Organ-confined Prostate Cancer Patients Research Articles

Retrospective Analysis of Clinical Outcomes of Stereotactic Body Radiation Therapy for Localized Prostate Cancer at an Asian Cancer Specialist Centre.

The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer. All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale. Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D'amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively. SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

Long Term Outcomes in Patients with High and Intermediate-Risk Prostate Cancer Treated with High Dose Rate Brachytherapy Boost or Igrt Boost. A Role for Brachytherapy

Brachytherapy (BT), High Dose Rate (HDR) are employed as a boost for intermediate (IR) (PSA 10-20 ng/ml, Gleason ≤ 7 and ≤ T2c) and high risk (HR) (PSA >20 ng/ml, Gleason 8-10 and ≥T3) prostate cancer. A retrospective analysis in 261 consecutives organ confined prostate cancer patients treated from October 2004 to December 2015 has been made for evaluating the clinical results and toxicity comparing EBRT exclusive with combined treatments of EBRT and a HDR BT component.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p=0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04ng/ml/month, p=0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p<0.0001), PSA nadir≥2ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p=0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Clinical validation of real-time tissue change monitoring during prostate tissue ablation with high intensity focused ultrasound

BackgroundThe purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature.MethodsPost in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients’ data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter.ResultsIn the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C.ConclusionsThe TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Abstract 3803: Characterization of fluid biopsy using the HD-SCA platform to re-stratify intermediate-risk organ-confined prostate cancer patients

Abstract Recent studies have demonstrated that even with current risk stratification of intermediate-risk organ-confined prostate cancer patients, 30-50% of patients are incorrectly categorized and overtreated. As the second leading cause of cancer in men, 90% of prostate cancer patients are diagnosed at organ-confined stages, where radical prostatectomy (RP) is the “golden standard” of treatment. However, deferring intervention is becoming a more popular option for low-risk patients, with a 15-year progression-free survival of 95%. High-risk patients greatly benefit from RP, with a 5-year progression-free survival of 85%, while the decision to proceed with RP is not so candid for intermediate-risk patients. Using the high-definition single cell assay (HD-SCA) platform, circulating tumor cells (CTCs) from peripheral blood (PB) and disseminating tumor cells (DTCs) from bone marrow aspirate (BMA) will be analyzed for morphological, genomic, and proteomic profiling. We hypothesize that by using morpho-proteo-genomic parameters we may develop predictive markers for a more accurate stratification of intermediate-risk patients, offering a more personalized treatment for each individual. Preliminary data shows 86% (n=43) of PB samples and 5% (n=40) of BMA are positive for Cytokeratin (CK) expressing rare circulating cells, as defined by ≥5 cells/mL. The incidence of CK+ cells in PB did not correlate with PSA, Gleason score, or clinical parameters. However, incidence of CK+ cells in PB was higher in high-risk group, though not statistically significant (p=0.784) when compared to intermediate-risk groups. Additionally, higher levels of CK expression (p&amp;lt;0.0001), as measured by relative intensity of fluorescent staining, were detected in cells detected in PB of high-risk patients relative to intermediate- and low-risk groups as measured by an analysis of variance (ANOVA) statistical model. Low levels of genomic aberrations are observed in all CK+ rare circulating cells (5%, n=118), which may speak to the fact that these patients are in early stages of their disease. The use of the HD-SCA platform to characterize the fluid biopsy may result in the identification of predictive markers of treatment response for intermediate-risk patients, resulting in reduction of overtreatment. Citation Format: Paymaneh D. Malihi, Kenneth Pienta, James Hicks, Michael Gorin, Carmen Ruiz Velasco, Anders Carlsson, Anand Kolatkar, Mariam Rodriguez Lee, Michael Morikado, Peter Kuhn. Characterization of fluid biopsy using the HD-SCA platform to re-stratify intermediate-risk organ-confined prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3803. doi:10.1158/1538-7445.AM2017-3803

