Prostatic Neoplasms: Baba S

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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Satoh T, Irie A, Egawa S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Curr Gene Ther. · Pubmed #15638715 No free full text.

Abstract: The incidence of prostate cancer has dramatically increased worldwide in the past decade, with mortality rates also increasing in many countries. Once prostate cancer is diagnosed, it is important to rapidly begin a treatment regimen that is either potentially curative or impedes disease progression. When the disease is confined to the prostate, it can be cured by radical prostatectomy or irradiation therapy. However, there are no curative therapies for locally advanced, recurrent, or metastatic diseases. Clearly, new therapies are needed for these patients. Gene therapy may provide additional therapeutic options with the potential to affect both localized and metastatic disease. Virus-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene transfer, followed by a course of the prodrug ganciclovir (GCV), so-called suicide gene therapy, has been demonstrated by several investigators. The present in situ gene therapy clinical trial for human prostate cancer demonstrated safety, clinical efficacy, and biological effects of antitumor activity. HSV-tk clinical trials for prostate cancer are also ongoing in Japan, the Netherlands, and Mexico. Currently, numerous preclinical studies have reported immunomodulatory cytokine gene therapy, such as interleukin-2, interleukin-12, B7-1 (CD80), B7-2 (CD86) and granulocyte-macrophage colony-stimulating factor. Several clinical studies have been approved that potentially will show that these immunomodulatory gene therapies may generate an effective local and systemic antitumor activity and that should provide options for patients with prostate cancer. We review the multiple issues involved in current in situ gene therapy (gene/immunotherapy), its outcome, and future directions for patients with prostate cancer.

Egawa S, Baba S. · Department of Urology, Kitasato University School of Medicine. · Nippon Rinsho. · Pubmed #12599586 No free full text.

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Ishiyama H, Satoh T, Kitano M, Tsumura H, Kotani S, Okusa H, Uemae M, Baba S, Hayakawa K. · Department of Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Japan. · Jpn J Clin Oncol. · Pubmed #18577509 links to  free full text

Abstract: OBJECTIVE: To report 4 year results obtained with our initial 100 patients with localized prostate cancer treated by interstitial permanent brachytherapy. METHODS: One-hundred Japanese men with clinically localized prostate cancer underwent interstitial permanent prostate brachytherapy using (125)I seeds. Median follow-up was 36 months (range, 30-42 months). Median initial prostate-specific antigen (PSA) level was 6.7 ng/ml (range, 1.5-25.2 ng/ml). Of these 100 patients, 31 received neoadjuvant hormone therapy for several months. Treatment morbidities were assessed using Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria. RESULTS: A mean of 95 seeds (range, 48-123 seeds) were successfully implanted in patients with prostate cancer. Mean prostate volume receiving at least 100% dose (V100) and dose to 90% of prostate volume (D90) for the 100 patients were 96.6% and 166.1 Gy, respectively. Urinary morbidity was common, but was usually not severe. Only four patients needed catheterization for urinary retention (Grade 3) during follow-up. Most patients displayed no rectal morbidity after implantation, with only 3% of patients showing RTOG Grade 2 rectal morbidity and no patients showing morbidity of Grade 3 or more. Three patients experienced biochemical failure according to Phoenix consensus definition during follow-up. One patient displayed clinical failure with lymph node recurrence. CONCLUSIONS: These results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer. The import of matured techniques developed in Western countries might allow bypass of the trial-and-error process in Japanese institutions.

Tabata K, Satoh T, Matsumoto K, Fujita T, Irie A, Iwamura M, Yanagisawa N, Matsuda D, Muramoto M, Kadowaki K, Suyama K, Shoji K, Koh H, Kawakami T, Okayasu I, Egawa S, Baba S. · Department of Urology, Kitasato University, School of Medicine. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #16898594 No free full text.

Abstract: PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

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.

Egawa S, Okusa H, Matsumoto K, Suyama K, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #12970730 No free full text.

