Prostatic Neoplasms: Akaza H

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.

This publication has no abstract.

Akaza H. · Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan. · Best Pract Res Clin Endocrinol Metab. · Pubmed #18471787 No free full text.

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

Akaza H. · Department of Urology, University of Tsukuba, Ibaraki, Japan. · BJU Int. · Pubmed #17229161 No free full text.

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

Mizokami A, Ueno S, Fukagai T, Ito K, Ehara H, Kinbara H, Origasa H, Usami M, Namiki M, Akaza H. · Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Japan. · BJU Int. · Pubmed #17229160 No free full text.

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

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.

Cheng C, Akaza H, Chen KK, Moore MA, Naito S, Song JM, Umbas R, Xia S, Anonymous00319. · UICC Asia Regional Office. · Asian Pac J Cancer Prev. · Pubmed #17059324 No free full text.

Abstract: Cancer of the prostate remains at relatively low incidence in Asia but rates are increasing rapidly in some countries and specific populations so that measures for control need our attention. Little is known about risk factors, although vegetables and phytoestrogens may be protective and fat, meat and dairy products may increase the risk. Physical exercise may have preventive effects, while tobacco and alcohol appear to have no consistent relationship. The lack of clear lifestyle targets means that emphasis needs to be placed on screening for various prostate specific antigen parameters and clinical treatment, whether hormonal, radio or surgical, alone or in combination. While there is a massive literature for the Western world, the limited literature available for Asia means that cooperation to obtain a standardized data base is a high priority if the most effective measures for the specific populations of Asian countries are to be identified and put into practice.

Akaza H. · Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba, Japan. · Gan To Kagaku Ryoho. · Pubmed #16898009 No free full text.

Abstract: 5-FU is a major anti-tumor agent, and many clinical trials have been conducted to determine the efficacy of 5-FU and fluoropyrimidine derivatives for the treatment of urological cancers. S-1 is an oral fluoropyrimidine derivative that should be tested to demonstrate clinical efficacy for the treatment of urological cancers. Two phase II trials are being conducted to evaluate the efficacy and safety of S-1 as a single agent therapy for patients with hormone-refractory prostate cancer (HRPC) and renal cell carcinoma (RCC).

Akaza H. · Urology and Andrology, Functional and Regulatory Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan. · Cancer Sci. · Pubmed #16630114 No free full text.

Abstract: It has been conventionally accepted that primary androgen depletion therapy (PADT) is effective only as a palliative treatment against localized prostate cancer (LPC) and locally advanced prostate cancer (LAPC), like its effect against advanced (metastatic) prostate cancer. In Japan, however, PADT has long been the treatment of choice for LPC and LAPC. The frequency of PADT being chosen to treat LPC and LAPC is also on the rise in clinical practice in the USA. Very little evidence to support this trend has so far been available. A study on the outcomes of endocrine therapy is currently being conducted in Japan by the Japanese Prostate Cancer Surveillance Group. Results of several domestic and overseas randomized trials have recently been published, and evidence for the efficacy of PADT in LPC and LAPC has been accumulating. The effectiveness of PADT in LAPC, in particular, is worthy of attention. There is a possibility that therapeutic strategies for LPC and LAPC may change dramatically in the near future.

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.

Klotz L, Payne H, Gillatt D, Keane T, Morris C, Akaza H, Hirao, Akakura K, Fukagai T. · No affiliation provided · Gan To Kagaku Ryoho. · Pubmed #15934164 No free full text.

This publication has no abstract.

Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. · Can J Urol. · Pubmed #15780172 No free full text.

Abstract: Two decades have passed since the concept of Maximal Androgen Blockade (MAB) was first applied to the clinical treatment of prostate cancer. The theory is that by cutting off the supply of androgen from the adrenal gland, androgen blockade of the prostate could be made more complete. However, to date the clinical benefit of MAB has failed to live up to the theoretically expected effect. Having said that, fundamental research and clinical trials in recent years do indicate that the benefit of MAB is not merely an illusion.

Akaza H. · Department of Urology, Graduate University of Tsukuba. · Nippon Rinsho. · Pubmed #15714972 No free full text.

Abstract: Prostate cancers which are diagnosed during PSA screening include a significant number of clinically insignificant cancers. Useful strategy for needle biopsy is warranted. In addition, useful strategy for the timing of radical therapy for localized prostate cancer is warranted to be established. These strategies are essential to avoid over-diagnosis and over-treatment.

Akaza H. · Department of Urology, University of Tsukuba, Tsukuba-city, Ibaraki, Japan. · BJU Int. · Pubmed #15521883 No free full text.

This publication has no abstract.

Shimazui T, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. · Gan To Kagaku Ryoho. · Pubmed #15272577 No free full text.

