Gleason Sum Score Research Articles

前立腺全摘除術における閉鎖リンパ節転移陽性部位の検討

In this study, we assessed the significance of complete dissection of the dorsal lymph node of the obturator nerve during radical prostatectomy. Fifty-six patients undergoing open radical prostatectomy and pelvic lymph node dissection for treatment of prostate cancer were included in this study. Neoadjuvant hormonal therapy and radiation therapy were not performed in any of the patients. First, pelvic lymph node dissection was performed between the external iliac vein and obturator nerve and classified as "ventral lymph node of the obturator nerve". Then, the tissue located in the area between the obturator nerve and the surface of the obturator internus muscle was removed and classified as "dorsal lymph node of the obturator nerve". Both lymph nodes were meticulously examined by identical pathologist. Lymph node yields, lymph node positive rate, and the factors associated with lymph node metastasis were studied. Eight of the 56 patients had pelvic lymph node metastases (6 were high risk and 2 were intermediate risk according to the D'Amico's criteria). In the 8 node-positive patients, only 1 patient had positive lymph node in "ventral lymph node of the obturator nerve" exclusively. Four patients had positive lymph node exclusively in "dorsal lymph node of the obturator nerve" and 3 patients had in both "ventral and dorsal lymph nodes of the obturator nerve". The total lymph node yields from "ventral lymph node of the obturator nerve" and "dorsal lymph node of the obturator nerve" were 459 (8.2 per patient) and 117 (2.1 per patient), respectively. The total numbers of positive lymph nodes from "ventral lymph node of the obturator nerve" and "dorsal lymph node of the obturator nerve" were 6 and 12, respectively. Lymph node positive rate was significantly higher in "dorsal lymph node of the obturator nerve" (10%) than "ventral lymph node of the obturator nerve" (1.3%) (P < 0.0001). The level of prostate-specific antigen (> or = 20 ng ml), Gleason score sum at prostate biopsy (> or = 9), and lymph node yield (> or = 16) were associated with lymph node status on univariate analysis. In multivariate analysis, only lymph node yield was associated with lymph node status. Dorsal lymph nodes of the obturator nerve should be dissected completely during radical prostatectomy.

Validation of copy number variants associated with prostate cancer risk and prognosis

ObjectiveTwo recent studies have reported novel heritable copy number variants on chromosomes 2p, 15q, and 12q to be associated with prostate cancer (PCa) risk in non-Hispanic Caucasians. The goal of this study was to determine whether these findings could be independently confirmed in the Caucasian population from the South Texas area. Methods and materialsThe study subjects consisted of participants of the San Antonio Biomarkers of Risk for PCa cohort and additional cases ascertained in the same metropolitan area. We genotyped all 7 of the reported copy number variants using real-time quantitative polymerase chain reaction in 1,536 (317 cases and 1,219 controls) non-Hispanic Caucasian men, and additionally, we genotyped 632 (191 cases and 441 controls) Hispanic Caucasian men for one of these variants, a deletion on 2p24.3. ResultsAssociation of the deletion on 2p24.3 with overall PCa risk did not meet our significance criteria but was consistent with previous reports (odds ratio, 1.40; 95% confidence interval 0.99–2.00; P = 0.06). Among Hispanic Caucasians, this deletion is much less prevalent (minor allele frequencies of 0.059 and 0.024 in non-Hispanic and Hispanic Caucasians, respectively) and did not show evidence of association with risk for PCa. Interestingly, among non-Hispanic Caucasians, carrying a homozygous deletion of 2p24.3 was significantly associated with high-grade PCa as defined by Gleason score sum ≥8 (odds ratio, 27.99; 95% confidence interval 1.99–392.6; P = 0.007 [the Fisher exact test]). The remaining 6 copy number variable regions either were not polymorphic in our cohort of non-Hispanic Caucasians or showed no evidence of association. ConclusionsOur findings are consistent with the reported observation that a heritable deletion on 2p24.3 is associated with PCa risk in non-Hispanic Caucasians. Additionally, our observations indicate that the 2p24.3 variant is associated with risk for high-grade PCa in a recessive manner. We were unable to replicate any association with PCa for the variants on chromosomes 15q and 12q, which may be explained by regional population differences in low frequency variants and disease heterogeneity.

