Prostatic Neoplasms: Hirao Y

Tanaka M, Ono Y, Matsuda T, Terachi T, Suzuki K, Baba S, Hara I, Hirao Y, Anonymous00107. · Department of Urology, Fukuoka University Faculty of Medicine, Fukuoka, Japan. ~u.ac.jp · Int J Urol. · Pubmed #19228223 No free full text.

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Kamidono S, Ohshima S, Hirao Y, Suzuki K, Arai Y, Fujimoto H, Egawa S, Akaza H, Hara I, Hinotsu S, Kakehi Y, Hasegawa T, Anonymous00384. · No affiliation provided · Int J Urol. · Pubmed #18184166 No free full text.

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Akaza H, Hinotsu S, Usami M, Ogawa O, Kagawa S, Kitamura T, Tsukamoto T, Naito S, Hirao Y, Murai M, Yamanaka H, Namiki M. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8578, Japan. · J Urol. · Pubmed #17084166 No free full text.

Abstract: PURPOSE: We analyzed the outcome of primary androgen depletion therapy, which has gained more attention as a potential therapeutic option in patients with localized or locally advanced prostate cancer as it has been increasingly implemented despite limited data on its therapeutic impact in Japan and the United States. MATERIALS AND METHODS: We analyzed data from CaPSURE and the Japanese Prostate Cancer study. RESULTS: In Japan primary androgen depletion therapy has long been the treatment of choice for localized and locally advanced prostate cancer. Based on CaPSURE data the frequency of primary androgen depletion therapy being chosen to treat localized and locally advanced disease is also increasing in clinical practice in the United States. A study of the outcomes of endocrine therapy is currently being performed in Japan by the Japanese Prostate Cancer Study Group. CONCLUSIONS: It is important to obtain such information about the role of primary androgen depletion therapy for localized and locally advanced prostate cancer from studies of natural history and clinical trials. It is also important to update practical treatment guidelines.

Akaza H, Chodak GW, Hirao Y. · Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba. · Gan To Kagaku Ryoho. · Pubmed #16227758 No free full text.

Abstract: Prostate cancer is a relatively slow-growing disease compared to other cancers, and the patients tend to be older. Taking into consideration therefore life expectancy of the patients and risks of recurrence and progression, conservative treatments (mainly hormonal therapy) are often applied for early cases, as well as radical treatments (total prostatectomy and radiotherapy). Particularly in Japan, many patients start treatment with hormonal therapy alone, in both early and advanced cases. Hence, Maximal Androgen Blockade (MAB) therapy, in which surgical or medical castration (such as LH-RH agonist treatment) and anti-androgen treatment are combined, is widely exercised with the hope to enhance treatment effects. The usefulness of MAB therapy has been assessed in a number of randomized comparative studies, covering mainly metastatic cases. The efficacy of the therapy with the use of flutamide as non-steroidal anti-androgen has been confirmed in some of the studies, although the magnitude of the efficacy cannot be said major. In Phase III clinical studies of MAB therapy with bicalutamide being conducted in Japan for patients in Stages C and D, however, the patient group treated with MAB therapy demonstrated more favorable results compared to the group treated with LH-RH agonist alone, particularly in terms of time to progression (TTP) of the patients in Stage C. These are relatively new findings on the usefulness and adaptability of MAB therapy. In this Panel Discussion, views and experiences are exchanged on a wide variety of topics covering the real usefulness of MAB therapy, its adaptability, possible outcomes of hormonal therapy in early cases, and the future of MAB therapy, taking into account the prevailing opinions and current practices on prostate cancer in both the United States and Japan.

Akaza H, Hirao Y, Labrie F, Soloway MS. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba. · Hinyokika Kiyo. · Pubmed #14978964 No free full text.

Abstract: The authors consider current and future prospects for primary hormone therapy in localized and locally advanced prostate cancer by comparing this form of treatment (hormone monotherapy) with neoadjuvant radiation therapy and radical prostatectomy. Neoadjuvant hormone therapy prior to radiation therapy has been proven effective in recent years, and currently the United States is showing a year-by-year increase in the use of androgen blocking agents during the early stage of prostate cancer. A survey of recent research findings, clearly showed that, for patients with localized prostate cancer, there is no significant difference in survival rate between hormone monotherapy and radical prostatectomy. In the future we can expect to see an increase in available treatment options for localized and locally advanced prostate cancer, with the optimal therapy for each individual patient to be selected by the attending physician in discussion with the patient.

Morikawa H, Cho M, Takada S, Fujimoto K, Uemura H, Ozono S, Hirao Y, Natsume O. · Department of Urology, Nara Medical University. · Hinyokika Kiyo. · Pubmed #12894737 No free full text.