Abstract: In order to reconfirm their diagnostic and predictive significance, bio- and molecular-markers of urological cancers (prostate, urothelial, kidney, and testicular cancer) are reviewed. In prostate cancer, although prostatic specific antigen (PSA) is a gold standard marker for its screening and monitoring, recent studies have revealed that PSA-related markers have additional information for patients with a gray zone PSA score. Prostate-specific membrane antigen (PSMA) may provide new applications for detection of high-grade cancer or microscopic circulating prostate cancer cells in the blood. In urothelial cancers, several urinary markers are available and may be helpful in the diagnosis of lower-grade urothelial cancers, which have a low sensitivity of urinary cytology. In testicular cancer, lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) are essential markers not only to determine the tumor stage but also the prognosis of the patient. In renal cell carcinoma (RCC), unfortunately, no definitive biomarker is available for its diagnosis and monitoring. Thus, we must find new specific bio- and molecular-markers that reflect the biological activity of RCC.

Akaza H, Nakagawa M, Tsuruo T, Saijo N, Sone S, Yamamoto N, Kakeji Y, Nakamura S, Kurebayashi J, Isonishi S, Ohashi Y, Blackledge G, Carmichael J. · Dept. of Urology, University of Tsukuba. · Gan To Kagaku Ryoho. · Pubmed #15114718 No free full text.

Abstract: Based on presentations on the basic concepts and scientific rationale of anti-angiogenic approaches to cancer therapy and the possible applications in the area of prostate cancer, gastrointestinal cancer, lung cancer and breast cancer it is easy to conclude that development of anti-angiogenic approaches into clinical therapies is extremely challenging. It is now well established that cancer growth is increased by angiogenic factors and that inhibition of angiogenesis decreases growth and metastatic potential. Anti-angiogenic effect can be obtained through interference with multiple targets. Further development of new strategies involving such novel cancer therapies requires wide reaching development of translational research abilities. However, for moving new therapies into the clinic same rigorous criteria need to be applied as is done for traditional therapies. Angiogenesis appear to be a critical factor for development of prostate, gastric, lung and breast cancers. Development of new anti-angiogenic treatment modalities might become very important in these diseases. A critical requirement for the successful clinical development will be the development of imaging techniques that can help evaluate the effect on blood vessel functionality. Such surrogate markers of anti-angiogenic effect will be essential for optimising molecules and doses.

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.

Akaza H, Ichikawa T, Tsuruo T, Shimada Y, Moriwaki H, Mori M, Noguchi S, Nakamura S, Saijo N, Sone S, Isonishi S, Ohashi Y, Hinotsu S, von Euler M, Blackedge G. · Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba. · Gan To Kagaku Ryoho. · Pubmed #14750337 No free full text.

Abstract: Based on reviews of the concept of diagnostics and in general and in specific tumour areas it was clear that development of diagnostic procedures involving genomics will allow for much better targeted and tailored treatments in the future. This will result in better efficacy and better tolerability of cancer treatments, but will also allow for progress in prediction, diagnosis and dose selection. Large collaborative projects studying the efficacy and safety of drugs on the genome level is promising to bring important benefits to both patients and the national economy by reducing useless drug therapy. In colorectal cancer there are several genetic defects identified that can act as the target for directed therapy in the future. Expressions of tumour specific antigens open the way for immunological targeted therapies. Developments in the understanding of the genomic basis for resistance to anti-tumour therapy is promising to help targeting patients likely to respond and not develop resistance. A Japanese model is being developed to determine the relative risk of breast cancer of Japanese women. Based on this prevention therapies can be instigated. The last four years have seen the introduction of four novel targeted therapies. If this model should become a standard in the future, much stronger collaboration between academic research and pharmaceutical industry need to develop.

Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Japan. · BJU Int. · Pubmed #14678365 No free full text.

Abstract: This article reviews the clinical disease-free survival (DFS) and disease-related mortality (DRM) data from published prospective, randomized trials of goserelin, given alone as adjuvant treatment or combined with a nonsteroidal antiandrogen as neoadjuvant treatment in patients with locally advanced or localized prostate cancer. Four trials were of radiotherapy and one of radical prostatectomy. The five trials included > 3500 patients and the median follow-up was 4.8-7.1 years. There were statistically significant improvements in clinical DFS with goserelin support relative to the control treatment in all five trials (each log-rank P </= 0.004). Reductions in the risk of DRM were statistically significant with adjuvant goserelin vs no adjuvant treatment to support radiotherapy in one trial, and with adjuvant goserelin or bilateral orchidectomy vs no adjuvant treatment to support radical prostatectomy in another (each log-rank P </= 0.001). Time-point estimates of the rates of clinical DFS and DRM were in favour of goserelin support vs control in all five trials at 5 years and in the three trials for which data were available at 8 years. Goserelin support therefore improves clinical DFS and reduces DRM after radiotherapy or radical prostatectomy. Adjuvant goserelin may offer greater clinical benefits than neoadjuvant hormonal treatment.

