Prostatic Neoplasms: Ito K

Ito K, Kakehi Y, Naito S, Okuyama A, Anonymous00017. · Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. · Int J Urol. · Pubmed #18786203 No free full text.

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

Ito K. · No affiliation provided · Eur Urol. · Pubmed #17849514 No free full text.

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Ito K, Schrder FH. · No affiliation provided · Urology. · Pubmed #12559259 No free full text.

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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.

Suzuki K, Ito K. · Department of Urology, Gunma University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15714975 No free full text.

Abstract: Multiple core prostate biopsy was introduced by Eskew et al in 1995, and many procedures of multiple core biopsy were proposed. These methods showed importance of taking samples from lateral part of peripheral zone, transition zone or apex. Cancer detection rates were dramatically increased in comparison with those detected by traditional systematic sextant biopsy (SSB). Utilization of the template, age-volume adjusted parameter or apical horn biopsy facilitated the efficacy of multiple core biopsy. Furthermore, these techniques could contribute to accurate estimation of pathological findings. Multiple core prostate biopsy would get to be more important in modern prostate specific antigen era when more T1c or more early stage prostate cancer would be detected.

Ito K. · Department of Urology, Gunma University Graduate School of Medicine Maebashi, 371-8511. · Rinsho Byori. · Pubmed #15344561 No free full text.

Abstract: As the most frequently diagnosed cancer and the second leading cause of cancer death in most Western countries, prostate cancer represents a significant health care problem. The introduction of routine prostate-specific antigen (PSA) screening for asymptomatic men is still controversial. To solve uncertainties regarding the screening for prostate cancer, prospective randomized controlled trials are ongoing in the USA and Europe. The development of an optimal screening system may be one of the most important issues for screening for prostate cancer, and it should be set not only for reducing the mortality rate of prostate cancer, but also for reducing the cost. The best screening modality for the 1st step of mass screening for prostate cancer is the PSA test. Furthermore, the cut-off value should be set in an age-specific manner. The risk of developing prostate cancer in men with PSA levels of 4.0 ng/ml or lower increases when the baseline PSA levels are higher. Therefore, re-screening for men without suspicious findings for prostate cancer at the 1st step of screening should be set relative to the baseline PSA and digital rectal examination status. In the 2nd step of screening, the PSA density adjusted by the transition zone volume (PSATZD) and free/total PSA ratio (%f-PSA) may be useful in the selecting patients who should be biopsied. The optimal cut-offs for PSATZD and %f-PSA have not been confirmed, however, and an age-adjusted setting should be considered to detect clinically significant cancer. The method of prostate biopsy is also very important for improving the diagnostic accuracy for prostate cancer. The number of biopsy cores should be set relative to prostate volume. Furthermore, the clinically significant tumor volume may be smaller in younger men than in older men. Therefore, the optimal number of biopsy cores should be set according to age and prostate volume. Both an optimal screening system and minimally invasive treatments will be available in the future, and screening for prostate cancer may be more useful for elderly males.

Ito K, Yamamoto T, Kubota Y, Yamanaka H. · Department of Urology, Gunma University School of Medicine. · Nippon Rinsho. · Pubmed #11022750 No free full text.

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Shiono A, Kurokawa K, Ito K, Yamanaka H. · Department of Urology, Gunma University School of Medicine. · Nippon Rinsho. · Pubmed #11022732 No free full text.

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Yamanaka H, Ito K, Naito S, Tsukamoto T, Usami M, Fujimoto H, Matsuoka N, Fukui I, Harada M, Ohashi Y, Kotake T, Kakizoe T. · Institute for Preventive Medicine, Kurosawa Hospital, Takasaki, Japan. · Prostate. · Pubmed #15468166 No free full text.

Abstract: PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Koiso K, Yamanaka H, Ito K, Yoshinaka R, Uchida S, Yokokawa K. · Senpo Tokyo Takanawa Hospital. · Hinyokika Kiyo. · Pubmed #12613015 No free full text.