The “PROCAINA (PROstate CAncer INdication Attitudes) Project” (Part II) — A survey among Italian radiation oncologists on radical radiotherapy in prostate cancer

Radiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT. During the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/- hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique, type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed. Three hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation. Despite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto-date, detailed, and evidence-based recommendations.

1482 FACTORS FOR PREDICTION OF GLEASON SCORE UPGRADING AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Detection & Screening (II)1 Apr 20131482 FACTORS FOR PREDICTION OF GLEASON SCORE UPGRADING AFTER RADICAL PROSTATECTOMY Ching-Wei Yang, Tzu-Ping Lin, Yi-Hsiu Huang, Hsiao-Jen Chung, Junne-Yih Kuo, William Huang, Howard Wu, Yen-Hwa Chang, Alex Lin, and Kuang-Kuo Chen Ching-Wei YangChing-Wei Yang Taipei, Taiwan More articles by this author , Tzu-Ping LinTzu-Ping Lin Taipei, Taiwan More articles by this author , Yi-Hsiu HuangYi-Hsiu Huang Taipei, Taiwan More articles by this author , Hsiao-Jen ChungHsiao-Jen Chung Taipei, Taiwan More articles by this author , Junne-Yih KuoJunne-Yih Kuo Taipei, Taiwan More articles by this author , William HuangWilliam Huang Taipei, Taiwan More articles by this author , Howard WuHoward Wu Taipei, Taiwan More articles by this author , Yen-Hwa ChangYen-Hwa Chang Taipei, Taiwan More articles by this author , Alex LinAlex Lin Taipei, Taiwan More articles by this author , and Kuang-Kuo ChenKuang-Kuo Chen Taipei, Taiwan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2947AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gleason score upgrading after radical prostatectomy existed in a significant portion of patients who were diagnosed prostate cancer by needle biopsy and may has untoward effect regarding treatment outcomes. We identified clinical and pathological parameters that predict pathological upgrading in this population. METHODS A total of 324 patients who underwent biopsy and radical prostatectomy between March 2000 and September 2011 were included in the study. Clinical Gleason score upgrading was defined as higher Gleason score sum in prostatectomy than in needle biopsy specimen pathologically. Pretreatment characteristics were analyzed to identify predictors of pathological upgrading. Upgrading significance was established in cases that were and were not upgrade. RESULTS A total of 125 patients (38 %) had upgraded and 199 patients (62 %) had non-upgraded Gleason score postoperatively. Preoperative serum prostate specific antigen (PSA) greater than 12ng/ml (p = 0.008) and prostate specific antigen density (PSAD) greater than 0.35 (p = 0.04) was associated with pathological upgrading. Prostate specific antigen, prostate volume, biopsy number, biopsy cores, positive biopsy side, number of positive cores, highest tumor percentage of positive cores, interval to surgery, methods of operation and different operators were not associated with upgrading. Higher PSAD, number of positive cores and tumor percentage of positive cores were associated with pathologically extraprostatic extension or positive surgical margin while Gleason score upgrading were not significant difference associated with extraprostatic extension or positive surgical margin in prostatectomy specimens. CONCLUSIONS Higher serum PSA and PSAD predict clinically significant upgrading in prostate cancer patients who were treated with radical prostatectomy. These parameters should be considered in the pretreatment risk assessment and counseling of prostate cancer patients. Table 1. Pre-RP predictors in upgrading and non-upgrading groups Predictors Upgrading (N=105) Non-upgrading (N=93) P value Mean age (y/o) 68 65 0.012 PSA (ng/ml) 14 11 0.280 Prostate volume (ml) 34 37 0.201 PSA density (ng/ml2) 0.46 0.36 0.128 Mean max% Ca in any core 49 36 0.007 Mean days from Biopsy to RP 55 61 0.117 Number of biopsies 1.1 1.1 0.930 Mean No. of biopsy cores 9.2 8.9 0.504 Mean No. of positive cores 2.8 1.9 0.004 Bx Primary GS 3.0 3.2 0.031 Bx Secondary GS 3.0 3.1 0.967 Bx GS sum 6.0 6.3 0.678 T test & Mann-Whitney test Table 2. Multivariate logistic regression analysis of Gleason Score upgrading after RP Predictors OR 95% CI P value PSA <>12 ng/ml 4.323 1.704 ∼10.967 0.002 PSA density > 0.35 ng/ml2 2.539 1.193∼5.406 0.016 Max Ca > 20% in any core 1.649 0.760∼3.578 0.206 Biopsy positive >2 cores 1.971 0.904∼4.296 0.088 T test & Mann-Whitney test © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e607-e608 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ching-Wei Yang Taipei, Taiwan More articles by this author Tzu-Ping Lin Taipei, Taiwan More articles by this author Yi-Hsiu Huang Taipei, Taiwan More articles by this author Hsiao-Jen Chung Taipei, Taiwan More articles by this author Junne-Yih Kuo Taipei, Taiwan More articles by this author William Huang Taipei, Taiwan More articles by this author Howard Wu Taipei, Taiwan More articles by this author Yen-Hwa Chang Taipei, Taiwan More articles by this author Alex Lin Taipei, Taiwan More articles by this author Kuang-Kuo Chen Taipei, Taiwan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy

Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥ 8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥ 0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥ 2 predictors, respectively. In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies.

Second to fourth digit ratio: its relationship with core cancer volume and Gleason score in prostate biopsy

To investigate the relationships between 2nd to 4th digit ratio (digit ratio) and prostate cancer detection rate and biopsy findings, including Gleason score. In 770 consecutive men aged 40 years or older that presented with lower urinary tract symptoms (LUTS), right hand 2nd and 4th digit lengths were measured prior to PSA determinations, DRE and transrectal ultrasonography (TRUS). Among these, 166 men with a prostate specific antigen (PSA) level ≥ 3 ng/mL or abnormal digit rectal examination (DRE) prospectively underwent prostate biopsies. The relationship between digit ratio and prostate cancer detection rate and biopsy findings was investigated. The study subjects were allocated to two groups by digit ratio (group A: digit ratio < 0.95; n = 420; group B: digit ratio ≥ 0.95; n = 350). Despite similar biopsy rates (22.4% vs. 20.6%, p = 0.544), group A had higher cancer detection rate (46.8% (44/94) vs. 23.6% (17/72), p = 0.002; OR = 2.847, 95% CI = 1.445-5.610). When we analyzed 408 positive biopsy cores (group A: digit ratio < 0.95, n = 282; group B: digit ratio ≥ 0.95, n = 126), group A had higher percentage of core cancer volume (46.7% vs. 37.1%, p = 0.005) and more biopsy cores with high Gleason score (sum of Gleason score ≥ 9: 18/282 (6.4%) vs. 1/126 (0.8%), p = 0.010; primary Gleason score = 5: 12/282 (4.3%) vs. 0/126 (0.0%), p = 0.021). A lower digit ratio is related to an increased detection rate of prostate cancer, a high percentage of core cancer volume and a high Gleason score.

Prostate Cancer Incidence in Patients on 5α-Reductase Inhibitors for Lower Urinary Tract Symptoms: A 14-Year Retrospective Study

There is still much debate regarding the long-term effect of 5α-reductase inhibitors (5-ARI) on the development of prostate cancer (PC). We tested the incidence of prostate cancer and the tumour Gleason grading in a non-screened population who were prescribed 5-ARIs for lower urinary tract symptoms (LUTS). Data from a prostatic biopsy database were analysed in a retrospective study, and included a period of 14 years (01/01/1997 to 01/01/2011). Those patients who were on 5-ARIs with either finasteride or dutasteride for less than 1 year were excluded. Patients who presented with LUTS and underwent diagnostic prostatic biopsies were included in this study. This patient cohort was further categorised according to their history of 5-ARIs medication. The incidence of PC in the 5-ARI treated group was 15.4% ( n = 22/143), comparable to that of the untreated group (16.7%, n = 332/1990) ( p = 0.7318). Mean Gleason sum score and respective grade was the same (7 = 3 + 4) (median sum score 7 (range 6–10)). Average age at the time of PC diagnosis was similar regardless of 5-ARIs treatment: 72 (range 50–84) and 73 (45–84) years for treated and untreated groups, respectively. In this retrospective study, patients treated with 5-ARIs for LUTS had similar risk in developing PC when compared to those who did not receive 5-ARIs. The Gleason sum scores for the cancers were similar in the two groups.