Miyanaga N, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba. · Nippon Rinsho. · Pubmed #12599567 No free full text.

This publication has no abstract.

Hinotsu S, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. · Gan To Kagaku Ryoho. · Pubmed #12355941 No free full text.

Abstract: We reviewed comparative clinical studies for prostate cancer and bladder cancer performed in Japan. A systematic search was done using PubMed and Icyushi WEB to find randomized clinical trials and the result was verified. Each manuscript was summarized according to the seven items of stage, entry period, exposure, endpoint, sample size, method of randomization and result. Forty reports were found as randomized clinical trials for prostate cancer, and sixty-two reports were identified for bladder cancer. Most exposures for advanced prostate cancer were hormonal therapy involving intravesical instillation after transurethral resection for superficial bladder cancer. At minimum, we have clarified that large scale randomized trials have been conducted in Japan for both prostate cancer and bladder cancer.

Miyanaga N, Tsukamoto S, Hattori K, Kawai K, Shimazui T, Uchida K, Akaza H. · Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba. · Gan To Kagaku Ryoho. · Pubmed #12040674 No free full text.

Abstract: Prostate cancer, bladder cancer, renal cancer and testicular cancer are common among urological cancers. The treatment strategy for testicular cancer using chemotherapy has been well established and has been shown to be successful. Chemotherapy and radiotherapy play important roles in multidisciplinary therapy for bladder cancer. Radiotherapy is often used as a radical treatment that is practically equivalent to surgery for prostate cancer. In addition, radiotherapy is useful in cases of bone or brain metastases. In the field of chemotherapy, the development of new agents that would make breakthroughs similar to that of cisplatin is awaited. Taxanes and gemcitabine are good candidates. In the field of radiotherapy, 3D conformal radiation therapy (CRT), which has excellent beam distribution, has recently come into wide use. Moreover, brachytherapy and proton and ion beam therapy are expected to prove useful in prostate cancer therapy.

Kawai K, Tani K, Asano S, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. · Mol Urol. · Pubmed #12006240 No free full text.

Abstract: There is no standard effective therapy for metastatic renal-cell carcinoma (RCC) or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted to a tumor-associated antigen may be effective. Transduction of the gene encoding granulocyte-macrophage colony-stimulating factor has shown promise in preclinical studies, and clinical trials are in their early stages. Both autologous cancer cells and partially HLA-matched allogenic cells are being studied. No dose-limiting side effects have been observed, and a few patients have had transient objective tumor regressions. Further trials with more frequent and, probably, longer immunization schedules are needed to define efficacy.

Lieberman R, Bermejo C, Akaza H, Greenwald P, Fair W, Thompson I. · Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA · Urology. · Pubmed #11744441 No free full text.

This publication has no abstract.

Uchida K, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan. · Gan To Kagaku Ryoho. · Pubmed #11681260 No free full text.

Abstract: Prostate specific antigen (PSA) has been widely used as a tumor marker for screening, diagnosis and monitoring of prostate cancer. Use of PSA is very important for diagnosis during the primary screening for the early detection of prostate cancer. The presence of various PSA assays and with no uniform serum data have led to confusion among clinicians in the evaluation of serum data. The characteristics of each PSA assay, such as the equimolar or skewed type, must be taken into consideration at the time of use. For the early detection of prostate cancer, PSA density (PSAD), PSA adjusted for the transiton zone volume (PSATZ) and free to total PSA ratio may be useful in the selection of patients with intermediate PSA levels who should undergo prostate needle biopsy.

Tsukamoto S, Akaza H. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. · Gan To Kagaku Ryoho. · Pubmed #11478140 No free full text.

Abstract: We offer a historical overview of endocrine therapy for prostate cancer. Hormone therapy remains the cornerstone of treatment for patients with locally advanced or metastatic prostate cancer. Although this therapy has been traditionally performed by oral estrogen or bilateral orchiectomy, there are now two most important pharmacological hormonal therapies: LH-RH agonist and antiandrogen therapy. We do not have yet sufficient data to conclude whether maximal androgen blockade from the combined use of an LH-RH agonist and an antiandrogen will prolong the survival in patients with metastatic prostate cancer, nor to conclude whether neoadjuvant androgen ablation therapy improves the disease-free survival of patients after radical prostatectomy. New treatment strategies and modalities such as LH-RH antagonists, intermittent hormonal therapy, and antiandrogen monotherapy are appearing and being tested in clinical trials. However, to date there is still no effective therapy for patients who have hormone refractory disease.