Dosimetric comparison between treatment plans of patients treated with low-dose-rate vs. high-dose-rate interstitial prostate brachytherapy as monotherapy: Initial findings of a randomized clinical trial

PurposeThe aim of this study was to compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose–rate (LDR) and high-dose–rate (HDR) interstitial brachytherapy (BT). Methods and MaterialsA randomized clinical trial was initiated at our institution to compare the results and side effects of LDR and HDR BT as monotherapy in the treatment of early, organ-confined prostate cancer patients. Eighty-seven patients were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR 125I seed BT with 145 Gy. Inverse optimization algorithms were used for planning. Stranded seeds were implanted using live ultrasound imaging after preimplant treatment planning. Final dosimetry of HDR treatments was based on updated needle and contour positions. Statistical comparisons with nonparametric test were performed between the corresponding dose–volume parameters. ResultsThe V100 and V150 were 99% and 61%, respectively, for LDR, whereas 98% and 32% for HDR treatments. The D90 was less for HDR (122% vs. 110%). The dose distributions were more homogeneous and conformal with HDR technique (dose homogeneity index, 0.39 vs. 0.67; conformal index, 0.65 vs. 0.80). The urethra and rectum received significantly less dose with HDR. The D10 and D30 for urethra were 133% and 128%, respectively, for LDR and 114% and 111% for HDR treatments. The D2cm3 for rectum was 68% and 55% for LDR and HDR technique, respectively. ConclusionsBoth techniques provided acceptable target volume coverage with a slightly higher value with the LDR technique. The dose distributions were more homogeneous and conformal, and both urethra and rectum were better protected with the HDR technique.

The Value and Evaluability of the PCA3 Urine Assay in Prostate Carcinoma is Independent of the Tumor Localization.

The prostate cancer gene 3 (PCA3) test is based on the analysis of tumor cell mRNA in urine. As an exprimated urinary marker, its retrieval is subject to certain physical aspects like palpation pressure and detachment force during the squeezing of cells. Other potential factor of influence may be the distance the cells have to cover until they reach the urethra. Thus, it was investigated whether the localization of the tumors within the prostate with regard to the urethra and the seminal colliculus influences the PCA3 score. Prostatectomy specimens of 55 organ-confined prostate cancer patients were processed according to the Stanford protocol. For each prostatectomy specimen, a three-dimensional reconstruction including the surface of the prostate, the tumor areas and the urethra was created. By model simulating, virtual concentric tubes were placed around the urethra and spherical volumes were virtually positioned around the seminal colliculus at diameters of 8, 16 and 32mm. Depending on localization, tumor volumes may or may not protrude into the tubes or spherical volumes. For each respective diameter, PCA3 levels were compared between the subgroup with and without protrusion of tumor tissue into the tube or spherical ball. For none of the diameters, whether in tubes or spherical balls, were patients without intersection volumes-hence showing peripherally located tumors-found to have lower PCA3 levels. No clinical or histopathological parameter correlated with the PCA3 score. The location of the tumor mass in the prostate with respect to the urethra or the seminal colliculus did not to affect the PCA3 score. Hence, the location of the tumor does not limit the validity of the PCA3 score, and even for exclusively peripherall y located tumors, this possible influencing factor did not lead to an artificial modulation of the PCA3 score.

Dosimetric Comparison between Treatment Plans of Patients Treated with Low-Dose-Rate Versus High-Dose-Rate Interstitial Prostate Brachytherapy as Monotherapy: Initial Findings of a Randomized Clinical Trial