Distinct expression and activity of GSK‐3α and GSK‐3β in prostate cancer

Glycogen synthase kinase (GSK-3) is upregulated in many types of tumor, including prostate cancer. GSK-3 inhibitors reduce prostate tumor cell growth; however, it is not clear if both isoforms, GSK-3α and GSK-3β, are involved. Here, we compared their expression in prostate tumors and used gene silencing to study their functions in 22Rv1 prostate cancer cells. Compared to normal prostate, GSK-3α and GSK-3β were upregulated in 25/79 and 24/79 cases of prostate cancer, respectively, with GSK-3α elevated in low Gleason sum score tumors and GSK-3β expressed in high Gleason tumors, and both isoforms correlating with high expression of the androgen receptor (AR). Gene silencing of GSK-3α and, to a lesser extent, GSK-3β reduced AR transcriptional activity. In addition, silencing of GSK-3β, but not GSK-3α, reduced Akt phosphorylation. Acute and chronic silencing of either isoform reduced 22Rv1 growth in colony formation assays; however, this did not correlate with effects on AR activity. The GSK-3 inhibitor CHIR99021 reduced 22Rv1 colony formation by 50% in normal growth medium and by 15% in hormone-depleted medium, suggesting that GSK-3 is required both for hormone-dependent and hormone-independent proliferation. In addition, CHIR99021 enhanced growth inhibition by the AR antagonists bicalutamide and MDV3100. Finally, expression of GSK3A and GSK3B mRNAs correlated with a gene expression signature for androgen-regulated genes. Our observations highlight the importance of the GSK-3/AR signaling axis in prostate cancer and support the case for development of isoform-specific GSK-3 inhibitors and their use, in combination with AR antagonists, to treat patients with prostate cancer.

Intraoperative cell salvage in radical prostatectomy does not appear to increase long‐term biochemical recurrence, metastases, or mortality

Blood management strategies help to conserve allogeneic red blood cells, a finite resource. Intraoperative cell salvage (ICS) is an effective method of allogeneic avoidance. However, concerns persist about the safety of ICS in surgical oncology cases, including radical prostatectomy (RP). Previous findings do not support these concerns. We hypothesized that ICS would not increase rates of long-term prostate cancer recurrence characterized by biochemical failure, disease dissemination, or mortality. Consecutive patients undergoing RP by a single urologist over two 3-month periods 1 year apart were analyzed retrospectively. Patients in the first period had preoperative autologous donation (PAD) but not ICS (PAD group), whereas those in the second period had ICS only (ICS group). Variables assessed included patient demographics, prostate-specific antigen levels at surgery and end of follow-up, clinical stage, operative time, surgical margin status, pathologic stage and grade, Gleason score sum, length of hospital stay, biochemical recurrence, metastases, and mortality. A total of 116 consecutive patients were analyzed. Of these, 32 patients in the PAD group and 42 patients in the ICS group had follow-up of at least 4.75 years. There was a significantly higher rate of biochemical failure (34.4% vs. 9.5%; p = 0.02) and metastases (12.5% vs. 0%; p = 0.03) in the PAD group versus the ICS group; there was no significant difference in mortality (9.4% vs. 0%; p = 0.08). ICS appears to be a safe and effective method of allogeneic blood conservation in patients undergoing RP. The findings suggest that there is no increased risk of biochemical failure, disease dissemination, or mortality at 5 years post-RP as a result of ICS use.

Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

BackgroundProstate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value.Methodology/Principal FindingsWe first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7–8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men.Conclusion/SignificanceSPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA.

Phase II Study of Long-Term Androgen Suppression With Bevacizumab and Intensity-Modulated Radiation Therapy (IMRT) in High-Risk Prostate Cancer

We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.

Measuring interobserver variation in a pathology EQA scheme using weighted κ for multiple readers

BackgroundA Urological Pathology External Quality Assurance (EQA) Scheme in the UK has reported observer variation in the diagnosis and grading of adenocarcinoma in prostatic biopsies using basic κ statistics, which...

Impact of HMG-CoA Reductase Inhibitor (Statin) Use on Blood Loss During Robot-Assisted and Open Radical Prostatectomy

In addition to their lipid lowering effects, HMG-CoA reductase inhibitors (statins) have been shown to exert antithrombotic effects through downregulation of the coagulation cascade. Because statin use is widespread, it is important to understand the impact of these drugs on blood loss (BL) during surgery. We studied the impact of statin use on BL during robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP). A retrospective review was conducted of a database approved by the Institutional Review Board for patients who underwent RARP or ORP at a single academic institution. Patients were categorized as statin-users or statin-naïve at the time of surgery. Patient demographic information was recorded as was perioperative data, including preoperative and postoperative hematocrit (Hct) value. BL was defined as % Hct change presurgery vs postsurgery. In addition, the outcome of ≥10% drop in Hct was studied. The t test and chi-square analysis were used to compare variables across statin use groups. Univariate and multivariable logistic regression analyses were used to identify factors that impacted BL. From 1987 to 2010, 3578 patients underwent prostatectomy for prostate cancer (RARP=945 and ORP=2633). Of these, 676 men were identified as statin-users and 2902 as statin-naïve. Mean patient age was 60.2±7.0 years. Statin-users were found to be older (P<0.001), have lower mean preoperative prostate-specific antigen (PSA) levels (P=0.002), and have higher pathologic Gleason sum scores (P<0.001). For ORP, statin use was associated with increased BL with Hct % change of 20.7% for users vs18.6% for nonusers, (P<0.001). For RARP, no significant change in Hct was seen with statin use with % changes of 12.6% and 12.5%, respectively (P=0.9). When controlling for age, Gleason sum, surgeon, date of surgery and PSA level, statin use was associated with increased BL (P=0.04). Even when controlling for age, Gleason sum, surgeon, date of surgery, and PSA, statin use is associated with increased BL during RP. This information may impact preoperative planning and patient counseling for men who are taking statins while preparing for RP.

Evaluation of global DNA hypomethylation in human prostate cancer and prostatic intraepithelial neoplasm tissues by immunohistochemistry

ObjectiveTo identify the differences of 5-methylcytosine (5-MC) level between primary prostate cancer tissues (PCTs), prostate cancer-adjacent benign tissues (PCABTs), low-grade prostatic intraepithelial neoplasia (LGPIN), and high-grade prostatic intraepithelial neoplasia (HGPIN), and further analysis the 5-MC alterations in prostate cancer with pathologic grade and clinical prognosis. Materials and methodsImmunohistochemistry method with a 5-MC monoclonal antibody was used to identify the 5-methylcytosine (5-MC) levels in PCTs, PCABTs, LGPIN, and HGPIN specimens in the present study. Statistical analysis with SPSS software (SPSS Inc., Chicago, IL) was used to compare differences of 5-MC levels in the four groups and evaluate the 5-MC alterations in prostate cancer with pathologic grade and clinical prognosis. ResultsWe found that 38 of 48 (79.1%) patients studied showed a decrease in 5-MC staining of PCTs compared with PCABTs. The difference in the methylation levels for the PCTs and the PCABTs was highly statistically significant (P < 0.001). Spearman correlation showed there was no statistically significant association between the average score of 5-MC staining and Gleason score sum. Kaplan-Meier survival analysis showed that patient group with no or weak 5-MC staining compared with group with moderate and strong 5-MC staining was associated with better survival of patients, although there was no statistically significant difference between the 2 groups in predicating prognosis (P = 0.385). The average scores of 5-MC staining for LGPIN, HGPIN, PCABTs, and PCTs groups were 6.91, 1.58, 6.63, and 3.10, respectively. The methylation level of HGPIN group, as well as that of PCTs group, was significantly lower than those of LGPIN (P < 0.001; P < 0.001) and PCABTs groups (P < 0.001; P < 0.001), respectively, with the 5-MC levels of PCABTS group similar to that of LGPIN group (P = 0.476). 5-MC levels of HGPIN group was lower than that PCTs group (P = 0.004). ConclusionsWe found that global DNA methylation was low in most prostate cancer compared with benign regions from the same patient's sections. None of the DNA hypomethylation changes in primary cancers were associated with pathologic grade and clinical prognosis. In addition, immunohistochemistry showed that the global methylation was lower in HGPIN compared with LGPIN and methylcytosine staining in HGPIN was lower than that of PCTs. The results suggest that global DNA hypomethylation might play an important role in the process of prostate cancer initiation rather than progression.

