Search

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Objective: Abiraterone acetate has been approved in .70 countries for chemotherapy-naive metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naive Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods: Men, � 20 years, with prostate-specific antigen levels of � 5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy end- point was proportion of patients achieving a prostate-specific antigen decline of � 50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. Results: A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was .35% (threshold re- sponse rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: 266.62%. Median prostate-specific antigen response duration and progression- free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event .Grade 1/2. Conclusions: Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naive metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical trial registration no: NCT01756638.

Objective: In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxelbased chemotherapy. Methods: Men (aged � 20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: � 5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with � 1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a � 50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. Results: Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by � 1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (.20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. Conclusions: Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical trial registration no: NCT01795703.

Purpose: The purpose of this work was to report measured catheter displacement prior to the delivery of highdose-rate brachytherapy (HDR) in the treatment of prostate cancer. Material and methods: Data from 30 prostate cancer patients treated with HDR brachytherapy were analyzed retrospectively. Eighteen transperineal hollow catheters were inserted under transrectal ultrasound guidance. Gold marker seeds were also placed transperineally into the base and apex of the prostate gland. Five treatment fractions of 7.5 Gy each were administered over 3 days. The patient underwent CT scanning prior to each treatment fraction. Catheter displacement was measured from the pre-treatment CT dataset reconstructed at 1.25 mm slice thickness. Results: Most of catheters were displaced in the caudal direction. Variations of 18 catheters for each patient were small (standard deviations < 1 mm for all but one patient). Mean displacements relative to the apex marker were 6 ± 4 mm, 12 ± 6 mm, 12 ± 6 mm, 12 ± 6 mm, and 12 ± 6 mm from plan to 1 st , 2 nd , 3 rd , 4 th , and 5 th fractions, respectively. Conclusions: Our results indicate that catheter positions must be confirmed and if required, adjusted, prior to every treatment fraction for the precise treatment delivery of HDR brachytherapy, and to potentially reduce over-dosage to the bulbo-membranous urethra. J Contemp Brachytherapy 2014; 6, 2: 161–166 DOI: 10.5114/jcb.2014.43619

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent (192)Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥ 6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25-94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.

Fifteen-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) is one of non-enzymatically converted metabolite from prostaglandin D(2) (PGD(2)). Anti-tumor effects of 15d-PGJ(2) in various tumors are partially known, but the detail of in vivo mechanisms of action is still unclear. In this study, we investigated the effects of 15d-PGJ(2) and PGD(2) on murine prostate cancer in vitro and in vivo. Murine prostate cancer cells RM9 were transfected with murine prostaglandin D(2) synthase (mPGDS) gene by using defective retrovirus vector, designated as RM9-mPGDS. In addition, RM9 was also transfected with only defective retrovirus vector, designated as RM9-EV and used as control in this study. The expression and production of the gene were confirmed by RT-PCR and ELISA, respectively. For in vivo study, RM9-mPGDS was injected into the back of C57BL/6 mice, then resulted tumor was used for pathological analysis 14days after the inoculation. Tumor cell apoptosis in the tissue was detected by TUNEL staining. Retrovirally transfected mPGDS in RM9 significantly induced apoptosis in vivo but not in vitro, by TUNEL staining and cell death ELISA, respectively. Our results strongly suggested that the apoptosis induced in RM9-mPGDS in vivo was probably achieved in tumor environment such as hypoxic condition. The introduction of PGDS gene into cancer cells might be a novel therapy against cancer.

Aims: Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a clinically and histologically uncommon benign tumor that can be easily mistaken for a malignant neoplasm. We sought to determine whether immunohistochemical staining would be evaluated IMT of the urinary bladder. We have also shown the literatures that imminohistochemical staining of IMT was investigated to distinguish malignant lesions using PubMed data base. Methods: Immunohistochemical staining, including anaplastic lymphoma kinase (ALK), p53, cytokeratin, vimentin, desmin, alpha-smooth muscle actin, myoglobin, smooth muscle myosin and S100, was carried out on serial sections from archival specimens of three patients who underwent transurethral resection and partial cystectomy. Results: Immunohistchemical staining in all patients was positive for ALK and weak positive for p53 protein. In the literatures, positive rates of ALK and p53 inthe IMT of the urinary bladder were 60.9% and 53.1%, respectively. Sarcoma and carcinosarcoma were shown in the pathological specimens with negative ALK and strongly positive p53 inthe same data base. Conclusions: Both ALK and p53 were potentially useful protein markers to distinguish between IMT and sarcoma. However, this study was small sample size. Further study was warranted an investigation of the availability of these proteins in IMT.

