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Background Multiparametric MRI (mpMRI) became recognised in investigating those with suspected prostate cancer between 2010 and 2012; in the USA, the preventative task force moratorium on PSA screening was a strong catalyst. In a few short years, it has been adopted into daily urological and oncological practice. The pace of clinical uptake, born along by countless papers proclaiming high accuracy in detecting clinically significant prostate cancer, has sparked much debate about the timing of mpMRI within the traditional biopsy-driven clinical pathways. There are strongly held opposing views on using mpMRI as a triage test regarding the need for biopsy and/or guiding the biopsy pattern. Objective To review the evidence base and present a position paper on the role of mpMRI in the diagnosis and management of prostate cancer. Methods A subgroup of experts from the ESUR Prostate MRI Working Group conducted literature review and face to face and electronic exchanges to draw up a position statement. Results This paper considers diagnostic strategies for clinically significant prostate cancer; current national and international guidance; the impact of pre-biopsy mpMRI in detection of clinically significant and clinically insignificant neoplasms; the impact of pre-biopsy mpMRI on biopsy strategies and targeting; the notion of mpMRI within a wider risk evaluation on a patient by patient basis; the problems that beset mpMRI including inter-observer variability. Conclusions The paper concludes with a set of suggestions for using mpMRI to influence who to biopsy and who not to biopsy at diagnosis. Key Points • Adopt mpMRI as the first, and primary, investigation in the workup of men with suspected prostate cancer. • PI-RADS assessment categories 1 and 2 have a high negative predictive value in excluding significant disease, and systematic biopsy may be postponed, especially in men with low-risk of disease following additional risk stratification. • PI-RADS assessment category lesions 4 and 5 should be targeted; PI-RADS assessment category lesion 3 may be biopsied as a target, as part of systematic biopsies or may be observed depending on risk stratification. Electronic supplementary material The online version of this article (10.1007/s00330-019-06166-z) contains supplementary material, which is available to authorized users.

Purpose: To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens. Methods: Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007–2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013–2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models. Results: Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis. Conclusions: 3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

Background Active surveillance (AS) of low-risk prostate cancer (PCa) is an accepted alternative to active treatment. However, the conventional diagnostic trans-rectal ultrasound guided biopsies (TRUS-bx) underestimate PCa aggressiveness in almost half of the cases, when compared with the surgical specimen. Purpose To investigate if additional multi-parametric magnetic resonance imaging (mpMRI) of the prostate and MRI-guided in-bore biopsies (MRGB) at AS inclusion would improve selection of patients for active treatment. Material and Methods All patients enrolled in AS programs at two Danish centers, from October 2014 to January 2016, were offered an mpMRI 8–12 weeks after the initial diagnostic TRUS-bx. Candidates had low-risk disease (PSA 6 or GS 6 (3 + 3) lesions with ≥ 6 mm maximal cancer core length (MCCL). Results A total of 78 patients were included and in 21 patients a total of 22 PIRADS-score 4 or 5 lesions were detected. MRGB pathology revealed that 17 (81%) of these and 22% of the entire AS population harbored significant cancers at AS inclusion. In eight (38%) cases, the GS was upgraded. Also, nine patients (43%) had GS 6 (3 + 3) foci with MCCL ≥ 6 mm. Conclusion In an AS cohort based on TRUS and TRUS-bx diagnostic strategies, supplemental mpMRI and in-bore MRGB were able to efficiently reclassify a substantial number of patients as candidates for immediate active treatment.