Abstract: TAP-144-SR (3M) is a 3-month sustained releasing injection of a super-active agonist of luteinizing hormone releasing hormone (LH-RH), leuprorelin acetate. At the Department of Urology of Gunma University Hospital, TAP-144-SR (3M) was injected once subcutaneously into 10 prostatic cancer patients who had had no treatment in the past to investigate safety, serum testosterone levels, drug concentrations and efficacy. In safety, no problematic adverse reactions occurred, and the drug was well tolerated. Serum testosterone levels elevated temporarily up to 2 days after injection and then were reduced rapidly. The levels were reduced below the castration level (100 ng/dl) after 3 weeks and then remained reduced up to 12 weeks. Serum TAP-144 levels including metabolite M-I, elevated to maximal plasma concentration up to 3 hours after injection and then were maintained at about 0.2 ng/ml between 1 week and 12 weeks after injection. With respect to the anti-tumor effects, the response rate according to "criteria of prostate cancer" at 12 weeks after injection was 100% (stable response cases) and the ratio of PSA normalization at 12 weeks was 90%. These results showed that an injection of TAP-144-SR (3M) was well tolerated in prostate cancer patients having no prior treatment and inhibited serum testosterone persisting for at least 12 weeks so that TAP-144-SR (3M) was concluded to be safe and clinically effective for prostate cancer patients.

Nakazato H, Suzuki K, Ito K, Fukabori Y, Kurokawa K, Yamanaka H. · Department of Urology, Gunma University School of Medicine. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #11235144 No free full text.

Abstract: PURPOSE AND METHODS: We investigated the influence of flutamide on plasma adrenal androgens in advanced prostate cancer patients treated with dietylstilbestrol diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist (LH-RH agonist). Nine patients were enrolled in this study and they were divided into the following two treatment groups; group A: LHRH agonist mono-therapy (n = 4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up, all patients were treated with DES-DP. RESULTS: Two-week DES-DP administration led to reduction of plasma adrenal androgen levels. These levels were kept lower for 16 weeks in group B in contrast with group A in which the levels returned to the pretreatment levels. Basal ACTH levels in group B were significantly lower than those in group A. CONCLUSION: From our observations, we found that flutamide reduced adrenal androgen levels in prostate cancer patients treated with LH-RH agonist. ACTH suppression might be related to this phenomenon.

Tamada T, Sone T, Jo Y, Toshimitsu S, Yamashita T, Yamamoto A, Tanimoto D, Ito K. · Department of Radiology, Kawasaki Medical School, Okayama, Japan. · J Magn Reson Imaging. · Pubmed #18777532 No free full text.

Abstract: PURPOSE: To investigate the utility of apparent diffusion coefficient (ADC) values for discriminating tumor in patients with prostate cancer from normal prostatic tissues in healthy adult men, and to identify correlations between ADC and histologic grade of prostate cancer. MATERIALS AND METHODS: A total of 125 healthy male volunteers (mean age, 60 years; range, 50-86 years) and 90 prostate cancer patients (mean age, 71 years; range, 51-88 years) underwent diffusion-weighted imaging (DWI) of the prostate with a single-shot echo-planar imaging sequence using b-factors of 0 and 800 sec/mm2. ADC was measured from two locations in the peripheral zone (PZ) and two locations in the central gland (CG) in normal subjects, and tumor locations of PZ or transition zone (TZ) in patients with prostate cancer. RESULTS: Mean ADC values of tumor regions in both PZ (1.02+/-0.25x10(-3) mm2/sec) and TZ (0.94+/-0.21x10(-3) mm2/sec) were significantly lower than those in the corresponding normal regions (1.80+/-0.27x10(-3) mm2/sec and 1.34+/-0.14x10(-3) mm2/sec, respectively) (P<0.0001 each). Furthermore, a significant negative correlation was identified between ADC in PZ cancer and tumor Gleason score (rho=-0.497, P<0.0001). CONCLUSION: ADC values appear to provide acceptable diagnostic accuracy in both PZ and TZ.

Ohi M, Ito K, Yamamoto T, Miyakubo M, Takechi H, Kubota Y, Suzuki K. · Department of Urology, Graduate School of Medicine, Gunma University Graduate School, Maebashi, Japan. · Urology. · Pubmed #18455775 No free full text.