Background Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable. Methods Patients with chemotherapy-naïve mCRPC who were treated with AA after disease progression with enzalutamide, were retrospectively reviewed at five institutions. Primary outcome measure was the rate of any prostate-specific antigen (PSA) decline. Secondary outcome measures were progression-free survival (PFS) and overall survival (OS) with subsequent AA treatment. We also performed correlation analysis between previous PSA response, PFS duration to enzalutamide and subsequent PSA response, PFS duration to AA. Results A total of 14 patients were identified. Any PSA declines and PSA decline ≥50 % with AA treatment, were observed in 36 and 7 % of patients, respectively. Median PFS with initial enzalutamide was 5.0 months (95 % CI 3.7–6.4 months), and for subsequent AA treatment was 3.4 months (95 % CI 0.8–6.0 months). Median OS from initiation of AA was 9.1 months (95 % CI 5.6–12.5 months). No significant correlations were observed between these PSA responses (Pearson r = −0.67, p = 0.82) and PFS duration (Kendall tau r = 0.33, p = 0.87). Conclusions The PSA decline with subsequent AA treatment in chemotherapy-naive mCRPC patients after a failure of enzalutamide was modest, however, the PFS and OS with subsequent AA treatment were comparable to those of enzalutamide previously reported as a second androgen receptor-targeting new agent after AA failure. The PSA response and PFS duration to previous enzalutamide treatment did not predict those of subsequent AA treatment.

Objective(s): We performed a phase IIa clinical trial of trans-1-amino-3-18F-fluoro-cyclobutane carboxylic acid (anti-18F-FACBC), a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326.

cancer and locally advanced prostate cancer patients. The objective of the current study was to examine the rate of adherence to these guidelines within a large-scale population-based data repository. We hypothesized near-perfect guideline adherence. METHODS: Between 2003 and 2009, in the Surveillance Epidemiology and End Results (SEER)-Medicare database, 14,180 patients were diagnosed with high-risk (T1-T2 with WHO histological grade 3), or locally advanced (T3-T4) prostatic adenocarcinoma. We assessed the annual rates of adherence to guidelines with respect to use of RT-ADT in the overall population and after stratification according to stage-grade groupings (T1-T2 G3 vs. T3-T4 any grade), age (66-69 vs. 70-74 vs. 75-79 vs. 80), Charlson comorbidity index-CCI (0 vs. 1 vs. 2) and pre-existing baseline cardiovascular (CV) risk. Linear regression model was used to test the slope of rates of combination treatment over time. Multivariate logistic regression analyses were performed to assess the predictors of RT-ADT use. RESULTS: RT-ADT rates, and guideline adherence, were 58.1 to 75.0%, with the highest rate (75.0%) in 2003, and the lowest (58.1%) in 2009. When stratified according to stage-grade groupings, age, CCI and pre-existing baseline CV risk, similar results were obtained. In multivariate analyses, more recent year of diagnosis (OR 0.90, p

Prostate cancer is now the most commonly diagnosed cancer in Japanese men. In 2015, it is estimated 98,400 new cases are diagnosed. In addition, bone is the most common site for metastasis in prostate cancer, and many patients will develop bone metastases during the natural course of their disease. However, current advances in the diagnosis/treatment of metastatic prostate cancer, lead to change treatment strategy dramatically. In fact, bone metastasis has been changed 'palliative' to 'targeted organ', aimed to extend overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We review the multiple issues involved in current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer, and future directions.

Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue. A 72-year-old female patient with uncontrolled diabetes mellitus was admitted to a hospital with loss of consciousness and, fever. Laboratory data suggested acute inflammation and hyperosmolar hyperglycemic syndrome. The left EPN was accurately diagnosed after abdominal computed tomographic (CT) scan revealed renal parenchymal gas and fluid within the subcutaneous tissue and mediastinum. The patient was transferred to our institution and underwent emergent open surgical drainage. However, a CT scan performed 3 days after the drainage revealed the presence of fluid in the left perinephric space. CT-guided drainage of the left perinephric fluid was performed. The patient was finally discharged after complete recovery from severe inflammation.