Abstract: We conducted a study in order to characterize changes after withdrawal of androgen ablation (AA) for prostate cancer. AA was withdrawn in 38 Japanese patients with prostate cancer who had undergone this therapy for various periods. Patients were stratified into those who had undergone AA for less than 24 months (Group 1, n=12) and those with longer periods of AA (Group 2, n=26). Serial changes in hormones and prostate-specific antigen (PSA) were prospectively monitored following cessation of AA. The median durations of AA in the two groups were 8.5 and 54.5 months, respectively. Levels of total testosterone (T), luteinizing hormone and PSA increased significantly with time. At the end of 2 y, 30/38 patients (78.9%) had T levels above 50 ng/dl and 19/38 (50%) had levels above 320 ng/dl. Patients in Group 2 required significantly longer duration for T recovery. Complete T recovery is not always accompanied by rising PSA. Recovery of T levels is often slow following cessation of prolonged AA. Expression of PSA after AA is often variable and unpredictable. Thus, interpretation of outcomes in clinical trials incorporating AA needs caution and careful consideration.

Kuruma H, Fujita T, Shitara T, Egawa S, Yokoyama E, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #12941125 No free full text.

Abstract: BACKGROUND: Paclitaxel used in combination with estramustine has been shown to exert synergistic cytotoxicity in patients with hormone-refractory prostate cancer (HRPC). There have been few reports of this therapy in an Asian male population. METHODS: Nine patients with progressive metastatic HRPC completed at least one cycle of combination therapy employing weekly paclitaxel plus estramustine. Paclitaxel was given weekly for 3 weeks as a 2-h intravenous infusion at a dose of 100 mg/infusion. The cycle was repeated every 4 weeks. A dose of 280 mg of oral estramustine was administrated twice daily for 21 days from the first day of each cycle. Both efficacy and toxicity were recorded. RESULTS: Grade 1 sensory neuropathy was seen in three patients (33%) and grade 4 thrombopenia/anemia was seen in one patient (11%). Performance status improved in three of seven patients (43%), while six patients (67%) showed a 50% or greater decline in prostate-specific antigen levels. Two of these patients experienced significant improvement in bone pain. One patient died of cardiac infarction during this trial and another died of disseminated intravascular coagulopathy subsequent to gastrointestinal bleeding. An additional patient suffered non-fatal pulmonary infarction. The one-year median survival rate was 22.2% and the overall survival period was 36 weeks. CONCLUSION: Although weekly paclitaxel plus estramustine may pose a significant risk, this combination may have a beneficial effect on the quality of life HRPC patients. A well-designed phase I-II trial in an Asian male population is highly recommended.

Matsui Y, Egawa S, Tsukayama C, Terai A, Kuwao S, Baba S, Arai Y. · Department of Urology, Kurashiki Central Hospital, Okayama, Japan. · Jpn J Clin Oncol. · Pubmed #12578902 links to  free full text

Abstract: BACKGROUND: Although prostate cancer has been prevalent in Japan, there has been no particular model for predicting the pathological stage in the Japanese population. We examined whether artificial neural network analysis (ANNA), which is a relatively new diagnostic tool in prostate cancer, can be one of the predictive methods for predicting organ confinement, compared with the traditional logistic regression model, in the Japanese population for the first time. METHODS: The study population comprised 178 men who underwent radical prostatectomy at our institutions between October 1992 and May 1999. As additional pretreatment parameters to the preoperative serum PSA level, clinical TNM classification and biopsy Gleason score, the percentage of number of cores exhibiting traces of tumor, maximum tumor length in biopsy cores, PSA density and patient age were used. The predictive ability of ANNA with several parameters for a set of 36 randomly selected test data was compared with those of logistic regression analysis and 'Partin Tables' by area under the receiver operating characteristics (ROC) curve analysis. RESULTS: Of 178 patients, 97 (54.5%) had organ-confined disease but 81 (45.5%) had locally advanced disease. With three parameters, the area under the ROC curve of ANNA (0.825 +/- 0.071) was larger than those for logistic regression (0.782 +/- 0.079) and Partin Tables (0.756 +/- 0.087), but not to a significant extent (P = 0.690 and 0.541). Although the expansion of the parameters did not increase the difference in area under the ROC curve between the best ANNA and logistic regression (0.899 +/- 0.053 and 0.873 +/- 0.065, respectively), the difference between the best ANNA and Partin Tables did not reach but approached statistical significance (P = 0.157). CONCLUSION: Although more modeling optimization is necessary to improve the predictive accuracy and generalizability of ANNA, we suggest that there is the possibility for this new predictive method to evolve in the analysis of clinical staging of prostate cancer.