Abstract: OBJECTIVES: According to epidemiologic surveys, the number of deaths from prostate cancer in Japanese men increased rapidly from 1970 to 2006. However, it is difficult to know the real incidence of, and mortality due to, prostate cancer because the reliability of death certificates and the cancer registry system in Japan are poor. Recently, several studies have demonstrated that baseline prostate-specific antigen (PSA) levels could be one of the most important predictive factors for developing prostate cancer. Therefore, we hypothesized that changes in the baseline PSA distribution in the screening population could reflect trends in the true incidence rate of prostate cancer. METHODS: From 1988 to 2003, 32,274 men, aged 50-79 years, participated in population-based screening for prostate cancer for the first time in Gunma Prefecture, Japan. Changes in the baseline PSA distributions, stratified by a 5-year age range and calendar year, were investigated. The relationships between age and log(10) PSA levels were also investigated and stratified by calendar year. RESULTS: The median baseline PSA level was 0.9-1.2 ng/mL and had not recently increased. No specific trends were found in the percentages of participants with a PSA level greater than 2.0, 4.0, or 10.0 ng/mL within the same age range during the 16-year period. CONCLUSIONS: The increase in the incidence of, and mortality rates for, prostate cancer demonstrated by epidemiologic research might have been misleading in Japan. Investigational changes in the baseline prostate-specific antigen (PSA) distribution of the screened populations revealed that the true incidence rate of prostate cancer in Japan might have been almost the same during the past 16 years.

Otsuki H, Sumitomo M, Umeda S, Shirotake S, Tobe M, Ito K, Asano T, Nagakura K, Hayakawa M. · Department of Urology, National Defense Medical College Hospital. · Hinyokika Kiyo. · Pubmed #18411774 No free full text.

Abstract: We studied the impact of combined transurethral resection of the prostate (TURP) and high intensity focused ultrasound (HIFU) for localized prostate cancer (CaP) to decrease side effects such as prolonged urinary voiding disturbance observed after HIFU treatment. Included in this study were 18 patients with clinically localized CaP indicated for HIFU just followed by TURP (TUR combination group). Complete response was defined in accordance with ASTRO consensus statement and negative sample in biopsies performed 6 months after the HIFU treatment. Prostate specific antigen (PSA) nadir, International Prostate Symptom Score (IPSS) and morbidity during follow-up of TUR combination group were compared with those of a control of 18 patients who took HIFU treatment alone (HIFU monotherapy group). No statistical significances on the values of preoperative parameters (PSA, prostate volume, Gleason score, and IPSS) between these two groups. The median follow-up duration was 10 (5-15) months in both groups. A statistically significant impact was observed between TUR combination group and HIFU monotherapy group on median catheter time (5 versus 13 days, P<0.0001), PSA nadir (0.096 ng/ml versus 0.430 ng/ml in median, P<0.05) and the evolution of the post-treatment IPSS (8 versus 13.5 in median, P<0.0003) at 3 months after treatment. Urethral stricture necessary for urethral dilation was noted in 1 patient (5.6%) in the TUR combination group while in 2 (11.1%) in the HIFU monotherapy group. CR was obtained in 88.9% in the TUR combination group and 83.3% in the HIFU monotherapy group. Our study suggests that the combination of TURP with HIFU treatment improves posttreatment urinary status without additional morbidity.

Yamamoto T, Ito K, Miyakubo M, Takechi H, Suzuki K, Akimoto T, Ishikawa H, Nakano T. · Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. · Urology. · Pubmed #18372027 No free full text.

Abstract: OBJECTIVES: To propose a "nomogram ranking" that gives an objective assessment of any treatment strategy from various institutions. It is difficult to objectively compare treatment outcomes for patients with prostate cancer among institutions because of the large differences in the clinicopathologic backgrounds and treatment strategies. METHODS: From January 2001 to September 2005, 71 consecutive patients with locally advanced prostate cancer were treated with external beam radiotherapy (EBRT) and subsequent high-dose rate brachytherapy combined with long-term hormonal therapy. The 5-year prostate-specific antigen relapse-free survival (PFS) rates were calculated by Kaplan-Meier analysis for all patients and also for subdivided patients according to prostate-specific antigen range or Gleason score. Also, the 5-year PFS rates were estimated by Kattan nomogram, assuming that all 71 patients were treated with 72 Gy of EBRT or EBRT plus neoadjuvant hormonal therapy. The estimated PFS rates were ranked in order from worse to better outcomes (nomogram ranking). The 5-year PFS rates estimated by Kaplan-Meier analysis assessed the position within the nomogram ranking. RESULTS: The 5-year PFS rate estimated by Kaplan-Meier analysis for all 71 patients was 82.4%. The median 5-year PFS rate estimated by Kattan nomogram was 66%, assuming that all patients were treated with EBRT and neoadjuvant hormonal therapy. The actual 5-year PFS rate estimated by Kaplan-Meier analysis ranked 56 of 71 patients assumed to be treated with neoadjuvant hormonal therapy and EBRT. Subdivided analyses revealed that our treatment strategy might be advantageous for patients with a Gleason score of 7 or less, regardless of the prostate-specific antigen level. CONCLUSIONS: The nomogram ranking might be an objective and reliable assessment method of various treatment strategies for patients with prostate cancer.

Kono Y, Kubota K, Mitsumoto T, Tanaka A, Ishibashi A, Kobayashi K, Ito K, Itami J, Kanemura M, Minowada S. · Division of Nuclear Medicine, International Medical Center of Japan, Tokyo, Japan. · J Nucl Med. · Pubmed #18344427 links to  free full text

Abstract: The purpose of this investigation was to monitor the localization and migration of 125I seeds after permanent brachytherapy for prostate cancer using a new scintigraphic technique that may overcome the drawbacks of conventional x-ray methods. METHODS: 125I seeds emit gamma-rays with an average energy peak of 28 keV. We used a gamma-camera equipped with low-energy high-resolution collimators that were tuned to an energy level of 35 keV with a 70% window width. Sixteen patients with prostate cancer were examined after 125I seed insertion. The number of seeds remaining in the prostate was confirmed using pelvic CT for postoperative dose planning; however, seeds that had migrated outside the prostate could not be detected. Furthermore, the migrated seeds were not completely traceable using chest or abdominal radiography. Thus, we adopted a scintigraphic technique to perform this task. The evaluation of radiography and scintigraphy findings was masked, and the rates of migrated seed detection were statistically examined using the McNemar test. To localize the migrated seeds, we fused the scintigraphic images of the migrated seeds and the patients' contours. RESULTS: Scintigraphy was successfully used to detect 20 migrated seeds of a total of 1,182 implanted seeds, whereas radiography was successfully used to detect 7. The sensitivity of the scintigraphy results was 20 of 20 (100%), whereas that of the radiography results was 7 of 20 (35%). Seed migration was detected in 11 of 16 patients (69%) using scintigraphy, whereas seed migration was detected in only 4 patients (25%) using radiography; this difference was statistically significant (P = 0.016). CONCLUSION: Scintigraphy is more effective for detecting seed migration and monitoring the localization of 125I seeds than radiography. The precise anatomic location of migrated seeds can be pinpointed using fusion images. Scintigraphy may become a standard procedure for monitoring seed migration during 125I brachytherapy in patients with prostate cancer.

Takechi H, Ito K, Yamamoto T, Miyakubo M, Ohi M, Suzuki K. · Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. · Urology. · Pubmed #18342926 No free full text.

Abstract: OBJECTIVES: It would be of value to compare the features of prostate cancer detected in various screening series around the world. Recently, some studies have demonstrated the value of pretreatment prostate-specific antigen (PSA) kinetics in predicting the outcome of radical prostatectomy and radiotherapy for men with localized prostate cancer. Therefore, the distribution of PSA velocity (PSAV) or PSA doubling time in screen-detected prostate cancer might be objective parameters to investigate how well each national screening system is working. METHODS: From 1992 to 2004, 957 men with prostate cancer were detected by screening in Gunma Prefecture, Japan. Of those, 275 men (29%) detected with consecutive screening tests participated in the present study. The PSAV was calculated by the PSA change between the most recent screening test and cancer diagnosis and also by linear regression analysis. The PSA doubling time was also calculated for 146 men who underwent screening at least three times. RESULTS: The median PSAV was 1.3 ng/mL/yr in those with Stage T1cN0M, 1.1 ng/mL/yr in those with T2N0M0, and 2.1 ng/mL/yr in those with T3N0M0. The percentage of men with a PSAV (linear regression analysis) greater than 2.0 ng/mL/yr was 13%, 12%, and 49% in men with clinical Stage T1cN0M0, T2N0M0, and T3N0M0, respectively. The median PSA doubling time was 57.1, 51.7, and 28.0 months for those with T1cN0M0, T2N0M0, and T3N0M0, respectively. CONCLUSIONS: Patients with prostate cancer with aggressive features are still detected in the population-based screening system in Japan. Even in Japan, where PSA screening is perhaps the most widespread among Asian countries, the screening system might be still immature compared with the systems in the United States and Western Europe.

Mikami H, Ito K, Yoshii H, Kosaka T, Miyajima A, Kaji T, Asano T, Hayakawa M. · Department of Urology, National Defense Medical College. · Hinyokika Kiyo. · Pubmed #18260356 No free full text.