Cancer control following focal prostate cryoablation for unilateral prostate cancer.

e15167 Background: Widespread use of PSA screening has resulted in earlier detection of prostate cancer, often in younger patients with small-volume, unilateral disease. Partial-gland cryoablation, sparing healthy tissue and the ipsilateral neurovascular bundle, is an attractive option for patients with unilateral cancer who wish to preserve erectile function and continence. We report our early cancer outcome data for focal prostate cryoablation. Methods: We performed a retrospective review from a single-institution IRB-approved cryotherapy database of over 900 patients. Inclusion criteria: unilateral prostate cancer treated with primary focal cryoablation. Exclusion criteria: prior or concurrent hormonal therapy. Disease-free survival at 3 and 5 years was calculated using the Kaplan-Meier method, and multivariate Cox regression models were performed to determine predictors of cancer outcome. Results: From 2002-2010, 102 men underwent primary focal cryoablation for prostate cancer. Mean age was 69.3 years (standard deviation [SD] 6.7 years); mean follow-up time 30.0 months (SD 24.2 months); mean pre-operative PSA 7.0 ng/mL (SD 5.5 ng/mL); and median Gleason score sum 6 (range 5-9). Overall mean post-treatment PSA nadir was 1.2 ng/mL (SD 1.3 ng/mL). Following treatment, 22 patients underwent transrectal ultrasound-guided (TRUS) biopsy for clinical suspicion of recurrent disease, and 10/22 (45%) had confirmed recurrent prostate cancer. No patients developed metastatic disease at any point during follow-up. On multivariate analysis, preoperative PSA level, preoperative Gleason score, number of positive biopsy cores, and total tumor length were all associated with disease recurrence. Conclusions: Early data show encouraging disease-free survival rates using follow-up TRUS biopsy results. Focal prostate cryoablation is a promising option for carefully selected patients, although further follow-up and long-term disease control will determine its role in prostate cancer treatment.

Presence of high grade tertiary Gleason pattern upgrades the Gleason sum score and is inversely associated with biochemical recurrence-free survival