Uchida T, Sanghvi NT, Gardner TA, Koch MO, Ishii D, Minei S, Satoh T, Hyodo T, Irie A, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Urology. · Pubmed #11880077 No free full text.

Abstract: OBJECTIVES: To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue. METHODS: We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed. RESULTS: A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention. CONCLUSIONS: Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.

Egawa S, Suyama K, Arai Y, Tsukayama C, Matsumoto K, Kuwao S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #11389745 No free full text.

Abstract: BACKGROUND: North American investigators have suggested the usefulness of risk-group stratification based on prostate-specific antigen (PSA), clinical stage and biopsy Gleason score for predicting the biochemical outcome of prostate cancer after radical prostatectomy. There have been no reports of the application of this stratification to early biochemical outcome after radical surgery in Japanese men. METHODS: The study population consisted of 178 men treated with radical retropubic prostatectomy and bilateral pelvic lymph node dissection at Kitasato University Hospital (n = 110) and Kurashiki Central Hospital (n = 68) between October 1992 and May 1999. Pathologic and biochemical outcomes after radical prostatectomy were analyzed based on risk-group stratification. Risk groups were further analyzed according to detailed pathologic findings at biopsy. RESULTS: The median follow-up period for the 178 patients after radical surgery was 41.5 months (range, 2.0--82.0 months; mean, 40.9 months). Fifty-eight patients experienced PSA failure at a median of 8.0 months following surgery (range, 0.0--58.0). Risk-group stratification distinctly defined groups of pathologic findings in the radical prostatectomy specimens. The proportion of patients with PSA failure for low, intermediate and high-risk groups were 9.5%, 23.9% and 56.9%, respectively (P < 0.0001). Use of the number of cores with cancer and maximum cancer length in biopsy cores failed to improve risk stratification for PSA outcome in all risk groups. CONCLUSIONS: Risk-group stratification based on preoperative variables may significantly improve a physician's ability to counsel patients about PSA outcome after radical prostatectomy. Further improvement in risk stratification may call for use of variables other than the pathologic information in biopsy cores.

Egawa S, Suyama K, Takashima R, Mizoguchi H, Kuwao S, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #10533900 No free full text.

Abstract: BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

Kanoh Y, Egawa S, Baba S, Akahoshi T. · Department of Laboratory Medicine, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan. · J Clin Lab Anal. · Pubmed #19288446 No free full text.

Abstract: We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). All PCa patients with alpha2M deficiency had multiple bone metastases. Proteases in ten PCa patients with and without alpha2M deficiency were studied and compared against ten healthy controls in order to elucidate the relationships between changes in sugar chain structure and neoplasia. We assessed the relationship between ratios of Fr4 to Fr1 and Fr2 (Fr4/Fr1+Fr2 ratios) of oligosaccharide chains, and ratios of free prostate-specific antigen (PSA) to total PSA (F/T ratios), and serum levels of matrix-metalloproteinase-2 (MMP-2) in PCa progression. Measurement of serum alpha2M concentration was performed by laser nephelometry. Serum PSA and MMP-2 levels were determined by enzyme immunoassay and free PSA by radioimmunoassay. N-linked oligosaccharides of human serum immunoglobulin G were analyzed using fluorophore-associated carbohydrate electrophoresis. In those PCa patients with alpha2M deficiency: (a) serum alpha2M and F/T ratios were lower (P<0.05) and (b) Fr4/Fr1+Fr2 ratios and serum MMP-2 levels were higher when compared with those PCa patients without alpha2M deficiency. There was a significant correlation between Fr4/Fr1+Fr2 ratios and F/T ratios or serum MMP-2 levels in PCa with alpha2M deficiency (P<0.05). Therefore, these markers may serve as an auxiliary serum tumor marker for monitoring of the bone metastases or progression of disease in PCa.