Objective: To evaluate risk factors for Denosumab-induced hypocalcemia in prostate cancer patients with bone metastases. Methods: In this single-arm, open-label, prospective multicenter study, 48 prostate cancer patients with bone metastases received Denosumab (120 mg on day 1) and androgen-deprivation therapy. Serum calcium, albumin, alkaline phosphatase (ALP), and phosphate levels; chronic kidney disease stage; and serum prostate specific antigen and urine N-terminal telopeptide (u-NTx) levels were examined. Patients were divided into 2 groups on the basis of whether or not they developed hypocalcemia at 1 week or 1 month after Denosumab administration. Risk factors for hypocalcemia were determined by univariate and multivariate logistic regression analysis. Results: Nineteen patients (39.6%) demonstrated hypocalcemia at 1 week after Denosumab administration, and 16 (33.3%) were hypocalcemic at 1 month. Patients with hypocalcemia at 1 week had higher baseline serum ALP levels (1283.4 ± 1489.7 [mean ± SD] vs 467.3 ± 655.8, P=0.013) than patients without hypocalcemia. Patients with hypocalcemia at 1 month had higher baseline serum ALP (1455.5 ± 1694.1, P=0.002) and u-NTx levels (190.9 ± 63.9, P=0.013) and more bone metastases (extent of disease grade ≥ 3; 10 patients, 20.8%, P=0.006) at baseline than patients without hypocalcemia. Multivariate logistic regression analysis revealed that baseline u-NTx of >100 nmol bone collagen equivalents/mmol creatinine was a significant independent risk factor for hypocalcemia (odds ratio=12.41, 95% confidence interval=1.059-145.600, P=0.049). Conclusions: Baseline u-NTx level is an independent risk factor for Denosumab-induced hypocalcemia in prostate cancer patients with bone metastases.

Purpose The International Commission on Radiological Protection recommends removing the prostate before cremation if death occurs within 12 months after 125 I brachytherapy. However, the incidence of death within this time frame has not been robustly investigated in any country. The purpose this study was to investigate the incidence and cause of death and actions taken when death has occurred within 12 months after 125 I brachytherapy for prostate cancer in Japan. Methods and Materials Data were extracted from the Japan Radioisotope Association database to investigate the total number of implantation cases, number of early deaths after implantation, cause of death, and postmortem actions between September 2003 and the end of June 2010 in Japan. Early death was defined as occurring within 12 months after 125 I brachytherapy for prostate cancer. Results During the study period, 15,427 patients underwent 125 I brachytherapy and 43 (0.28%) died within 12 months after implantation. For 37 of the 43 patients (86%), the brachytherapy source was retrieved together with the prostate gland at autopsy; however, autopsy could not be performed in six (14%) of the deceased patients. The largest proportion of early deaths was because of cerebrovascular or cardiovascular disease (17/43, 40%), followed by malignant tumor (15/43, 35%), and respiratory disease or infection (7/43, 16%). Conclusions The incidence of early deaths within 12 months after 125 I brachytherapy in Japan was 0.28%. In almost all cases, the brachytherapy sources were removed in the intact prostate before the body was cremated and stored appropriately.

Approximately 80% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0 MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3 months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1 month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2 months onward. At 2 months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.

Introduction Erectile dysfunction (ED) is related to several co‐morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. Aim To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). Methods We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log‐rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). Main Outcome Measures The Expanded Prostate Cancer Index Composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC‐SF ≥ 60 points while ED was defined as preoperative EPIC‐SF lower than 60 points. Results Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan‐Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF ( P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). Conclusions These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP. Kimura M, Banez LL, Gerber L, Qi J, Tsivian M, Freedland SJ, Satoh T, Polascik TJ, Baba S, and Moul JW. Association between preoperative erectile dysfunction and prostate cancer features—An analysis from the Duke Prostate Center Database. J Sex Med 12;9:1174–1181.

Recent advances in high-intensity focused ultrasound, which was developed in the 1940s as a viable thermal tissue ablation approach, have increased its popularity. High-intensity focused ultrasound is currently utilized the most in Europe and Japan, but has not yet been approved by the Food and Drug Administration, USA, for this indication. The purpose of the present report is to review the scientific foundation of high-intensity focused ultrasound technology and the clinical outcomes achieved with commercially available devices. Recently published articles were reviewed to evaluate the current status of high-intensity focused ultrasound as a primary or salvage treatment option for localized prostate cancer. Improvements in the clinical outcome as a result of technical, imaging and technological advancements are described herein. A wide range of treatment options for organ-confined prostate cancer is available. However, high-intensity focused ultrasound is an attractive choice for men willing to choose less invasive options, although establishing the efficacy of high-intensity focused ultrasound requires longer follow-up periods. Technological advances, together with cultural and economic factors, have caused a dramatic shift from traditional open, radical prostatectomy to minimally invasive techniques. High-intensity focused ultrasound is likely to play a significant role in the future of oncology practice.