To assess and compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose rate and high-dose rate interstitial brachytherapy. A randomized clinical trial was initiated at our institution to compare the results and side effects of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) as monotherapy in the treatment of early, organ confined prostate cancer patients. Fifty patients with low and selected intermediate risk prostate cancer were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR I-125 seed BT with 145 Gy. In both techniques the implantation was performed with transrectal ultrasound guidance in spinal anesthesia, and intraoperative dose plans were made on ultrasound images using inverse optimization algorithms (IPSA for LDR and HIPO for HDR). Dose-volume constraints for prostate, urethra and rectum were applied during optimization. Stranded seeds were implanted into the prostate using live ultrasound imaging following preimplant treatment planning. The HDR treatments were performed after preimplant planning, but final dosimetry was based on updated needle and contour positions. Treatment plans were compared using dose-volume histograms, dose coverage metrics including V100, V150, conformal index (COIN) and dose homogeneity index (DHI) for prostate. Dose to urethra was characterized by D10, D30, D0.1cc and D0.01cc. Dose to rectum was described by D2cc, D1cc, D0.1cc, D0.01cc and D10. Statistical comparisons with non-parametric test were performed between the corresponding parameters. The median needle number was 20 and 18 for LDR and HDR treatments, respectively. The mean seed number was 46.The total seed activity was 26.8 mCi with individual median seed activity of 0.562 mCi. The target coverage by the prescribed dose was larger than 95% for both patient groups, and the V100 was higher for LDR patients. The other parameters are shown in the table.To make the comparison more easy dose parameters are given in relative values, in percentages related to prescribed dose. Except for volume of the prostate the difference between the means of all other parameters for the two patient groups was statistically significant (p<0.05). Both techniques provided acceptable target volume coverage, but higher percentage of target volume was irradiated by the prescribed dose with LDR technique. The dose distributions were more homogeneous with HDR technique, and both urethra and rectum received less relative dose in patients treated with HDR technique. To assess whether these dosimetric data translate in differences in clinical outcomes more patient data and longer follow-up are needed.Tabled 1ProstateV (ccm)V100V150DHICOINLDR32.299620.370.64HDR35.497300.700.80UrethraV (cc)D10D30D0.1ccD0.01ccLDR1.4135129136.0146.9HDR1.6113110113.1115.3RectumD2ccD1ccD0.1ccD0.01ccD10LDR67.179.098.4111.288HDR54.762.875.781.067 Open table in a new tab

Analysis of different tumor volume thresholds of insignificant prostate cancer and their implications for active surveillance patient selection and monitoring.

Purpose:We compared oncological outcomes according to tumor volume (TV) thresholds defining both classical and updated insignificant prostate cancer (IPC), since the TV threshold can be used as clinical parameter for active surveillance.Methods:Between 2001 and 2012, we retrospectively analyzed 331 organ-confined prostate cancer patients who had preoperative Gleason score 6, preoperative PSA under 10 ng/mL and pathologic TV less than 1.3 mL. Among them, 81 of 331 (24.5%) had Gleason grade 4/5 disease postoperatively. Patients were stratified into two groups: (1) TV less than 0.5 mL, using the classical definition; and (2) TV between 0.5 mL and 1.3 mL, using the range of updated definition. We compared biochemical recurrence (BCR)-free survival and identified independent predictors of BCR in each group.Results:Group 2 had more Gleason grade 4/5 disease than group 1 (P<0.001). On multivariate analysis, Gleason grade 4/5 disease was not associated with BCR in group 1 (P=0.132). However, it was an independent predictor for BCR in group 2 (P=0.042). BCR-free survival were not significantly different according to the presence of Gleason grade 4/5 disease in group 1 (P=0.115). However, in group 2, it was significantly different according to the presence of Gleason grade 4/5 disease (P=0.041).Conclusions:Although the TV thresholds of the two definitions of IPC vary only slightly, this difference was enough to result in different clinical course if Gleason grade 4/5 disease was present. Therefore, the updated IPC TV threshold should be carefully applied as clinical parameter for active surveillance.