Deferred active treatment (DAT) strategies, including active surveillance and active monitoring, are a recognised management option for men with localised low-risk prostate cancer. However, there is uncertainty due to heterogeneity of patient selection criteria, follow-up and monitoring characteristics, reclassification thresholds, and which outcome measures should be prioritised. This protocol describes a study led by the European Association of Urology (EAU) Prostate Cancer Guidelines Panel in conjunction with other guideline organisations and societies to develop consensus statements for all domains of deferred active treatment. The project is divided into 3 sequential phases: (1) Systematic review of studies reporting on DAT in order to summarise and define range of heterogeneity regarding all domains; (2) Two-round Delphi online survey involving a large, international panel of healthcare professionals (HCPs) and patients to initiate consensus; and (3) Consensus group meeting involving representatives from HCP and patient stakeholder groups to finalise the consensus process. The consensus statements are expected to be adopted by clinical practice guidelines in order to standardise and guide practice for clinicians and researchers until better evidence emerges. Patient summary: We describe a project aimed at standardising elements of practice in active surveillance/monitoring for early localised prostate cancer, because currently there is great variation and uncertainty regarding how best to conduct them. This will be achieved through a structured process of agreement (i.e. consensus) amongst a large, international panel of healthcare professionals and patients.

Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients., Notch signalling is involved in prostate cancer progression and therapeutic resistance. Here, the authors show that loss of PTEN in prostate cancer models results in increased Notch1 cleavage and activation through CUX1-mediated transactivation of ADAM17.

Tumorigenesis is a multistep process involving co-operation between several deregulated oncoproteins. In this study, we unravel previously unrecognized interactions and crosstalk between Pim kinases and the Notch signaling pathway, with implications for both breast and prostate cancer. We identify Notch1 and Notch3, but not Notch2, as novel Pim substrates and demonstrate that for Notch1, the serine residue 2152 is phosphorylated by all three Pim family kinases. This target site is located in the second nuclear localization sequence (NLS) of the Notch1 intracellular domain (N1ICD), and is shown to be important for both nuclear localization and transcriptional activity of N1ICD. Phosphorylation-dependent stimulation of Notch1 signaling promotes migration of prostate cancer cells, balances glucose metabolism in breast cancer cells, and supports in vivo growth of both types of cancer cells on chick embryo chorioallantoic membranes. Furthermore, Pim-induced growth of orthotopic prostate xenografts in mice is associated with enhanced nuclear Notch1 activity. Finally, simultaneous inhibition of Pim and Notch abrogates the cellular responses more efficiently than individual treatments, opening up new vistas for combinatorial cancer therapy.

// Karine Lefort 1 , Paola Ostano 2 , Maurizia Mello-Grand 2 , Valerie Calpini 1 , Maria Scatolini 3 , Antonella Farsetti 4, 5 , Gian Paolo Dotto 1, 6 , Giovanna Chiorino 2 1 Department of Biochemistry, University of Lausanne, Lausanne, Switzerland 2 Laboratory of Cancer Genomics, Fondazione “Edo ed Elvo Tempia Valenta”, Biella, Italy 3 Laboratory of Molecular Oncology, Fondazione “Edo ed Elvo Tempia Valenta”, Biella, Italy 4 Institute of Cell Biology and Neurobiology, National Research Council, Rome, Italy 5 Internal Medicine Clinic III, Goethe University, Frankfurt am Main, Germany 6 Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA Correspondence to: Giovanna Chiorino, email: giovanna.chiorino@fondazionetempia.org Karine Lefort, email: karine.lefort@unil.ch Keywords: Notch, prostate cancer Received: January 15, 2016 Accepted: June 12, 2016 Published: June 30, 2016 ABSTRACT Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21 WAF1/CIP1 ; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer.