ObjectivesTumor heterogeneity is a common finding and led to realization of a tertiary Gleason component (TGC) in prostate cancer. In an attempt to further investigate its prognostic value, we analyzed the association of tertiary Gleason pattern in Gleason score ≤ 7 tumors with pathologic stage and biochemical disease-free survival. Material and methodsA total of 331 radical prostatectomy specimens were analyzed retrospectively. The primary, secondary, and the tertiary patterns were evaluated by reviewing all of the pathologic slides. TGC was defined as Gleason grade pattern 4 or 5 for Gleason score < 7 tumors and Gleason grade pattern 5 for Gleason score 7 tumors. The pathologic prognostic factors, (extraprostatic extension, seminal vesicle and lymph node invasion, surgical margin status) of Gleason score < 7, 3+4, and 4+3 tumors with or without TGC were compared. Biochemical recurrence-free survival (BRFS) was calculated using Kaplan-Meier method with log rank test, and the influence of TGC was assessed in a Cox regression model. ResultsTGC observed more frequently with higher Gleason scores (21% of the GS < 7 cases, 23% of the GS 3+4 cases, and 58% of the GS 4+3 cases). In terms of adverse pathologic prognostic factors and BRFS, GS < 7 tumors with TGC behaved significantly worse than GS < 7 tumors without TGC (P = 0.01 and P = 0.001, respectively) with properties similar to GS 3+4 tumors without TGC. Gleason score 3+4 and 4+3 tumors without TGC were statistically similar and had better features than corresponding tumors of same Gleason score with TGC. Furthermore, Gleason score 7 tumors with TGC had similar features with GS 8–10 tumors. During follow-up, 73 (22%) subjects had PSA recurrence. In the Cox regression model TGC was an independent variable for BRFS (HR = 2.63, 95% CI = 1.39–4.98, P = 0.003). ConclusionAccording to the present study, 3 different prognostic groups were observed; good prognostic group: GS < 7, intermediate prognostic group: GS < 7+TGC, GS 3+4, and GS 4+3, and finally bad prognostic group: GS (3+4)+TGC, GS (4+3)+TGC, GS > 7. Presence of a TGC appears to upgrade the total score and adjuvant treatment decisions may further be refined by considering the tertiary pattern.

Cancer de la prostate localisé : l’IRM endorectale à 1,5 Tesla améliore-t-elle la sélection des patients en vue d’une surveillance active ?

To describe and assess MRI signs of significant tumor in a series of patients who all underwent radical prostatectomy and also fulfilled criteria to choose active surveillance according to French "SurAcaP" protocol.The clinical reports of 681 consecutive patients operated on for prostate cancer between 2002 and 2007 were reviewed retrospectively. All patients had endorectal MR (1.5 Tesla) with pelvic phased array coil. (1.5 T erMR PPA). Sixty-one patients (8.9%) fulfilled "SurAcaP" protocol criteria. Preoperative data (MR+core biopsy) were assessed by comparison to whole-mount step section pathology.85.3% of the 61 patients entering SurAcaP protocol had significant tumor at pathology. (Non Organ Confined Disease (Non OCD)=8.2%, Gleason sum score>6=39.2%). A new exclusion criterion has been assessed: T3MRI±NPS>1 as a predictor tool of significant tumor. ("T3MRI±NPS>1"=Non OCD at MR±number of positive sextants involved in tumor at MR and/or Core Biopsy > to 1). Sensitivity, specificity, PPV, NPV of the criterion "T3MRI±NPS>1" in predicting significant tumor were, respectively: 77%, 33%, 86%, 20%. Adding this criterion to other criteria of the "SurAcaP" protocol could allow the exclusion of all Non OCD, and a decrease in Gleason sum Score>6 rates (20%).Endorectal MR at 1.5 Tesla with pelvic-phased array coil should be considered when selecting patients for active surveillance in the management of prostate cancer. A criterion based upon MR and core biopsy findings, called "T3MR±NSP>1" may represent an exclusion citeria due to its ability to predict significant tumor.

Impact of Gleason score 4+3 on biochemical treatment failure in Japanese patients treated with monotherapeutic permanent interstitial brachytherapy.

e15108 Background: The permanent prostate brachytherapy (PPB) with iodine-125 seeds has an indication in patients with organ-confined prostate cancer. Our objective is to reveal pretreatment factors which have impact on the biochemical freedom from failure (bFFF) in patients with permanent interstitial seed implants as monotherapy. Methods: Between January 2004 and July 2009, 414 consecutive prostate cancer patients with low or intermediate risk in criteria of NCCN guideline underwent PPB at single institution. All of the pre-treatment pathological diagnoses were made by a central pathologist. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed for pathological/clinical features and bFFF. The Kaplan-Meier method was used to calculate rates of bFFF with the log rank test. Results: The median follow-up length was 36.0 months (range, 1.0-68.6 months). The 2 and 3-year bFFF rates were 98.3% and 96.0%, respectively, for the entire cohort. Pretreatment Gleason score (p<0.0001) had strong impact on bFFF while risk group (p=0.0534) and clinical stage (p=0.563) did not. Especially, patients with GS 4+3 showed lower bFFF than patients with GS 3+4 (p=0.0267 ). Conclusions: Although clinical risk classification has contributed to predict biochemical failure rate in patients with PPB, the patients with Gleason sum score 7 should be divided to group 3+4 and group 4+3 since the clinical outcome may be different between these groups. Therefore, an indication of PPB for patients with Gleason 4+3 may be controversial. No significant financial relationships to disclose.