Purpose To compare the efficacy of three α 1A /α 1D -adrenoceptor (AR) antagonists—naftopidil, tamsulosin, and silodosin—that have differing affinities for the α 1 -AR subtypes in treating urinary morbidities in Japanese men with 125 I prostate implantation (PI) for prostate cancer. Methods and Materials This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacy variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). Results Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. Conclusions Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.

Objective: To evaluate the efficacy and toxicity of a gemcitabine and paclitaxel regimen for patients with advanced urothelial carcinoma who had previously been treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and to determine the prognostic factors for survival in second-line chemotherapy. Methods: From June 2005 to April 2010, 24 eligible patients who had previously been treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy were enrolled in this study. Patients received paclitaxel 200 mg/m 2 on Day 1 and gemcitabine 1000 mg/m 2 on Days 1, 8 and 15. The gemcitabine and paclitaxel regimen was repeated every 3 weeks. Patients were evaluated every two cycles by imaging study. Results: Ten of 24 patients (42%) had major response to the gemcitabine and paclitaxel regimen, including 2 patients (8%) who had complete response. Median survival time and median progression-free survival were 12.4 and 6.1 months, respectively. Good performance status and major response to first-line methotrexate, vinblastine, doxorubicin and cisplatin treatment were significant predictors of overall survival and progression-free survival. Grade 3 or 4 neutropenia occurred in 16 patients (67%), but there were no severe infections. There were no treatment-related deaths. Conclusions: Gemcitabine and paclitaxel chemotherapy had favorable benefit and safety profiles, and the regimen is recommended as a potential second-line chemotherapy for advanced or metastatic urothelial carcinoma previously treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy.

Introduction The mechanisms of radiation‐induced erectile dysfunction (ED) are unclear, as clinical studies are limited, and previous animal models were based on wide‐field irradiation, which does not model current radiotherapy (RT) techniques. Aims To perform functional and morphological analyses of erectile function (EF) utilizing image‐guided stereotactic prostate‐confined RT in a rat model. Methods Sixty young adult male rats aged 10–12 weeks old were divided into age‐matched sham and RT groups. A single 20‐Gy fraction to the prostate was delivered to RT animals. Penile bulb, shaft, and testes were excluded from treatment fields. Main Outcome Measures Bioassay and intracavernous pressure (ICP) measurements were conducted at 2, 4, and 9 weeks following RT. Perfusion analysis of the corpora cavernosa (CC) was conducted using Hoechst injected prior to sacrifice. Penile shaft and cavernous nerve (CN) were evaluated by immunohistochemistry. Plasma testosterone level was analyzed using a testosterone enzyme‐linked immunosorbent assay (ELISA) assay kit. Results Irradiated animals demonstrated statistically significant time‐dependent functional impairment of EF by bioassay and ICP measurement from 4 weeks. Neuronal nitric oxide synthase (NOS) expression was decreased in CN by 4 weeks. In CC, expression levels of anti‐alpha smooth muscle actin and endothelial NOS were significantly decreased at 9 weeks. In penile dorsal vessels, smooth muscle/collagen ratio was significantly decreased at 4 and 9 weeks. Additionally, Hoechst perfusion showed time‐dependent decrease in CC of RT animals, whereas CD31 expression was not affected. No toxicities were noted; testosterone levels were similar in both groups. Conclusion We demonstrated time‐dependent ED following image‐guided stereotactic RT. Our results imply that reduction of neuronal NOS expression in cavernous nerve could trigger consecutive reduction of smooth muscle content as well as blood perfusion in CC that resulted in corporal veno‐occlusive dysfunction. Present study could be a cornerstone to future research that may bring comprehensive scientific understanding of radiation‐induced ED. Kimura M, Yan H, Rabbani Z, Satoh T, Baba S, Yin F‐F, Polascik TJ, Donatucci CF, Vujaskovic Z, and Koontz BF. Radiation‐induced erectile dysfunction using prostate‐confined modern radiotherapy in a rat model. J Sex Med 2011;8:2215–2226.

Chemotherapy/Radiation therapy/Chemoradiotherapy/Bladder cancer/Urothelial carcinoma. The objectives of this study were to determine the tolerability of combined use of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with exter nal beam radiation therapy (EBRT) and to access the efficacy in patients with locally advanced or metastatic bladder cancer. From December 2000 to November 2010, 30 eligible patients were enrolled in this study. After receiving one cycle of MVAC treatment, all patients received EBRT with a half dose of MVAC treatment followed by two more cycles of chemotherapy. A standard fractionation with daily dose of 1.8–2.0 Gy was used, with the total dose up to 60 Gy over 5–6 weeks. The four-field box technique was utilized for radiation fields. Thirteen patients (43%) had complete response and 11 (37%) had partial response, with an overall response rate of 80%. The median overall survival and progression-free survival was 25.5 months and 12.8 months, respectively. In the complete-response patients, median overall survival was 37.1 months. Grade 3 or 4 neutropenia occurred in 25 patients (83%), but there were no severe infections. One patient (3%) had hemorrhagic radiation cystitis. There were no treatment-related deaths. Combined use of MVAC treatment with EBRT is a favorable therapeutic option for patients with advanced or metastatic bladder carcinoma. Given the safety and benefit profile found in this study, appropriate case selection is warranted in the future.

Purpose To compare the results of intraoperative ultrasound (US)-based dosimetry with those of postimplant computed tomography (CT)-based dosimetry after 125I prostate brachytherapy. Methods and Materials Subjects comprised 160 patients who underwent prostate brachytherapy using 125I seed implants. Prescribed dose was set as 145 Gy to the periphery of the prostate. Implantation was performed using an intraoperative interactive technique. Postimplant dosimetry was performed on Days 1 and 30 after implantation using CT. Dosimetric results for the prostate, urethra, and rectum were compared among intraoperative US and CT on Day 1 (CT1) and Day 30 (CT30). Results Mean minimal dose received by 90% of prostate volume was 133.7%, 115.6%, and 125.8% of the prescribed dose on US, CT1, and CT30, respectively: This value temporarily decreased on Day 1 and increased on Day 30. Other parameters for the prostate and urethra showed similar trends. Conversely, mean rectal volume receiving 100% of the prescribed dose was 0.69, 0.46, and 1.02 mL on US, CT1, and CT30, respectively. Rectal parameters tended to be underestimated on US relative to CT30-based dosimetry. A positive linear relationship was identified between US and CT observations for every prostate parameter and the dose covering 30% of the urethra. Conclusions Our results demonstrate significant differences between dosimetric parameters obtained by US, CT1, and CT30. However, significant correlations also exist between US and CT, at least in prostate and urethral parameters. Clarification of the degrees of difference might make US planning more feasible.

In addition to open surgery, curative therapies for prostate cancer now include endoscopic surgery and radiation therapies. Because of the expansion and subdivision of treatment methods for prostate cancer, the medical fee point schedule in Japan was revised in fiscal year 2006. We examined changes in medical income and expenditure after this revision of the medical fee system.We studied income and expenditure, after institution of the new medical fee schedule, for the five types of therapies for prostate cancer performed at our hospital: two surgical therapies (radical retropubic prostatectomy and laparoscopic prostatectomy) and three radiation therapies (three-dimensional conformal radiation therapy, (192)Ir high-dose-rate brachytherapy, and (125)I low-dose-rate brachytherapy).Low-dose-rate brachytherapy was found to be associated with a profit of yen199 per patient. Laparoscopic prostatectomy, a highly advanced medical treatment that the fee revision changed from a partially insured to an insured procedure, yielded a profit of yen75,672 per patient. However, high-dose-rate brachytherapy was associated with a loss of yen654,016 per patient.Given the loss in hospital income per patient undergoing high-dose-rate brachytherapy, the medical fee point system for this procedure should be reassessed.

Purpose To evaluate the severity of genitourinary (GU) toxicity in high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiotherapy (EBRT) for prostate cancer and to explore factors that might affect the severity of GU toxicity. Methods and Materials A total of 100 Japanese men with prostate cancer underwent 192 Ir HDR brachytherapy combined with hypofractionated EBRT. Mean (SD) dose to 90% of the planning target volume was 6.3 (0.7) Gy per fraction of HDR. After 5 fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administrated. The urethral volume receiving 1–15 Gy per fraction in HDR brachytherapy (V1–V15) and the dose to at least 5–100% of urethral volume in HDR brachytherapy (D5–D100) were compared between patients with Grade 3 toxicity and those with Grade 0–2 toxicity. Prostate volume, patient age, and International Prostate Symptom Score were also compared between the two groups. Results Of the 100 patients, 6 displayed Grade 3 acute GU toxicity, and 12 displayed Grade 3 late GU toxicity. Regarding acute GU toxicity, values of V1, V2, V3, and V4 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0–2 toxicity. Regarding late GU toxicity, values of D70, D80, V12, and V13 were significantly higher in patients with Grade 3 toxicity than in those with Grade 0–2 toxicity. Conclusions The severity of GU toxicity in HDR brachytherapy combined with hypofractionated EBRT for prostate cancer was relatively high. The volume of prostatic urethra was associated with grade of acute GU toxicity, and urethral dose was associated with grade of late GU toxicity.