Ishiyama H, Satoh T, Kitano M, Kotani S, Uemae M, Baba S, Hayakawa K. · Department of Radiology, Kitasato University School of Medicine, Sagamihara, Japan. · Int J Clin Oncol. · Pubmed #19225925 No free full text.

Abstract: BACKGROUND: The purpose of this study was to assess the impact of hormone therapy on post-implant dosimetry in patients in whom pre-plan and interactive-plan techniques were used for transperineal brachytherapy against prostatic cancer. METHODS: The subjects comprised 244 patients treated using (125)I seed implantation as monotherapy. The prescribed dose to the periphery of the prostate was 145 Gy. The pre-plan technique was used for 116 patients, and the interactive-plan technique for 128 patients. Hormone therapy was used in 71 patients (29.1%). The D90 (dose to 90% of prostate volume) of post-implant computed tomography (CT) analysis was assessed in both groups. In addition, the ratio of post-implant CT volume to preoperative ultrasonography (US) volume was assessed. RESULTS: In the pre-plan group, D90 was significantly lower for patients who received hormone therapy than for those who did not (P = 0.035). However, in the interactive-plan group, D90 did not differ between patients with and without hormone therapy (P = 0.467). The CT-to-US prostate volume ratio was 1.022 for patients who received hormone therapy and 0.960 for patients who did not (P = 0.021). CONCLUSION: Post-traumatic swelling following implantation is increased by cessation of hormone therapy and may reduce D90. However, the present results suggest that the interactive-plan technique overcomes this disadvantage of hormone therapy.

Sakata T, Ferdous G, Tsuruta T, Satoh T, Baba S, Muto T, Ueno A, Kanai Y, Endou H, Okayasu I. · Fuji Biomedix, Department of Pathology, Kitasato University School of Medicine, Chuou, Japan. · Pathol Int. · Pubmed #19121087 No free full text.

Abstract: To find reliable biomarkers for high-grade malignancy, the relationship between immunohistochemical L-type amino-acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki-67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and <0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis.

Satoh T, Ishiyama H, Matsumoto K, Tsumura H, Kitano M, Hayakawa K, Ebara S, Nasu Y, Kumon H, Kanazawa S, Miki K, Egawa S, Aoki M, Toya K, Yorozu A, Nagata H, Saito S, Baba S. · Department of Urology, Kitasato University School of Medicine, Kangawa, Japan. · BJU Int. · Pubmed #19040526 No free full text.

Abstract: OBJECTIVE: To examine the incidence, timing, and magnitude of the prostate-specific antigen (PSA) level 'bounce' after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer. PATIENTS AND METHODS: A multi-institutional pooled analysis was carried out in 388 consecutive patients with T1-T2N0M0 prostate cancer treated with (125)I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had >or=1 year of follow-up and at least three follow-up PSA level measurements. Three definitions of PSA bounce were used: definition A, a PSA level rise of 0.1 ng/mL; definition B, a PSA level rise of 0.4 ng/mL; and definition C, a PSA level rise of 35% over the previous value, followed by a subsequent fall. RESULTS: The actuarial likelihood of having PSA bounce at 24 months was 50.8% for definition A, 23.5% for definition B, and 19.4% for definition C. The median time to develop PSA bounce was 12 months for definition A, 18 months for definition B, and 18 months for definition C. There was a PSA bounce magnitude of 2 ng/mL in 5.3% of patients, and 95.3% of PSA bounce occurred within 24 months after (125)I-BT. Among the before and after (125)I-BT factors, clinical stage, initial PSA level, and Gleason score did not predict for PSA bounce using any definition; only being younger predicted for PSA bounce on multivariate analysis (P < 0.001). CONCLUSIONS: PSA bounce is a common phenomenon after (125)I-BT and occurred at a rate of 19-51% in the Japanese men who underwent (125)I-BT, depending on the definition used. It is more common in younger patients, and early PSA bounce should be considered when assessing a patient with a rising PSA level after (125)I-BT, before implementing salvage interventions. Furthermore, PSA bounce magnitude might be lower in Japanese than in Caucasian patients.

Ishiyama H, Kotani S, Satoh T, Uemae M, Baba S, Hayakawa K. · Department of Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, 228-8555, Japan. · Radiat Med. · Pubmed #18975055 No free full text.