Prediction of Extraprostatic Extension in Patients with Clinically Organ-Confined Prostate Cancer

Introduction: Preoperative parameters for predicting extraprostatic extension (ECE) in clinically organ-confined prostate cancer patients are not well defined. Our aim was to evaluate the roles of the biopsy Gleason score, prostate-specific antigen (PSA)-based parameters, volume, and clinical T classification in prediction of ECE. Materials and Methods: A total of 188 patients with clinically organ-confined prostate cancer who underwent radical prostatectomy from January 1998 to December 2007 were included in the study. Age, prostate volume, preoperative total serum PSA (tPSA), free PSA, PSA density (PSAD), biopsy Gleason score, and clinical T classification were analyzed by univariate and multivariate analyses to predict ECE. Results: Pathologic examination revealed 130 patients had organ-confined disease and 58 patients were positive for ECE. Multivariate logistic regression analyses showed that tPSA was an independent predictor of ECE. Gleason score ≥8 had a trend for predicting ECE. Receiver operating characteristic (ROC) curves suggested that tPSA and PSAD had a similar diagnosis performance in the whole cohort. For patients with Gleason score of 7, PSAD was found to be statistically better than tPSA for predicting ECE. Conclusions: tPSA remains one of the most important factors for predicting ECE in prostate cancer patients. PSAD may be more helpful than tPSA for predicting ECE in the patients with Gleason score of 7.

Abstract 4827: Does beam radiation treatment of prostate cancer increase rectal cancer risk.

Abstract Background: Prostate cancer (PC) is the most common invasive cancer among US men. The majority of PCs are organ-confined at diagnosis and are candidates for treatment using external beam radiation alone (RAD), prostatectomy alone (SURG), or other protocols. This research was conducted at Loma Linda University using California Cancer Registry (CCR) population-data for 1988-2010. The CCR is part of the Surveillance Epidemiology and End Results (SEER) program. Since 1988, there has been mandatory state-wide reporting of information for all invasive cancers to the CCR including cancer diagnosis and stage, treatment, and demographic characteristics, with greater than 99% case reporting. From 1988-2010, nearly half a million California men were diagnosed with prostate cancer (PC). The majority were organ-confined at diagnosis. Problem: We sought to assess whether RAD treatment of prostate cancer, that exposes peri-rectal tissue to ionizing radiation, was followed by increased risk of rectal cancer, relative to SURG. Methods: We conducted record linkage for all new prostate and rectal (rectum and rectosigmoid junction) cancers in California 1988-2010, identifying men diagnosed with rectal cancer 5+ years following RAD or SURG treatment of organ-confined prostate. Among the men treated with RAD vs SURG, the Cox proportional hazards ratio (HR) for rectal cancer was assessed. Demographic covariates included: age (&amp;lt;50, 50-74, &amp; 75+ years), race/ethnicity as Asian/Other (A-O), non-Hispanic black (NHB), Hispanic (Hisp), and non-Hispanic white (NHW), and socioeconomic status quintiles (1-5 Highest) . Results: There were 194 new rectal cancers among 54,130 PC cases that had been treated with RAD and 254 cases among 69,105 SURG patients. Adjusting for demographic covariates and year of PC diagnosis, the rectal cancer HR with 95% CI for RAD vs. SURG was: HRRAD/SURG=1.58, 95% CI=1.28-1.94. Following are HRs for age (continuous variable) (HRAge=1.02, 95% CI=1.00-1.34) and categories of race/ethnicity (HRA-O/NHW=0.99, 95% CI=0.66-1.49; HRNHB/NHW=1.09, 95% CI=0.75-1.57; HRHisp/NHW=1.07, 95% CI=0.78-1.47); SES (HRSES1/SES5=0.92, 95% CI=0.64-1.34; HRSES2/SES5=1.17, 95% CI=0.87-1.57; HRSES3/SES5=1.20, 95% CI=0.92-1.57; HRSES4/SES5=1.19, 95% CI=0.93-1.54); and PC diagnostic year (continuous variable) (HRYear=0.94, 95%CI=0.92-0.97). Discussion/Conclusions: Findings reveal increased rectal cancer hazards among organ-confined prostate cancer patients treated with RAD, relative to SURG, that is substantially independent of demographic covariates. Treatment of rectal cancer among PC patients treated with RAD is further complicated because they may have already received maximum pelvic RAD dose. Further analyses that seek to distinguish roles of different dose and delivery methods for RAD are ongoing. Citation Format: John W. Morgan, Brice Jabo, Mark Ghamsary, David Bush. Does beam radiation treatment of prostate cancer increase rectal cancer risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4827. doi:10.1158/1538-7445.AM2013-4827

Anxiety, depression, sexual dysfunction and quality of life in prostate cancer based on stage of the disease

Background: Prostate cancer is common in men and in many studies quality of life, mental health problems and sexual dysfunction were examined in this population. However, there are relatively few studies examining the impact of the disease according to the stages. In this study we aimed to compare the levels of anxiety, depression, quality of life and sexual dysfunction of the prostate cancer patients according to their stages. Method: 80 patients with prostate cancer who applied to urology outpatient clinic were enrolled to the study. Patients were divided into three groups according to their stages; localized/organ-confined, local spread and metastatic spread. Short Form 36 (SF-36), Hospital Anxiety and Depression Scale (HAD) and the Arizona Sexual Experience Scale (ASEX) were performed. Results: According to the stage of prostate cancer, physical functioning subscale of quality of life was significantly lower in patients with metastatic prostate cancer than in patients with organ-confined prostate cancer (F= 4.53, p= 0.014). There were no associations between anxiety and depression scores and the stage of prostate cancer. Sexual desire was better in organ-confined prostate cancer patients compared to metastatic prostate cancer patients (F= 5.32, p= 0.007). Conclusion: The patients with prostate cancer might have different levels of physical functioning and sexual aversion problems at different stages of the disease. The clinicians should consider these two issues during follow-up of these patients.

Cyr61 is regulated by cAMP‐dependent protein kinase with serum levels correlating with prostate cancer aggressiveness

Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. Previously, we demonstrated that Cyr61 was highly expressed in prostate cancer (PCa) but that the expression levels were associated with a lower risk of PCa recurrence. In the present study, we demonstrate that serum Cyr61 is a potential biomarker that correlates with PCa aggressiveness. Furthermore, we also explore the potential mechanism underlying the changes in Cyr61 expression during PCa progression. Cyr61 concentrations in the medium from PCa cell lines and in serum samples obtained from PCa patients were measured by sandwich ELISA. Serum Cyr61 levels were correlated with disease characteristics and the association between Cyr61 expression changes by several types of stimulation or stress and cAMP/cAMP-dependent protein kinase (PKA) pathway were examined. There was a positive correlation between Cyr61 levels in cell supernatants and mRNA expression in these cell lines. Serum Cyr61 levels were significantly higher in non-organ-confined PCa patients (116.3 ± 140.2 ng/ml) than in organ-confined PCa patients (79.7 ± 56.1 ng/ml) (P = 0.031). Cyr61 expression was up-regulated in response to both lysophosphatidic acid and androgen treatments which promoted PCa cell invasion. Serum starvation and phosphoinositide-3-kinase inhibition also resulted in Cyr61 up-regulation; however, they suppressed cell proliferation. Cyr61 up-regulation was correlated with an increase in cAMP and suppressed by PKA inhibition. These findings suggest that Cyr61 expression in PCa is regulated by the cAMP/PKA pathway and that circulating Cyr61 levels are a potential serum-based biomarker for characterizing PCa.

Advances in the study of the peripheral nervous system for erection in animals and humans.