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 125I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had ≥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 125I-BT. Among the before and after 125I-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

OBJECTIVES The lymphatic vessel endothelial hyaluronan receptor (LYVE-1) is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells. The objective of this study was to determine the LYVE-1 expression patterns in normal urothelium and to compose the geometric topography of the lymphatic network. METHODS Immunohistochemical staining for LYVE-1 and von Willebrand factor was performed to assess the differences in the distribution of lymphatic vessels between the components in the urinary bladder. The sizes of the individual lymphatic vessels were categorized as small, medium, and large. To compare the lymphatic density (counts per square millimeter), the number of lymphatic vessels of the five random areas was counted in each specimen. RESULTS LYVE-1 expression and the lymphatic density of the muscularis propria were significantly greater than those of other layers, including the epithelium, lamina propria, perivesical fat, and serosa (P

OBJECTIVES Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival. METHODS Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes. RESULTS UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P

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

We performed a cross-cultural comparison of sexual function and bother in men with localized prostate cancer in the United States and Japan.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.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.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.

Objectives: We report that a combination of gemcitabine and paclitaxel will effectively treat patients with advanced urothelial carcinoma (UC) who have been previously treated with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). The objective of this study was to assess the tumor responses, toxicity, and overall survival of these patients as second-line treatment. Methods: Ten eligible patients were enrolled in this study. All patients had been previously treated with MVAC. Patients received paclitaxel 200 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1, 8, and 15. The treatment was repeated every 21 days. Tumors were assessed every two cycles by imaging study. Results: The median number of treatment courses was 4 (range 2–7). Two patients had complete response and five patients had partial response after two courses of treatment. Median overall survival was 10.3 months. Median overall survival from the first MVAC was 19.1 months. Median progression-free survival was 4.1 months. Of the seven responders, median progression-free survival was 7.4 months. Myelosuppresion was the most common toxicity. Nonhematologic toxicity consisted of hypersensitivity reactions to paclitaxel. There were no therapy-related deaths. Conclusions: Gemcitabine and paclitaxel chemotherapy is a favorable therapeutic alternative for patients with advanced or metastatic UC who have previously been treated with MVAC chemotherapy. Given the safety and benefit profile seen in this study, a large prospective research study is warranted to consider the potential role of gemcitabine and paclitaxel chemotherapy as a second-line treatment for urothelial cancer.

AIM: To investigate the time course of testosterone (T) recovery after cessation of androgen deprivation therapy (ADT) in patients treated with brachytherapy. METHODS: One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group (≤ 12 mo, n = 91) and a long-term usage group (≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term group. RESULTS: Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessation were 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group (P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels (< 10 ng/dL) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the long-term usage group (P = 0.002). CONCLUSION: Lower T levels at cessation of ADT were associated with prolonged T recovery in the long-term usage group. Five years after cessation of long-term ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.

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

BACKGROUND: Oncocytic L-amino acid transporter (LAT) 1 could be a target of new molecular therapy against malignancies. OBJECTIVE:To assess the correlation between overexpression of LAT1 and local progression (LP) in prostatic carcinoma (PC) patients under expectant management (EM). METHODS: This retrospective study analyzed 109 patients with PC who received EM from 1991 to 2006. The expression of LAT1, LAT2, and CD98, as well as Ki-67 labeling indices (LI), was analyzed immunohistochemically in first biopsy or TUR samples diagnosed as adenocarcinomas. RESULTS: Of the 109 patients, 44 (40%) showed LP on clinical examinations, whereas 65 showed stable disease (SD). LAT1 score and intensity were significantly higher in the LP than in the SD group, as well as among Gleason score (GS)-low (GS < 7) patients who were associated with low-risk. When the LP group was subdivided by D’Amico risk category (low-, intermediateand high-risk groups), each showed higher LAT1 expression than the SD group. LAT1 expression did not correlate with GS or Ki-67 LI. CONCLUSIONS: Independently of GS, aberrant overexpression of LAT1 in prostatic adenocarcinoma could predict LP under EM. Although prostate biopsy samples are small, LAT1 may be a novel prognostic biomarker of LP.