Abstract: A 68-year-old male visited our division with an elevation of PSA level. He underwent a needle biopsy of the prostate, and the histopathological diagnosis was poorly differentiated adenocarcinoma (Gleason score 4+3). The cancer was clinically diagnosed as T2aN0M0, and he underwent extraperitoneal laparoscopic radical prostatectomy and bilateral pelvic lymphadenectomy. Cystography 14 days after the operation still showed leakage at the vesico-urethral anastomosis and a dumbbell shaped bladder. A few days later, prominence of lower abdomen and a slight swelling of right leg presented with a high fever. Computed tomography revealed a giant lymphocele in the retroperitoneal space. We percutaneously punctured the lymphocele by using ultrasonography, inserted a pigtail catheter, and drained 1,000 ml of lymphatic fluid. After the puncture, sclerotherapy with minocycline was performed four times. Twenty days after the puncture, the lymphocele cavity was found to have shrunken and the pigtail catheter was removed. The lymphocele was diminished and did not recur thereafter.

Ito K, Yamamoto T, Miyakubo M, Takechi H, Ohi M, Shibata Y, Suzuki K. · Department of Urology, Gunma University School of Medicine, Maebashi, Japan. · J Urol. · Pubmed #17698107 No free full text.

Abstract: PURPOSE: We clarified that lead time bias in screen detected prostate cancer is important for evaluating the outcome of any individual screening system. MATERIALS AND METHODS: Between 1992 and 2001, 195 and 958 prostate cancer cases with clinical T1c/T2N0M0 and T3N0M0 disease were enrolled in the current study as screen detected and outpatient clinic detected prostate cancer, respectively. Log10 prostate specific antigen velocity was calculated using log10 prostate specific antigen at diagnosis and at the most recent screening before cancer detection. Lead time in screen detected cancer was then estimated as the year when log10 prostate specific antigen in screen detected cancer would increase to the levels of log10 prostate specific antigen in outpatient clinic detected prostate cancer. RESULTS: Median log10 prostate specific antigen was 0.87 and 1.08 ng/ml for clinical T1c/T2N0M0 disease, and 1.14 and 1.53 ng/ml for T3N0M0 disease in screen and outpatient clinic detected cancer, respectively. The 25th, 50th and 75th percentiles of log10 prostate specific antigen velocity before cancer detection in the screening population were 0.05, 0.08 and 0.14 for T1c/T2N0M0 disease, and 0.07, 0.13 and 0.21 for T3N0M0 disease, respectively. The 25th, 50th and 75th percentiles of expected lead time in screen detected cancer were 1.9, 3.3 and 5.2 years for T1c/T2N0M0 disease and 1.4, 2.2 and 4.1 years for T3N0M0 disease, respectively. CONCLUSIONS: The lead time of screen detected cancer in our screening system is not as long as previously thought. This new methodology for lead time estimation may be useful for evaluating treatment outcomes of screen detected prostate cancer in individual screening systems done in various regions worldwide.

Sekine Y, Ito K, Yamamoto T, Nakazato H, Shibata Y, Hatori M, Suzuki K. · Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma-pref 371-8511, Japan. · Cancer Detect Prev. · Pubmed #17418977 No free full text.

Abstract: BACKGROUND: Many studies have shown the relationship between pretreatment serum testosterone levels and the clinical stage or histological grade, but the clinical significance of pretreatment testosterone levels is controversial. We studied the association of pretreatment total testosterone levels with the clinical stage and histological grade of prostate cancer. METHODS: We evaluated 2914 patients whose pretreatment testosterone levels were recorded from 1982 to 2002. Serum testosterone levels were measured by radioimmunoassay. RESULTS: There was a trend toward decreasing testosterone values with worsening clinical staging. There was a trend toward decreasing testosterone values with worsening histological grading, too. Patients with poorly differentiated adenocarcinoma had significantly lower testosterone levels than those with the others (versus well; p<0.01, moderately; p<0.01). CONCLUSIONS: Newly diagnosed patients with poorly differentiated adenocarcinoma of prostate have lower testosterone levels than the others.

Kobayashi T, Goto R, Ito K, Mitsumori K. · Department of Urology, Hamamatsu Rosai Hospital, Hamamatsu, Japan. · Eur J Surg Oncol. · Pubmed #17408910 No free full text.