Abstract: PURPOSE: The aim of this study was to assess the variation of probe rotation angles for detecting a single needle using sagittal images of transrectal ultrasonography (TRUS). MATERIALS AND METHODS: A phantom study was performed. One needle was inserted through each of 10 holes of the template, and variations in the probe rotation angles for detecting the needle were measured. RESULTS: The mean variation of probe rotation for detecting a single needle was 17.0 degrees (range 4 degrees -25 degrees ). Slightly broader variation was seen for the needle in holes farther away from the probe. CONCLUSION: Probe rotation angles for detecting a single needle displayed considerable variation. Seed locations recognized on sagittal imaging by TRUS are thus indeterminate, and real-time dose calculations using TRUS for (125)I seed implantation should be used with care.

Ishiyama H, Nakamura R, Satoh T, Tanji S, Uemae M, Baba S, Hayakawa K. · Department of Radiology, Kitasato University School of Medicine, Sagamihara Japan. · Radiother Oncol. · Pubmed #18701179 No free full text.

Abstract: Purpose. The present study investigated inter-software variability in automatically detected seed location and dose volume histogram (DVH). Materials and methods. Image sets from computed tomography (CT) of 25 patients treated using interstitial permanent brachytherapy were examined. Interplant and Variseed were used as software for post-implanted CT analysis. Seed locations are automatically detected by Variseed and Interplant. Dose-volume histograms were calculated using seed locations as detected by the two programs. DVH parameters were compared between Variseed and Interplant. Results. Considerable differences in DVH parameters existed between Variseed and Interplant. For example, mean differences in dose to 90% of prostate volume (pD90) and dose to 5% of urethral volume (uD5) were 8.27 Gy and 20.18 Gy, respectively. The difference in uD5 was associated with prostate volume. Conclusion. Our results suggest that considerable inter-software variability exists in post-implanted CT analysis. DVH parameters from other software should be used with care.

Kanoh Y, Ohara T, Egawa S, Baba S, Akahoshi T. · Department of Laboratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan. · J Clin Lab Anal. · Pubmed #18623104 No free full text.

Abstract: We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). In order to elucidate the relative proportions of free and a prostate-specific antigen (PSA) complex in PCa patients with alpha2M deficiency, we have assessed serum alpha2M and total PSA levels, and ratios of free PSA to total PSA (F/T ratios) at each stage of PCa. Moreover, the PSA reactivity profile was determined on fractionated serum specimens of PCa patients using high-performance liquid chromatography (HPLC) using a TSKG-3000 SWXL column. Measurement of alpha2M concentration was performed by laser-nephelometry. PSA levels were determined by enzyme immunoassay, free PSA by radioimmunoassay. In those PCa patients with alpha2M deficiency, serum alpha2M and F/T ratios were lower, whereas PSA levels were higher when compared with those PCa patients without alpha2M deficiency (P<0.05). PSA elution profiles on HPLC columns revealed two major peaks. The proportion of PSA-antichymotrypsin (PSA-ACT) increased, whereas the proportion of free PSA decreased in PCa patients with alpha2M deficiency as compared with those PCa patients without alpha2M deficiency. F/T ratios were significantly lower in PCa patients with alpha2M deficiency than in those PCa patients without alpha2M deficiency. PSA-ACT and F/T ratio may be useful for monitoring bone metastasis in PCa.

Namiki S, Kwan L, Kagawa-Singer M, Terai A, Satoh T, Baba S, Arai Y, Litwin MS. · Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1738, USA. · Prostate Cancer Prostatic Dis. · Pubmed #18392046 No free full text.