Abstract: A 77-year-old man was referred to our hospital with a complaint of dysuria and right ischiodynia. He had had a hemi-thyroidectomy for thyroid cancer and right cervical lymphadenectomy three years and one year, respectively, before this visit. Prostate cancer was strongly suspected by transrectal examination with prostate specific antigen (PSA) elevated to 77.8 ng/ml. Pathological diagnosis of prostate biopsy specimen was transitional cell carcinoma with grade 3 malignancy and negative staining for PSA. Endoscopic examination showed a normal appearance of bladder and prostatic urethral epithelium. Urine cytology showed no malignant cells. However, immunostaining for PSA revealed that the cervical lymph node specimen resected before was moderately differentiated adenocarcinoma of prostate. He had multiple metastases to mediastinal and retroperitoneal lymph nodes and right ischium. Endocrine therapy (goserelin acetate depot, bicalutamide) and systemic chemotherapy (methotrexate, epirubicin, cisplatin) were performed combined with irradiation to right ischium metastasis. Two months later, he showed a complete response in PSA and partial response in lymph node metastases, but died of cancer 13 months later.

Hirao Y, Cho M. · Department of Urology, Nara Medical University. · Nippon Rinsho. · Pubmed #12599545 No free full text.

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Ozono S, Hirao Y. · Department of Urology, Nara Medical University. · Nippon Rinsho. · Pubmed #11022715 No free full text.

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Arai Y, Akaza H, Deguchi T, Fujisawa M, Hayashi M, Hirao Y, Kanetake H, Naito S, Namiki M, Tachibana M, Usami M, Ohashi Y. · Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. · J Cancer Res Clin Oncol. · Pubmed #18491137 No free full text.

Abstract: PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Uchida T, Baba S, Irie A, Soh S, Masumori N, Tsukamoto T, Nakatsu H, Fujimoto H, Kakizoe T, Ueda T, Ichikawa T, Ohta N, Kitamura T, Sumitomo M, Hayakawa M, Aoyagi T, Tachibana M, Ikeda R, Suzuki K, Tsuru N, Suzuki K, Ozono S, Fujimoto K, Hirao Y, Monden K, Nasu Y, Kumon H, Nishi K, Ueda S, Koga H, Naitoh S. · The Department of Urology, Tokai University Hachioji Hospital. · Hinyokika Kiyo. · Pubmed #16285617 No free full text.

Abstract: We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Homma Y, Akaza H, Okada K, Yokoyama M, Moriyama N, Usami M, Hirao Y, Tsushima T, Sakamoto A, Ohashi Y, Aso Y, Anonymous00039. · Department of Urology, University of Tokyo, Tokyo, Japan. · Int J Urol. · Pubmed #15147545 No free full text.

Abstract: 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 A(2), 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.

Homma Y, Akaza H, Okada K, Yokoyama M, Usami M, Hirao Y, Tsushima T, Sakamoto A, Ohashi Y, Aso Y, Anonymous00367. · Department of Urology, University of Tokyo, Tokyo, Japan. · Int J Urol. · Pubmed #15028100 No free full text.

Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Akaza H, Homma Y, Okada K, Yokoyama M, Usami M, Hirao Y, Tsushima T, Ohashi Y, Aso Y, Anonymous00383. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. · BJU Int. · Pubmed #12614246 No free full text.

Abstract: OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.

Uemura H, Cho M, Hirao Y, Konishi N. · Department of Urology, Nara Medical University. · Hinyokika Kiyo. · Pubmed #12512148 No free full text.

Abstract: We investigated whether the histopathological effect (cell viability) of neoadjuvant hormonal treatment before radical prostatectomy for clinically localized prostate cancer is involved in the biochemical outcome, i.e., androgen independency. Non-randomized prospective trial was carried out between September 1996 and April 2001 involving the patients with clinical stage T1-3 prostate cancer, including 62 who underwent radical prostatectomy after receiving neoadjuvant hormonal treatment for an average of 6.3 months and 76 who underwent radical prostectomy only. All resected specimens were histopathologically diagnosed by whole section analysis. The patients receiving neoadjuvant hormonal treatment were categorized into 4 groups according to the histological change in the resected prostate. There were 8 patients in G0 (all viable cells), 11 patients in G1 (more than 50% viable cells), 26 patients G2 (more than 50% non-viable cells) and 17 patients in G3 (no cancer cells). No difference in the patient background (prostate specific antigen, stage, Gleason score, positive core Nr, duration of neoadjuvant therapy) was observed in any group, except for the duration of (p < 0.05). Multivariate hazards analyses revealed that only the duration of neoadjuvant hormonal treatment was independently associated with excellent responders with grade 3 histological effect. Neoadjuvant hormonal therapy prior to radical operation resulted in various histopathological changes in the prostate, but it is not clear whether the histological effects of hormonal treatment might be involved in the outcome. A longer follow-up randomized prospective trial is necessary.

Ozono S, Yamaguchi A, Mochizuki H, Kawakami T, Fujimoto K, Otani T, Yoshida K, Ichinei M, Yamashita T, Hirao Y. · Department of Urology, Nara Medical University, Nara, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #12497002 links to  free full text

Abstract: The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.

Ozono S, Okajima E, Yamaguchi A, Yoshikawa M, Iwai A, Moriya A, Yoshida K, Samma S, Maruyama Y, Hirao Y. · Department of Urology, Nara Medical University, Kashihara, Japan. · Jpn J Clin Oncol. · Pubmed #11095136 links to  free full text

Abstract: BACKGROUND: A randomized multicenter study was conducted to investigate the efficacy of total androgen blockade (TAB) for patients with previously untreated prostate cancer using the steroidal anti-androgen chlormadinone acetate (CMA) and the non-steroidal anti-androgen flutamide. We also compared the liver dysfunction in these two arms. METHODS: From November 1995 to October 1997, 71 patients were registered into this study and 70 of them were eligible. RESULTS: There was no significant difference in the efficacy of TAB between CMA and flutamide at 24 weeks. The testosterone and prostate-specific antigen (PSA) levels in patients administered flutamide (Group II) increased significantly 3 days after the first dose of LH-RH analog, whereas no such increase was observed in patients administered CMA (Group I), indicating that CMA prevented the flare-up. Parameters of liver function, serum GOT and GPT levels, which were normal at the baseline, became abnormal in 30.0% and 35.3%, respectively, of patients in Group II. These figures were significantly higher than the corresponding figures of 6.3% and 12.5%, respectively, in Group I. When the degree of change in each of these parameters was analyzed, both GOT and GPT levels showed a significantly greater increase in Group II than in Group I. CONCLUSION: These results indicate that attention must be paid to changes in liver function during the administration of flutamide in patients with prostate cancer even if their baseline liver function is normal. It is also suggested that CMA may be better tolerated from the viewpoint of the drug effects on liver function.

Akaza H, Homma Y, Okada K, Yokoyama M, Moriyama N, Usami M, Hirao Y, Tsushima T, Ohashi Y, Aso Y. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. · Jpn J Clin Oncol. · Pubmed #10798540 links to  free full text

Abstract: BACKGROUND: The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. METHODS: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. RESULTS: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p<0.05). Group II showed a longer progression-free survival (p <0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. CONCLUSIONS: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

Kotake T, Usami M, Akaza H, Koiso K, Homma Y, Kawabe K, Aso Y, Orikasa S, Shimazaki J, Isaka S, Yoshida O, Hirao Y, Okajima E, Naito S, Kumazawa J, Kanetake H, Saito Y, Ohi Y, Ohashi Y. · Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. · Jpn J Clin Oncol. · Pubmed #10678560 links to  free full text

Abstract: OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Homma Y, Akaza H, Okada K, Yokoyama M, Moriyama N, Usami M, Hirao Y, Tsushima T, Sakamoto A, Ohashi Y, Aso Y. · Department of Urology, University of Tokyo, Japan. · Int J Urol. · Pubmed #10375185 No free full text.

Abstract: 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 >0.2ng/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.

Nakai Y, Tanaka M, Yoshikawa M, Tanaka N, Hirayama A, Fujimoto K, Hirao Y, Inoue T, Akiyama T. · Department of Urology, Nara Medical University. · Hinyokika Kiyo. · Pubmed #19227214 No free full text.

Abstract: We report a case of prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. A 62-year-old man was admitted to our hospital for treatment of prostate cancer with cyst formation. On the rectal examination, a cystic tumor was palpable on the left side of prostate. The left kidney was not detected by intravenous pyelography and ultrasonography. Magnetic resonance imaging revealed a retrovesical cystic lesion in the left side. Total prostatectomy and left ureterectomy were performed under the diagnosis of clinical T1cN0M0 prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. The pathological findings showed well differentiated adenocarcinoma, Gleason score 3 + 3, and left ectopic ureter entering into the seminal vesicle and left renal agenesis. The patient was well 39 months after the total prostatectomy and left ureterectomy without evidence of recurrence. There have been no cases of the association of this urogenital anomaly, such as ectopic ureter opening to seminal vesicle with renal agenesis and prostate cancer and the combined management of both. Our case seems to be first case in the Japanese literature.

Tanaka N, Asakawa I, Kondo H, Tanaka M, Fujimoto K, Hasegawa M, Konishi N, Hirao Y. · Department of Urology, Nara Medical University, Kashihara, Nara, Japan. · Int J Urol. · Pubmed #19120529 No free full text.