Abstract: AIMS: To determine whether prostate cancer screening strategies with re-screening interval determined by individual baseline prostate-specific antigen values are cost-effective. METHODS: Based on the results of an actual contemporary screening program, we established Markov decision analytic models of prostate cancer screening with personalized re-screening interval strategies using cutoff baseline PSA levels for biennial screening as well as a model of uniformly annual or biennial screening. These strategies were compared in terms of cumulative incidence of early cancer and cost-effectiveness. RESULTS: Early cancer detection rates were similar among all strategies. Personalized strategies were more cost-effective compared to uniform screening strategies. If all participants with negative PSA results uniformly omit annual screening, it would be more costly but less effective (dominated). Contrary, annual screening for all participants would cost too much. These results were robust throughout sensitivity analysis incorporating every assumption in the models. CONCLUSIONS: This study adds important evidence that personalized rescreening strategies based on individual baseline PSA have advantages of cost-effectiveness against conventional uniform strategies.

Wadasaki K, Kaneyasu Y, Kenjo M, Matsuura K, Murakami Y, Hashimoto Y, Ito K, Kiriu H, Ito A. · Department of Radiology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. · Int J Clin Oncol. · Pubmed #17380439 No free full text.

Abstract: BACKGROUND: The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. METHODS: Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate +/- seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. RESULTS: The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. CONCLUSION: Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate +/- seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.

Miyamoto S, Ito K, Kurokawa K, Suzuki K, Suzuki K, Yamanaka H. · Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. · Int J Urol. · Pubmed #16834658 No free full text.

Abstract: BACKGROUND: Although Gleason grading may be the most useful system for evaluating biological activity of untreated prostate cancer, lack of interobserver validity with Gleason scores (GS) is an unsolved issue. In this study, the proliferating cell nuclear antigen labeling index (PCNA LI) in untreated prostate cancer was investigated in order to clarify the usefulness of supplemental and objective markers for evaluating the biologic features of prostate cancer. METHODS: Sixty cases of prostate cancer were randomly selected from the cancer registry in Gunma University Hospital for this study. PCNA LI were evaluated using paraffin-embedded biopsy cores taken at diagnosis. Correlation of PCNA LI with the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels and age were evaluated. Cumulative rates of freedom from cause-specific death were also evaluated stratified by various clinicopathologic features, including PCNA LI using Kaplan-Meier analysis. RESULTS: Proliferating cell nuclear antigen labeling index was significantly higher in patients with PSA levels over 100 ng/mL, advanced clinical stage (>T4, N1 or M1 disease), higher Gleason grade or with a higher GS than in those with other clinicopathologic features. The 5-year cumulative rate of death from prostate cancer was significantly higher at 62% in patients with a PCNA LI of 20 or more than those with PCNA LI of less than 20, who accounted for 4%. CONCLUSIONS: Proliferating cell nuclear antigen labeling index in combination with Gleason grading system may be of clinical value in evaluating biologic features and also in predicting cause specific survival of prostate cancer in an objective, reliable and reproducible manner.

Akimoto T, Katoh H, Noda SE, Ito K, Yamamoto T, Kashiwagi B, Nakano T. · Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. · Int J Radiat Oncol Biol Phys. · Pubmed #16168839 No free full text.

Abstract: PURPOSE: We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. METHODS AND MATERIALS: Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in the urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 42 patients (63%); Grade 2-3, 25 patients (37%). The urethral dose in HDR brachytherapy was determined using the following dose-volume histogram (DVH) parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. In addition, the D5 (dose covering 5% of the urethral volume), D10, D20, and D50 of the urethra were also estimated. The V30-V150 values in the patients with Grade 2-3 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. The D10 and D20, but not D5 and D50, values were also significantly higher in the patients with Grade 2-3 acute GU toxicity than in those with Grade 0-1 toxicity. Regarding the influence of the number of needles implanted, there was no correlation between the number of needles implanted and the severity of acute GU toxicity or the V30-V150 values and D5-D50 values. CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer, when considered from the viewpoint of acute toxicity. However, because the urethral dose was closely associated with the grade of severity of the acute GU toxicity, the urethral dose in HDR brachytherapy must be kept low to reduce the severity of acute GU toxicity.

Akimoto T, Ito K, Saitoh J, Noda SE, Harashima K, Sakurai H, Nakayama Y, Yamamoto T, Suzuki K, Nakano T, Niibe H. · Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. · Int J Radiat Oncol Biol Phys. · Pubmed #16168838 No free full text.

Abstract: PURPOSE: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. METHODS AND MATERIALS: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05). CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.