Abstract: We assessed the impact of bother with urinary and bowel dysfunction on social activities among men in Japan and the United States following primary therapy for localized prostate cancer. In paired longitudinal outcomes studies, we measured general and disease-specific health-related quality of life in 400 Japanese and 427 American men who underwent radical prostatectomy or brachytherapy for localized prostate cancer. Outcomes included the social function domain of the Medical Outcomes Study Short Form-36 and the University of California, Los Angeles Prostate Cancer Index, all of which are scored 0-100. Participants completed the questionnaires before and 1, 12 and 24 months after treatment. Among men who reported any urinary bother, Japanese men had slightly better urinary function than American men (84 vs 77, P<0.01). Before brachytherapy, urinary bother was weakly correlated with social function in both the countries; after brachytherapy, urinary bother was strongly correlated with social function in American but not Japanese men. After brachytherapy, bowel dysfunction had a stronger correlation with social function in American than Japanese men (P<0.05). The bother associated with urinary and bowel dysfunction after surgery or brachytherapy for prostate cancer has a greater impact on social function in American men than in Japanese men.

Namiki S, Kwan L, Kagawa-Singer M, Saito S, Terai A, Satoh T, Baba S, Arai Y, Litwin MS. · Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095-1738, USA. · J Urol. · Pubmed #18001788 No free full text.

Abstract: PURPOSE: We performed a cross-cultural comparison of sexual function and bother in men with localized prostate cancer in the United States and Japan. MATERIALS AND METHODS: A total of 447 Japanese and 427 American men with clinically localized prostate cancer were enrolled in separate studies of health related quality of life outcomes. Sexual function and bother were estimated before treatment with validated English and Japanese versions of the UCLA Prostate Cancer Index. RESULTS: Japanese men were more likely than American men to report poor sexual desire (OR 21.2, 95% CI 12.2-37.0), poor erection ability (OR 16.2, 95% CI 9.7-27.1), poor overall ability to function sexually (OR 16.7, 95% CI 9.7-28.9), poor ability to attain orgasm (OR 1.7, 95% CI 1.3-2.3), poor quality of erections (OR 2.5, 95% CI 1.9-3.5), infrequency of sexual erections (OR 2.3, 95% CI 1.7-3.1), infrequency of morning erections (OR 2.7, 95% CI 1.8-4.2) and intercourse in the previous 4 weeks (OR 2.7, 95% CI 1.9-3.8). However, Japanese men were less likely than American men to be bothered by sexual function (OR 0.36, 95% CI 0.24-0.54). A small subset of 10 Japanese-American men reported sexual function that more closely resembled their counterparts in Japan than in the United States. CONCLUSIONS: We posit that cultural disparities in completing the quality of life surveys explain the differences in sexual activity profiles in Japanese and American men with prostate cancer.

Namiki S, Satoh T, Baba S, Ishiyama H, Hayakawa K, Saito S, Arai Y. · Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Urology. · Pubmed #17141839 No free full text.

Abstract: OBJECTIVES: To investigate health-related quality of life (HRQOL) in Japanese men with localized prostate cancer who underwent prostate brachytherapy (BT) or retropubic radical prostatectomy (RRP). METHODS: A total of 70 patients who underwent BT and 67 who underwent RRP were enrolled in our study. The Medical Outcomes Study 36-Item Short Form (SF-36), University of California, Los Angeles, Prostate Cancer Index, and the International Prostate Symptom Score were administered before and 1, 3, 6, and 12 months after treatment. No patients received neoadjuvant or adjuvant therapy. RESULTS: The RRP group reported significantly lower scores in several domains of the SF-36 at 1 month (P <0.05), but these domains returned to baseline within 6 months. The BT patients reported no significant changes in any of the general HRQOL domains throughout the follow-up period. The RRP group reported a lower posttreatment urinary function score, which reflected leakage, than the BT group. However, the BT patients experienced a significantly delayed recovery of the urinary bother score. The data from the International Prostate Symptom Score showed adverse effects from BT on voiding symptoms for the initial 6 months after treatment. No differences were found in bowel symptoms. RRP was associated with worse sexual function than BT, although nerve-sparing surgery minimized the difference. CONCLUSIONS: The results of this study have indicated that BT and RRP have meaningfully different profiles in the recovery of general QOL. The differences in the recovery of disease-specific HRQOL were pronounced during the first 12 months after treatment.

Matsumoto K, Egawa S, Satoh T, Kuruma H, Yanagisawa N, Baba S. · Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. · Int J Urol. · Pubmed #17010007 No free full text.