Objective: Abiraterone acetate and docetaxel are promising treatment options for metastatic castration-resistant prostate cancer patients. However, the optimal sequencing of these agents is unclear, and no previous reports discuss Japanese metastatic castration-resistant prostate cancer patients. The purpose of this analysis is to reveal the outcomes of Japanese metastatic castrationresistant prostate cancer patients treated with abiraterone acetate followed by docetaxel. Methods: We retrospectively reviewed Japanese Phase 1 and Phase 2 trials of metastatic castrationresistant prostate cancer patients treated with abiraterone acetate until disease progression and subsequently treated with docetaxel. The primary outcome measure was the rates of prostate-specific antigen declines ≧30 and ≧50%, respectively, with docetaxel. Secondary outcome measures included progression-free survival with docetaxel, and overall survival after initiation of abiraterone acetate and docetaxel. We performed correlation analysis between previous prostate-specific antigenresponse toabiraterone acetate and subsequentprostate-specific antigenresponse todocetaxel. Results: We identified 15 patients had experienced disease progression with abiraterone acetate and subsequently were treated with docetaxel. Prostate-specific antigen declines ≧30 and ≧50% with docetaxel were observed in five patients (33%) and two patients (13%), respectively. The median progression-freesurvivalwith docetaxel was 3.7 months(95% confidence interval: 2.9–4.6). The median overall survivalfrominitiationofdocetaxelandabirateroneacetatewere14.4months(95%confidenceinterval: 6.3–22.4), and 25.7 months (95% confidence interval: 20.1–30.7), respectively. No significant correlation was observed between these prostate-specific antigen responses (Pearson r= 0.206, P=0.46). Conclusion: The efficacy of docetaxel in Japanese mCRPC patients that was resistant to abiraterone acetate was modest. The prostate-specific antigen response to previous abiraterone acetate could not predict the efficacy of subsequent docetaxel. Larger prospective trials are needed to validate these findings.

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° 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.

The limitations of current forms of prostate cancer therapy have driven researchers to search for new alternatives. Previously we showed cytopathic effect related to HSV-tk in prostate cancer. In this study we present initial results of a neoadjuvant HSV-tk gene therapy trial and address some of the potential mechanistic aspects of its effect in human tissues. We enrolled 23 men with clinically localized prostate cancer but high risk for recurrence in this Phase I-II trial. Intraprostatic viral injections (one to four) were followed by 2 weeks of ganciclovir and prostatectomy 2-4 weeks later. Toxicity was modest. Surgical specimens were embedded fully and whole-mount slides were imaged and analyzed for areas of cytopathic effect. The larger the tumor the greater the cytopathic effect. The effect also seems to be related to areas of high CAR expression. However, the number of injection sites did not influence effect. Local (CD8+ cells and macrophages) and systemic immune response (CD8+ and activated CD8+, IL-12) was increased in patients treated with HSV-tk. Increased apoptosis and decreased microvessel density were also noted in these patients. The results suggest a tumor-specific effect mediated by systemic and local immune response, antiangiogenic effect, and modulation of apoptosis.

Background: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. Methods: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, 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 pretreatment prostate-specific antigen (PSA) level were 70 years (range 44–88) and 9.76 ng/mL (range 3.39–89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4–68). Results: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01–20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P

We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene-modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing beta-galactosidase (Adbetagal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Adbetagal-cell vaccine (P

Two patients with prostate cancer showed cranial nerve palsies due to skull base metastases. Case 1: A 64-year-old man had prostate cancer (T4 N0 M1, Gleason score 7, prostate-specific antigen [PSA] level 372 ng/mL) with multiple bone metastases. Seventy-seven months after initiation of therapy, he had an articulation disorder and palsy of the left side of the tongue, with 12th cranial nerve palsy. Case 2: A 75-year-old man had a prostate cancer (T3b N0 M1, Gleason score 7, PSA level 177 ng/mL) with multiple bone metastases. Sixty-six months after initiation of therapy, he had hearing loss, noise in the right ear, and dizziness, with 8th cranial nerve deficits. Magnetic resonance imaging showed low intensity in the clivus in both cases, and all over the skull in case 2. The first patient was treated with radiation therapy and intravenous steroids at an early date. His symptoms improved.

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.

To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin.In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively.The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of10, 10.01-20 and20 ng/mL were 82%, 62% and 20% (P0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of0.2, 0.21-1 and1 ng/mL were 100%, 74% and 21% (P0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P0.001) was a significant independent predictor of relapse.HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.