Since Walsh first emphasized the importance of preserving the neurovascular bundle n to protect the cavernous nerve during pelvic surgery, patients' sexual life quality has dramatically improved. Today, nerve-sparing radical prostatectomy is the established gold standard for organ-confined prostate cancer patients. Recent technical advances in functional assessment such as intraoperative electrical stimulation have unveiled new anatomical features and physiological roles. Basic research has advanced understanding of cavernous nerve function, while molecular biology has uncovered the crucial role of neuronal nitric oxide in mediating erection, and has led to new treatments such as phosphodiesterase type-5 inhibitors. A recent focus in cavernous nerve research concerns the nerve distribution external to the neurovascular bundle. The cavernous nerves in humans appear to be distributed more widely beneath the lateral pelvic fascia than in other animals, and electrical stimulation studies suggest possible involvement of these nerves in erection. These findings have prompted new surgical techniques such as the "veil of Aphrodite", or "intrafascial nerve-sparing" procedures. These recent anatomical and physiological studies in humans and animals and their impact are reviewed in this article. Further investigation should stimulate future advances in strategies to preserve erectile function in RP patients.

Stereotactic body radiotherapy for treatment of organ-confined prostate cancer: Efficacy and quality of life at 4 years.

88 Background: The purpose of this study is to assess the efficacy and toxicity of stereotactic body radiotherapy for organ confined prostate cancer patients. Methods: Fifty T1cN0M0 prostate carcinoma patients (42 low- and 8 intermediate-risk) received 5 fractions of 7 Gy SBRT with Cyberknife to a total dose of 35 Gy delivered over 5 consecutive days. Mean patient age was 69.5 years and mean pre-treatment PSA was 5.7 ng/mL. All patients received 1500 mg of amifostine intrarectally prior to each SBRT fraction. Patients were treated to the 83%-87% contour line with 5-mm margins added to the gross tumor volume at all borders except for the rectum where a 3-mm margin was added. During treatment, 4 gold fiducial seeds were continuously tracked. Toxicity was assessed using the Radiation Therapy Oncology Group toxicity scale; biochemical failure was assessed by the Phoenix criteria, and quality of life was assessed with the Expanded Prostate Cancer Index Composite Questionnaire (EPIC). Results: At a median follow-up of 48 months (range, 46-53 months) one biochemical failure has occurred. Three patients died of intercurrent disease. The median PSA at 48 months is 0.10 ng/mL (range, 0.01-3.5 ng/mL). At 42 months, 42 of 47 patients had achieved a PSA of 0.5 ng/mL or less. Toxicity has been minimal with no grade 3+ toxicities. Actuarial 48 month rates for grade 2 urinary and rectal toxicity-free survival were 95.5% and 97.8%, respectively. Mean EPIC bowel and urinary quality of life returned to baseline by 18 months and remain at baseline values at 36 months. Of the 36 patients that were potent prior to treatment 29 (80.5%) maintained potency. Conclusions: At 48 months median follow-up the promising biochemical control, minimal toxicity and the promising potency preservation rates are highly encouraging. [Table: see text]

700 DIRECT EVIDENCE THAT VISCERAL FAT RATIO AFFECTS THE BASELINE ERECTILE FUNCTION AMONG THE RADICAL PROSTATECTOMY PATIENTS