Abstract: OBJECTIVES: The objective of this study was to use computer simulation to investigate the optimal biopsy scheme for enhancing the detection of cancer in palpably benign prostate glands. METHODS: The predominant distribution of palpably benign prostate cancer is anterior apex to mid-prostate. We used computer simulation to optimize apical samplings and to simulate the biopsy procedure, including angle and length. A total of 254 consecutive patients with palpably benign prostate glands underwent sextant biopsy plus two additional deep apical biopsies. RESULTS: Based on the computer simulation, lateral sextant and two additional medially located deep apical cores with a sagittal penetration angle of 80 degrees had the maximum cancer detection. Of the 254 patients, 58 (22.8%) had prostate cancer: 28 (48.3%) were positive only at the standard sextant sites, 12 (20.7%) were positive exclusively at the deep apical sites, and the remaining 18 (31.0%) were positive at both sites. Patients with gray-zone prostate-specific antigen (PSA) ranges of 4.1-10.0 ng/mL had increased cancer detection rates of 24% compared to sextant biopsy. Enhanced cancer detection by the deep apical biopsy was also evident in patients with a prostatic volume >40 cm3 (by 36.4%) and PSA 2.1-4.0 ng/mL (by 13.3%). CONCLUSIONS: Using a computer simulation-based biopsy scheme with deep apical sampling cores enhanced the detection of prostate cancer in palpably benign glands, especially in men with PSA ranges of 4.1-10.0 ng/mL or a gland volume of >40 cm3. Our approach with fewer sampling cores may have been more cost-effective than other extensive biopsy schemes, but further studies with larger samples are warranted.

Hayashi N, Urashima M, Ikemoto I, Kuruma H, Arai Y, Kuwao S, Baba S, Egawa S. · Department of Urology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. · Prostate Cancer Prostatic Dis. · Pubmed #17003775 No free full text.

Abstract: The aim of this study was to investigate the potential prognostic value of preoperative serum prostate-specific antigen levels adjusted for total tumor volume (PSA-TTV density) for outcome following radical prostatectomy for prostate cancer by retrospective review in 268 patients. Lower PSA-TTV density was not only associated with a significantly higher risk for biological failure (bF), systemic failure and cancer death but also an independent predictor for bF (hazard ratio, 6.3). Therefore, these data suggest that there are subsets of prostate cancer with lower PSA secretion levels, and this phenotype is associated with a higher risk of failure after surgery.

Yokomizo A, Murai M, Baba S, Ogawa O, Tsukamoto T, Niwakawa M, Tobisu K, Kinukawa N, Naito S. · Department of Urology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. · BJU Int. · Pubmed #16925752 No free full text.

Abstract: OBJECTIVE: To evaluate the clinical outcome of radical prostatectomy (RP) in Japan, by retrospectively analysing the clinicopathological data in patients with clinical T1-T2 prostate cancer treated by RP, as there can be prostate-specific antigen (PSA) recurrence after RP in substantially many patients, and its character can differ according to ethnic group and/or country. PATIENTS AND METHODS: We reviewed 1192 patients who had a RP from 1993 to 2002 with no neoadjuvant/adjuvant therapy and whose PSA level after RP decreased at least once to undetectable levels (<0.2 ng/mL). PSA recurrence was defined as > or = 0.20 ng/mL. The patient data were collected from the Urological Oncology Study Group, a subgroup of Japan Clinical Oncology Group. RESULTS: The patients' median (range) age was 67 (47-83) years and their PSA level before RP was 8.7 (1.0-153) ng/mL. During the median follow-up of 45.6 months, 302 of the 1192 patients (25.3%) developed PSA recurrence. The median time to recurrence was 369 (61-2128) days after RP. A log-rank test showed that five significant clinicopathological factors were associated with PSA recurrence after RP: the percentage of prostate needle-biopsy cores with cancer, the biopsy Gleason score, PSA level before RP, pathological stage, and the Gleason score of the RP specimen (P < 0.001 for all). In multivariate analyses, the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were all independent significant predictors of PSA recurrence after RP in Japanese men. CONCLUSIONS: The frequency of PSA recurrence after RP was 25.3% in Japan and the percentage of positive biopsy cores, PSA level before RP, pT and the Gleason score of the RP specimen were independent significant factors for PSA recurrence.