Background The French West-Indies rank first for both prostate cancer incidence and mortality rates. Analyzing diagnostic and therapeutic procedures among patients with prostate cancer, using data from a population-based cancer registry, is essential for cancer surveillance and research strategies. Methods This retrospective observational cohort study was based on data from the Martinique Cancer Registry. Records of 452 patients diagnosed with prostate cancer in 2013 were retrieved from the registry. Data extracted were: socio-demographic and clinical characteristics, circumstances of diagnosis, PSA level at diagnosis, Gleason score and risk of disease progression. Stage at diagnosis and patterns of care among prostate cancer patients were analyzed. Results Mean age at diagnosis was 67 ± 8 years; 103 (28.5%) were symptomatic at diagnosis. Digital rectal exam was performed in 406 (93.8%). Clinical stage was available in 385 (85.2%); tumours were localized in 322/385 (83.6%). Overall, 17.9% were at low risk, 36.4% at intermediate and 31.9% at high risk; 13.8% were regional/metastatic cancers. Median PSA level at diagnosis was 8.16 ng/mL (range 1.4–5000 ng/mL). A total of 373 patients (82.5%) received at least one treatment, while 79 (17.5%) had active surveillance or watchful waiting. Among patients treated with more than one therapeutic strategy, the most frequent combination was external radiotherapy with androgen deprivation (n = 102, 22.6%). Conclusions This study provides detailed data regarding the quality of diagnosis and management of patients with prostate cancer in Martinique. Providing data on prostate cancer is essential for the development of high-priority public health measures for the Caribbean.

PURPOSE: To date no guidelines are available for contouring prostate cancer inside the gland, as visible on multiparametric (mp-) MRI. We assessed inter-institutional differences in interpretation of mp-MRI in the multicenter phase III FLAME trial. METHODS: We analyzed clinical delineations on mp-MRI and clinical characteristics from 260 patients across three institutes. We performed a logistic regression analysis to examine each institute's weighting of T2w, ADC and Ktrans intensity maps in the delineation of the cancer. As reviewing of all delineations by an expert panel is not feasible, we made a selection based on discrepancies between a published tumor probability (TP) model and each institute's clinical delineations using Areas Under the ROC Curve (AUC) analysis. RESULTS: Regression coefficients for the three institutes were -0.07, -0.27 and -0.11 for T2w, -1.96, -0.53 and -0.65 for ADC and 0.15, 0.20 and 0.62 for Ktrans, with significant differences between institutes for ADC and Ktrans. AUC analysis showed median AUC values of 0.92, 0.80 and 0.79. Five patients with lowest AUC values were reviewed by a uroradiologist. CONCLUSION: Regression coefficients revealed considerably different interpretations of mp-MRI in tumor contouring between institutes and demonstrated the need for contouring guidelines. Based on AUC values outlying delineations could efficiently be identified for review. ispartof: RADIOTHERAPY AND ONCOLOGY vol:128 issue:2 pages:321-326 ispartof: location:Ireland status: published

Background: When managing patients with cancer, lymphedema of the lower limbs (LLL) is commonly reported as secondary to the surgical excision and/or irradiation of lymph nodes (LNs). In the framework of lymphoscintigraphic imaging performed to evaluate secondary LLL, some lympho-nodal presentations have been observed that could not be explained by the applied treatments, suggesting that these LLL might be primary. Therefore, all our lymphoscintigraphic examinations that were performed in patients for LLL after surgery for gynecological or urological cancer were retrospectively analyzed in order to evaluate the frequency in which these LLL might not be secondary (either completely or partially) but primary in origin. Methods: Lymphoscintigraphies performed in 33 patients who underwent LN dissection (limited to the intra-abdominal LN) with or without radiotherapy for histologically confirmed ovarian cancer (n = 6), uterine cancer (n = 14 with cervical cancer and n = 7 with endometrial cancer), or prostate cancer (n = 6) were compared to lymphoscintigraphies obtained in primary LLL. Results: In 12 (33% of the) patients (3 men plus 9 women, 4 with cervical cancer and 5 with endometrial cancer), scintigraphy of the lower limbs revealed lympho-nodal presentation that did not match with the expected consequences of the surgical and/or radiological treatments and were either suggestive or typical of primary lymphedema. Conclusions: This retrospective analysis of a limited but well-defined series of patients suggests that the appearance of LLL might not be related to cancer treatment(s) but that these LLL may represent the development of a primary lymphatic disease latent prior to the therapeutic interventions., SCOPUS: ar.j, info:eu-repo/semantics/published