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2010700 DIRECT EVIDENCE THAT VISCERAL FAT RATIO AFFECTS THE BASELINE ERECTILE FUNCTION AMONG THE RADICAL PROSTATECTOMY PATIENTS Motoi Takeuchi, Shin-ichi Hisasue, Kohei Hashimoto, Ryoji Furuya, Akihiko Iwasawa, Keishi Ogura, Yu-ki Kyoda, Khoji Ichihara, Naoya Masumori, and Taiji Tsukamoto Motoi TakeuchiMotoi Takeuchi More articles by this author , Shin-ichi HisasueShin-ichi Hisasue More articles by this author , Kohei HashimotoKohei Hashimoto More articles by this author , Ryoji FuruyaRyoji Furuya More articles by this author , Akihiko IwasawaAkihiko Iwasawa More articles by this author , Keishi OguraKeishi Ogura More articles by this author , Yu-ki KyodaYu-ki Kyoda More articles by this author , Khoji IchiharaKhoji Ichihara More articles by this author , Naoya MasumoriNaoya Masumori More articles by this author , and Taiji TsukamotoTaiji Tsukamoto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1141AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metabolic syndrome is a cluster of cardio-metabolic risk factors including visceral fat accumulation, dyslipidemia, hyperglycemia and hypertension. It is also associated with erectile dysfunction in aged male. We investigated the impact of visceral fat measured with the computed tomography (CT) on the baseline erectile function in the radical prostatectomy patients. METHODS We reviewed 74 of 178 organ confined prostate cancer patients who underwent radical prostatectomy between 2005 and 2009 in our institution. The patients whose preoperative CT was available were included, and those who had any kind of testosterone ablation were excluded. We measured both area of the visceral fat and the subcutaneous fat at the level of the umbilicus from abdominal CT and calculated the visceral fat ratio. Erectile function was assessed by IIEF5 and maximum penile circumferential change (MPCC) during a night. RESULTS Median age was 66 years and median visceral fat ratio was 51.8% (range 20.3-72.4). Median IIEF5 score was 15 and median MPCC was 2.6cm (range 0.4-5.0). We investigated the relationship between the visceral fat ratio and erectile function, and there was no significant difference in the IIEF5 score, but 75‰ of MPCC (3.25cm) showed the significant difference in the univariate analysis. We carried out the multivariate analysis using parameters which were selected as risk factors for erectile dysfunction including age, smoking, hypertension, diabetes, BMI and visceral fat ratio. It revealed that a single predictor for the baseline erectile function was visceral fat ratio (p=0.04). The median visceral fat ratio was significantly higher in the MPCC < 3.25cm group (52.4%) than ≥ 3.25cm group (49.9%). (p=0.04, Fig. 1) CONCLUSIONS This is the first study which suggested the impact of the visceral fat accumulation on the erectile function. The further study will be necessary to clarify the influence of the visceral fat ratio on the recovery of erectile function following the radical prostatectomy. Sapporo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e273 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Motoi Takeuchi More articles by this author Shin-ichi Hisasue More articles by this author Kohei Hashimoto More articles by this author Ryoji Furuya More articles by this author Akihiko Iwasawa More articles by this author Keishi Ogura More articles by this author Yu-ki Kyoda More articles by this author Khoji Ichihara More articles by this author Naoya Masumori More articles by this author Taiji Tsukamoto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serum Adipocytokine Levels in Prostate Cancer Patients

Introduction: We estimated the circulating levels of adipocytokines such as adiponectin and leptin in nonobese nondiabetic prostate cancer (PCa) patients and compared the results with controls and benign prostate hyperplasia (BPH) patients. Material and Methods: Fifty patients with PCa, 20 patients with BPH and 50 healthy volunteers were entered into the study. Their blood samples were investigated for adipocytokines with the ELISA method. Results: Adiponectin levels were determined as 8.9 and 5.5 μg/ml for the same patients. Leptin concentration was 14.78 ng/ml in organ-confined PCa patients, and 15.24 ng/ml in advanced PCa patients. In control patients, adiponectin and leptin levels were 18.4 and 12.98 ng/ml, respectively. Conclusion: Serum adipocytokine levels of PCa patients were significantly different from those of controls and BPH patients who were not obese or diabetic. Therefore, further molecular investigation of these adipocytokines will help understand the mechanism.

Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study

In clinically organ-confined prostate cancer patients, bloodstream tumour cell dissemination generally occurs, and may be enhanced by surgical prostate manipulation. To evaluate cancer-cell seeding impact upon patient recurrence-free survival, 155 patients were prospectively enrolled then followed. Here, 57 patients presented blood prostate cell shedding preoperatively and intraoperatively (group I). Of the 98 preoperatively negative patients, 53 (54%) remained negative (group II) and 45 (46%) became intraoperatively positive (group III). Median biological and clinical recurrence-free time was far shorter in group I (36.2 months, P<0.0001) than in group II (69.6 months) but did not significantly differ in group II and III (69.6 months vs 65.0). Such 5-year follow-up data show that preoperative circulating prostate cells are an independent prognosis factor of recurrence. Moreover, tumour handling induces cancer-cell seeding but surgical blood dissemination does not accelerate cancer evolution.

Antibody and T‐cell responses specific for the androgen receptor in patients with prostate cancer

The androgen receptor (AR) is a steroid hormone receptor that is an essential regulator of prostate development, and the primary molecular target for the treatment of metastatic prostate cancer. In this report, we evaluated whether patients with prostate cancer have pre-existing immune responses specific for the AR as evidence that the AR also might be pursued as an immunological target antigen. The detection of auto-antibodies specific for the AR in patient sera was evaluated by ELISA and Western blotting. Peripheral blood mononuclear cells were analyzed for the presence of AR-specific T-cells, as measured by T-cell proliferation, interferon gamma (IFNgamma) and interleukin-10 secretion. We found that a significantly higher frequency of prostate cancer patients have AR LBD-specific antibody responses than do healthy male volunteers [18/105 cancer patients (17.1%) vs. 0/41 healthy volunteers, P = 0.0049], and that these responses were present regardless of the patients' disease stage [8/46 organ-confined prostate cancer patients (17.4%), 3/22 metastatic androgen-dependent patients (13.6%), and 7/37 metastatic, androgen-independent patients (18.9%)]. These antibodies were pre-dominantly of the IgG isotype, and furthermore of the IgG(2) sub-isotype. In addition, we found that patients with antibody responses also had concurrent antigen-specific CD4+ and CD8+ T-cell proliferation and IFNgamma secretion when compared to patients without antibody responses. These data demonstrate that some patients with prostate cancer have pre-existing humoral and cellular immune responses specific for the AR, suggesting that tolerance against the AR is not absolute and that the AR may be a potential immunotherapeutic target antigen.

Combined modality staging of prostate carcinoma and its utility in predicting pathologic stage and postoperative prostate specific antigen failure

Objectives This study was performed to predict the factors that can optimize preoperative staging for clinically localized prostate cancer patients. Methods Logistic and Cox regression multivariable analyses were performed on 480 surgically-managed prostate cancer patients to evaluate the ability of clinical stage, prostate specific antigen (PSA), biopsy Gleason sum, percent positive biopsies, and endorectal coil magnetic resonance imaging (erMRI) results to predict for pathologic established extracapsular extension (ECE), seminal vesicle invasion (SVI), and time to postoperative PSA failure. Results The characteristics of clinically organ-confined prostate cancer patients at high risk (>67%) for postoperative PSA failure within 3 years include: (A) PSA >20 ng/mL; (B) Biopsy Gleason sum ≥8; or (C) erMRI positive for extraprostatic disease and intermediate risk disease. For patients at intermediate risk (ie, either a PSA <4 and biopsy Gleason sum of 7; PSA >4 to 10 ng/mL and biopsy Gleason sum 5 to 7; or a PSA > 10 to 20 ng/mL and biopsy Gleason sum 2 to 7), despite 100% positive biopsies, 50% of patients had pathologic organ-confined disease. However, in the subset of intermediate-risk patients with a positive erMRI for either ECE or SVI and at least 50% positive biopsies, all had extraprostatic disease and failed biochemically by 47 months postoperatively. Intermediate-risk patients with <50% positive biopsies had pathologic organ-confined disease in at least 77% of the cases. Conclusions Combined modality staging using the PSA, biopsy Gleason sum, percent positive biopsies, and endorectal coil MRI findings in select patients can predict pathologic stage and postoperative PSA failure. Therefore, this combined modality staging may optimize patient selection for phase 3 trials examining the role of neoadjuvant androgen ablative therapy for patients with clinically localized disease.