To perform systemic 22-core transperineal ultrasound-guided template prostate biopsies in patients with previous negative transrectal ultrasound-guided prostate biopsy findings and evaluate the cancer core distribution.Between April 2001 and December 2003, 128 men underwent systemic ultrasound-guided biopsy using the transperineal template technique. All patients had undergone at least one previous set of biopsies. Prostate biopsy was performed transperineally using an 18-gauge biopsy needle driven by a spring-loaded device. Four biopsies were obtained anterior to posterior from each of four coronal planes in the mid-region, and three biopsies were obtained anterior to posterior from each of two coronal planes in the apical region.Of the 128 patients, 29 (22.7%) had cancer according to an extended transperineal biopsy. Patients with prostate cancer had significantly greater prostate-specific antigen (PSA) levels (11.4 versus 7.6 ng/mL, P = 0.0125), smaller transition zone volumes (12.7 versus 21.2 cm3, P = 0.0012), smaller prostate glands (31.5 versus 44.0 cm3, P = 0.0015), and greater PSA density (0.36 versus 0.19 ng/mL/cm3, P0.0001). The cancer core rates in the mid and apical parts of the anterior region (5.3% and 8.0%) were significantly greater than in the mid and apical parts of the posterior region (3.3% and 3.6%, P = 0.0297 and P = 0.0132, respectively).The results of our study have shown that transperineal approaches are appropriate for sampling from the anterior half of the prostate gland. In patients in whom the diagnosis of prostate cancer is suspected, we believe that systemic 22-core transperineal ultrasound-guided template prostate biopsy might be the next optional diagnostic step after an initial negative prostate biopsy.

Cancer prevention in people occupationally exposed to carcinogens that cause bladder cancer has focused on early cancer detection by use of traditional screening methods including hematuria testing, urinary cytology, and cystoscopy. However, these screening methods showed limitations in terms of reducing mortality from bladder cancer. Currently, several molecular substances have shown potential as screening markers for bladder cancer. This article reviews epidemiologic cohort studies, hematuria screening, and the biologic molecular markers for bladder cancer related to occupational carcinogenicity. Considering the long latency period, new cases of occupational bladder cancer have been expected to occur more frequently. Because of recent advances in molecular techniques, biologic markers have a potential role in screening for and monitoring of occupational bladder cancers.

We report a case of dissemination of prostate cancer after holmium laser enucleation of the prostate in an 80-year-old patient. The patient presented at hospital because of nocturia. Transrectal ultrasound-guided biopsy was carried out because of high serum prostate-specific antigen (3.55 ng/mL), but it showed no malignancies. Benign prostate hyperplasia was diagnosed, and he was started on an α1-blocker. Although the urinary symptom improved with silodosin, acute urinary retention occurred 3 years after therapy began. Holmium laser enucleation of the prostate for relief of bladder outlet obstruction enabled discharge of urine. Pathological examination of the resected tissue found adenocarcinoma with a high Gleason score, 4 + 5. Serum alkaline phosphatase increased rapidly after holmium laser enucleation, and bone scintigraphy confirmed multiple bone metastases. Prostate cancer, T1bN0M1b, was diagnosed.

In situ cytotoxic gene therapy can potentially trigger a systemic immune response, which could impact occult metastatic disease. We are currently conducting three clinical trials using in situ adenoviral vector mediated herpes simplex virus-thymidine kinase (HSV-tk) gene delivery followed by the HSV-tk prodrug ganciclovir (GCV) or valacyclovir (VCV). This study evaluates the systemic T-cell response after gene therapy in each trial.The study protocol included three separate clinical trials in the Baylor Prostate Cancer SPORE Program: Trial A gene therapy in prostate cancer patients failing radiotherapy (36 patients), Trial B neoadjuvant gene therapy in pre-radical prostatectomy patients (22 patients), and Trial C gene therapy in combination with radiotherapy for prostate cancer (27 patients). Heparinized blood was collected at the time of vector injection and at selected intervals afterward. A complete blood count was performed, and peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting after labeling with dual color-labeled antibody pairs.The pretreatment mean percentage of activated CD8+ T cells (DR+CD8+ T cells) was 12.23%, 16.72%, and 14.09% (Trials A, B, and C, respectively). Two weeks posttreatment, this increased to 22.87%, 26.15%, and 39.04% (Trials A, B, and C, respectively), and these increases were statistically significant (p = 0.0188, p = 0.0010, p0.0001, respectively). The increase of DR+CD8+ T cells was significantly larger in Trial C than in Trial A (p = 0.0044) or Trial B (p = 0.0288). Total CD8+ T cells significantly increased at 2 weeks posttreatment in Trial B and C (p = 0.0013, p = 0.0004, respectively). Interestingly, only in Trial C were significant increases in activated CD4+ T cells seen at 2 weeks (p = 0.0035).This is the first report of systemic T-cell responses after HSV-tk+GCV/VCV gene therapy under three clinical trial conditions. There was an increase in activated CD8+ T cells in the peripheral blood after vector injection, suggesting the potential for activation of components of cell-mediated immune response in all trial conditions. The addition of radiotherapy to in situ gene therapy seems to further increase the total CD8+ T cells and activated CD4+ T cells.