Contains fulltext : 215808.pdf (Publisher’s version ) (Open Access) PURPOSE: Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS: A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS: Functional imaging techniques like (68)Ga PSMA. (68)Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS: Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

Background Pre-treatment magnetic resonance imaging (MRI) can give patient-specific evaluation of 25 suspected pathologically-involved volumes in the seminal vesicles (SV) in prostate cancer patients. By 26 targeting this suspicious volume we hypothesize that radiotherapy is more efficient without introducing more 27 toxicity. In this study we evaluate the concept of using MRI-defined target volumes in terms of tumor 28 control probability (TCP) and rectal normal tissue complication probability (NTCP). Materials and methods Twenty-one high-risk prostate cancer patients were included. Pre-treatment CT 30 images, T2 weighted (T2w) MRI and two multi-parametric MRI were acquired. Overlap between a 31 suspicious volume in the SV observed on T2w images and a suspicious volume observed on either multi-32 parametric MRI was assumed to reflect a true malignant region (named “MRI positive”). In addition the 33 entire SV on the CT-scan was delineated. Three treatment plans of 2Gyx39 fractions were generated per 34 patient: one covering the MRI positive volume in SV and prostate with margin of 11 mm to the MRI positive 35 in the SV and two plans covering prostate and SV using 11mm and 7mm SV margin, respectively. All plans 36 prescribed the same PTV mean dose. Rectal NTCP grade≥2 was evaluated with the Lyman-Kutcher-Burman 37 model and TCP was estimated by a logistic model using the combined MRI positive volume in SV and 38 prostate as region-of-interest. Results 14/21 patients were classified as MRI positive, 6 of which had suspicious volumes in all three MRI 40 modalities. On average TCP for the plan covering prostate and the MRI positive volume was 3% higher (up 41 to 11%) than the two other plans which was statistically significant. The increased TCP was obtained without 42 increasing rectal NTCP grade≥2. Conclusion Using functional MRI for individualized target delineation in the seminal vesicles may improve 44 the treatment outcome in radiotherapy of prostate cancer without increasing the rectal toxicity.

Background: Data regarding the natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) and adjuvant radiotherapy (aRT) are limited. Objective: To evaluate cancer-specific (CSM) and other-cause mortality (OCM) in prostate cancer patients with BCR after RP and aRT. Design, setting, and participants: We identified 336 patients with BCR treated between 1990 and 2006 at two tertiary care centers. Intervention: All patients underwent RP plus aRT. Outcome measurements and statistical analysis: Cox regression analyses were used to evaluate the association between clinicopathologic variables and CSM. The coefficients of CSM-independent predictors were used to develop a novel nomogram. Patients were stratified into groups according to nomogram-calculated CSM probability and median age. Competing-risks survival analyses were used to estimate CSM and OCM for each group. Results and limitations: Ten-year CSM and OCM were 21.5 and 21.7%, respectively. On multivariable analyses, short time to BCR, pathologic Gleason score >= 8, and positive lymph node count of more than two at RP were significantly associated with increased CSM rate (all p 10-30% versus >30%. On competing-risks analysis, 10-yr CSM rate for these groups was 6%, 15%, and 42%, respectively, for patients aged 68 yr. Likewise, 10-yr OCM rate was 24%, 9%, and 10%, respectively, for patients aged 68 yr. The study is limited by its retrospective design. Conclusions: Short time to BCR, pathologic Gleason score >= 8, and more than two positive lymph nodes were independent predictors of CSM in patients with BCR after RP and aRT. Men with these features may benefit from additional secondary therapies, ideally, in a clinical trial setting. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Background We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. Methods For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3.6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. Findings Between May 22,1987, and Oct 31,1995,415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9.1 years (IQR 5.1-12.6). 10-year clinical disease-free survival was 22.7% (95% CI 16.3-29.7) in the radiotherapy-alone group and 47.7% (39.0-56.0) in the combined treatment group (hazard ratio [HR] 0.42,95% CI 0.33-0.55, p