Abstract: OBJECTIVES: To assess our initial experience in the treatment of localized prostate cancer using low-dose-rate brachytherapy (LDR-brachytherapy) with iodine-125. METHODS: One-hundred consecutive patients received LDR-brachytherapy between July 2004 and October 2006. Seventy-six patients were treated with seed implantation alone, whereas 24 patients were treated with a combination of brachytherapy and external beam radiotherapy. The minimal percentage of the dose received by 90% of the prostate gland (%D90), the percentage prostate volume receiving 100% of the prescribed minimal peripheral dose (V100), and the operation time were compared among every 10 consecutive patients. RESULTS: The means of %D90 and V100 were 109.6% and 93.4%, respectively. When compared with the first 10 patients, both D90 and V100 showed significant improvement in the following 10 consecutive patients. Similarly, the mean operation time decreased significantly according to the accumulated number of patients. CONCLUSIONS: Our initial experience with the first 100 cases suggests that LDR-brachytherapy needs accumulation of many more patients to obtain high-quality post-implant dosimetric outcomes.

Haga K, Tomioka A, Liao CP, Kimura T, Matsumoto H, Ohno I, Hermann K, Logg CR, Jiao J, Tanaka M, Hirao Y, Wu H, Kruse CA, Roy-Burman P, Kasahara N. · Department of Medicine, University of California-Los Angeles, California, USA. · J Urol. · Pubmed #19010487 No free full text.

Abstract: PURPOSE: Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer. MATERIALS AND METHODS: PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging. RESULTS: Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-gamma secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo. CONCLUSIONS: The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.

Tomioka A, Tanaka M, De Velasco MA, Anai S, Takada S, Kushibiki T, Tabata Y, Rosser CJ, Uemura H, Hirao Y. · Department of Urology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. · Mol Cancer Ther. · Pubmed #18644998 links to  free full text

Abstract: The tumor suppressor gene MMAC/PTEN located on chromosome10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study, we generated a new type of gene transfer drug, GelaTen, which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance.

Hinotsu S, Akaza H, Usami M, Ogawa O, Kagawa S, Kitamura T, Tsukamoto T, Naito S, Namiki M, Hirao Y, Murai M, Yamanaka H, Anonymous00019. · Urology and Andrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki prefecture, 305-8575, Japan. · Jpn J Clin Oncol. · Pubmed #17965423 links to  free full text

Abstract: BACKGROUND: Based on the data of current status of endocrine therapy for prostate cancer registered in the Japan Study Group of Prostate Cancer (J-CaP), we conducted an analysis of primary androgen deprivation therapy (PADT) and an interim analysis of the prognosis. METHODS: Of the 26 272 cases registered in the server of J-CaP, the 19 409 cases initially receiving PADT were included in this study. The initial therapy was divided into eight categories according to its features. RESULTS: Of the 19 409 patients, 1513 (7.8%) were given anti-androgen monotherapy, 955 patients (4.9%) surgical castration only, 1001 patients (5.2%) surgical castration + anti-androgen, 3015 patients (15.5%) LHRH monotherapy, 1658 patients (8.5%) LH-RH + short-term anti-androgen, 10 434 patients (53.8%) LH-RH + anti-androgen, 37 patients (0.2%) watchful waiting and 796 patients (4.1%) other therapy. In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage. CONCLUSIONS: The pattern of PADT is more typical in Japan compared with that in the United States. Patients who received MAB accounted for 59.0% of all the patients. MAB tends to be more often selected for patients who are rated as being at high risk on the basis of high Gleason score or PSA level upon diagnosis in each clinical stage of the disease. Investigations of the outcome are on-going and they will make clear the significance of this trend in Japan.

Matsumura Y, Otani T, Yoneda T, Matsumoto Y, Maruyama Y, Fujimoto K, Hirao Y. · Department of Urology, Matsusaka Chuo General Hospital, Japan. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #17929458 No free full text.

Abstract: PURPOSE: Staging for prostate cancer often includes computed tomography (CT) and bone scan in Japan. We examined the criteria of avoiding unnecessary CT and bone scan for the prostate cancer patients at Matsusaka Chuo General Hospital. SUBJECTS AND METHODS: 211 patients were newly diagnosed at our institution between 1998 September and 2004 April. We reviewed data from 208 patients who had a staging CT and bone scan. The data was analysed using Gleason score, clinical T-stage and serum prostatic specific antigen (PSA) level. RESULTS: CT detected lymphadenopathy in 19 patients (9.1%), Bone scan detected bone metastasis in 31 patients (14.9%). However there was no lymphadenopathy detected by CT in the patients with 20 ng/ml or less. In the analysis using PSA and Gleason score, there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and Gleason sum 7 or less. In the analysis using PSA and clinical local stage there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and localized lesion (cT1-2). CONCLUSION: In a new proatate cancer patient CT and bone scan can be avoidable by PSA level of 20 ng/ml or less and cT1-2 or less and Gleason sum 7 or less.