659 PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUS ESTRAMUSTINE FOR HIGH RISK PROSTATE CANCER FOLLOWED BY RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2010659 PHASE 2 TRIAL OF NEOADJUVANT LHRH PLUS ESTRAMUSTINE FOR HIGH RISK PROSTATE CANCER FOLLOWED BY RADICAL PROSTATECTOMY Takuya Koie, Teppei Okamoto, Kengo Imanishi, Naoki Sugiyama, Yuichiro Suzuki, Kazuyuki Mori, Shigemasa Kudoh, Takahiro Yoneyama, Yasuhiro Hashimoto, Noritaka Kamimura, and Chikara Ohyama Takuya KoieTakuya Koie More articles by this author , Teppei OkamotoTeppei Okamoto More articles by this author , Kengo ImanishiKengo Imanishi More articles by this author , Naoki SugiyamaNaoki Sugiyama More articles by this author , Yuichiro SuzukiYuichiro Suzuki More articles by this author , Kazuyuki MoriKazuyuki Mori More articles by this author , Shigemasa KudohShigemasa Kudoh More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Noritaka KamimuraNoritaka Kamimura More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1046AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Effective treatment for high risk prostate cancer (PC) has not yet been established. We examined efficacy and safety of neo-adjuvant therapy with LHRH agonist + estramustine (EMP) (LHRH+EMP) followed by retropubic radical prostatectomy (RRP). METHODS Risk stratification was performed according to the D□fAmico□fs method. Eighty seven patients with high risk PC were enrolled onto this trial from September 2005 and August 2009. The LHRH + EMP therapy included administration of LHRH and 280 mg/day EMP for 6 months prior to the RRP. Post-therapy pathological evaluation to no residual disease at RRP (pT0), and PSA-free survival were endpoints of interest. RESULTS The average age of the patients was 67.2 years (range 49 to 78 years), and mean initial PSA level was 22.5 ng/ml (range 4.2 to 95.6 ng/ml). The median Gleason sum score was 8 (range 6 to 9), and clinical stage T2c or greater was 76 patients (87.4%). Eighty-six (98.9%) completed 6 months of LHRH+EMP neo-adjuvant therapy without delay for RP. The pT0 was achieved in 4 patients (4.6%). The negative surgical margin was 73 patients (83.9%). At a mean follow-up period of 22.2 months, the PSA-free survival was 75.1%. The 2-year PSA-free survival was 83.8% with negative surgical margin, and 35.9% with positive surgical margin (P <0.0001) (Figure). CONCLUSIONS Six months of LHRH+EMP neo-adjuvant therapy followed by RP is safe and effective. Although the present study is not randomized, this treatment may improve PSA-free survival in high-risk prostate cancer. A prospective randomized trial is warranted. Hirosaki, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e258 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Koie More articles by this author Teppei Okamoto More articles by this author Kengo Imanishi More articles by this author Naoki Sugiyama More articles by this author Yuichiro Suzuki More articles by this author Kazuyuki Mori More articles by this author Shigemasa Kudoh More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Noritaka Kamimura More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years

Background and purpose The effect of predominating Gleason grade (3 + 4 versus 4 + 3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA ⩽ 10 ng/ml, localised PCa is reported. Materials and methods Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA ⩽ 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS). Results Median follow-up was 5.0 years (range 2.0–10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3 + 4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4 + 3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D 90 ⩾ 140 Gy (50% total), compared with 77.0% below 140 Gy ( p = 0.08). Conclusions Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy.