role physical, urinary function and sexual bother were most influenced by age, and the score of general health perceptions and body pain was most influenced by the existence of recurrence. CONSIDERATION: This cross-sectional survey cleared the differences of QOL after surgery and radiotherapy, and the influences of each modality. However, because of difference in background of each group, longitudinal investigation will need to aid patients in the decision making process.

Background: We assessed predictors of response to salvage radiotherapy (sRT) in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy., Methods: A total of 21 patients receiving sRT for PSA recurrence without systemic progression after radical prostatectomy had medical records available for retrospective review. We defined sRT as external beam radiotherapy for patients with a continuous increase in PSA level > or =0.2 ng/ml after radical prostatectomy. Response was defined as achievement of a PSA nadir of < or =0.1 ng/ml. Various pre-treatment parameters were evaluated retrospectively., Results: The median follow-up period after sRT was 38 months. Of the 21 patients, 15 were good responders (71%). The only predictive factor was PSA doubling time (PSADT). Age and PSA level at diagnosis, Gleason score and surgical margin status were not significant predictors of response. The median PSADT in responders was 6.2 months versus 1.9 months in non-responders (P = 0.019). The patients with a PSADT of > or =5 months were all responders., Conclusion: PSADT appears to be a good predictor of response to sRT. sRT was especially effective when PSADT was > or =5 months.

Second cancer after radiotherapy is defined that more than five years have passed from radiotherapy for primary cancer in case of solid and different histological cancer and second cancer exists into or near radiotherapy area. While it has been not frequent that a treatment for urological cancers causes second cancer, there is the possibility that second cancer increases by recent increase of radiotherapy for prostate cancer. We report two cases of second bladder cancer after radiotherapy for prostate cancer. It is important to take second cancer into consideration for long-term after the patients are treated with radiotherapy.

Background: Health-related quality of life (HR-QOL) is important when considering the treatment options for prostate cancer., Methods: From 1992 to 1998, 57 patients were treated by radiotherapy plus hormone therapy (median age, 79 years; median prostate-specific antigen concentration, 15.0 ng/ml; median radiotherapy dosage, 60 Gy). General HR-QOL was measured by the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, and a newly developed disease-specific QOL survey was used to assess urinary and bowel functions. QOL was also measured in a control group of patients admitted for prostate biopsy., Results: The general HR-QOL scores in the radiation group ranged from 70.0 to 91.3, with sexual problems showing the lowest (i.e., worst) score (38.5). Compared with the control group, the scores in the radiation group were worse for physical function and sexual problems. For disease-specific QOL, the radiation group had worse urinary function than controls, but were more satisfied with their urinary function. There was no difference between the radiation group and controls in satisfaction with bowel function. When the control group was subdivided at into two groups: age 75 years or less, and age over 75 years, the QOL score in the radiation group was the same as that in the subgroup aged over 75 years. In subgroups of the radiation patients, according to survey period, there was no difference between the first and last surveys in longitudinal HR-QOL evaluations. The 5- and 10-year overall survival rates were 67.6% and 41.6%, respectively, and the 5- and 10-year cause-specific survival rates were 97.9% and 94.7%., Conclusion: The combination of radiotherapy and hormone therapy has a good outcome and patients do not experience poor HR-QOL, except for sexual problems. Moreover, the disease-specific QOL is good, especially for urinary bother.