Background: The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. Objective: The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. Design, setting, and participants: We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). Outcome measurements and statistical analysis: Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. Results and limitations: The average number of RLNs was 20.8 (median: 19; interquartile range: 14–25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p = 0.02). Other predictors of CSM were Gleason score 8–10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p 0.006). The study is limited by its retrospective nature. Conclusions: In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. Patient summary: We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

PURPOSE: To understand the reasons for differences in the delineation of target volumes between physicians. MATERIAL AND METHODS: 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. RESULTS: Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. CONCLUSION: These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins).

When prostate needle biopsies are involved discontinuously by tumor, no consensus remains on the optimal method of tumor quantification. We investigated whether discontinuous biopsy involvement usually results from a large tumor focus or multiple small foci. Prostate needle biopsies with discontinuous tumor and corresponding whole-mounted radical prostatectomies from 2008 to 2013 were analyzed. Linear length and percentage of biopsy involvement were measured both including and subtracting the benign intervening tissue. The corresponding region of the prostatectomy specimen was evaluated for tumor size and multifocality. From over 800 biopsy sets and 400 prostatectomies performed annually, 40 patients met inclusion criteria. Excluding benign tissue, length and percentage of biopsy involvement ranged from 1 to 7 mm and 5% to 66% (median 2.5 mm, 20%), whereas including intervening tissue yielded 4 to 15.5 mm and 25% to 100%, (median 7 mm, 70%), respectively. Benign intervening tissue measured from 2 to 10.5 mm (median 3.5 mm). In 31 patients (78%), a single tumor focus was present in the corresponding region of the prostate (the dominant tumor in 25/31). In 9 patients, multiple small foci were present. Eleven patients could have been excluded from active surveillance eligibility by measuring tumor from end to end (>50% involvement), of whom only 1 met criteria for clinically insignificant cancer at prostatectomy. Discontinuous tumor in a prostate biopsy often results from a single tumor focus in the corresponding region of the prostate (78%). Therefore, we recommend that an end-to-end measurement be provided, with accompanying diagnostic comment that this often correlates with the size of a single tumor focus.

Background: According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes. Objective: To develop and internally validate novel nomograms predicting cancerspecific mortality (CSM)-free rate in pN1 patients. Design, setting, and participants: We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010. Outcome measurements and statistical analysis: Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated. Results and limitations: All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p

Silva, Fernando Calais da Silva, Fernando Manuel Calais da Goncalves, Frederico Santos, Americo Kliment, Jan Whelan, Peter Oliver, Tim Antoniou, Nicos Pastidis, Spiro Marques Queimadelos, Anton Robertson, Chris ENG 2013/04/16 06:00 Eur Urol. 2013 Apr 4. pii: S0302-2838(13)00342-4. doi: 10.1016/j.eururo.2013.03.055.; International audience; BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25mg) analogue plus CPA 200mg/d. Patients whose prostate-specific antigen (PSA) was /=20 ng/ml or they were symptomatic) or the continuous arm (CPA 200mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA /=2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Background: The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial. Objective: We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features. Design, setting, and participants: We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes. Outcome measurements and statistical analysis: Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors. Results and limitations: On multivariable analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p = 0.4). Conversely, in patients with a risk score >= 2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study. Conclusions: ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The translationally controlled tumor protein (TCTP) is an abundantly expressed protein found in a wide range of organisms from both the animal and plant kingdom. Initially described as a growth-related protein, knowledge of the biological actions of TCTP has been recently extended to include calcium binding, regulation of apoptosis, and microtubules stabilization. This report describes expression, distribution, and characterization of TCTP in human prostatic tissues and cell lines.Samples were analyzed by Western blot, RT-PCR, immunohistochemistry, and confocal microscopy. Calcium binding activity of the recombinant human prostatic protein was evaluated on a calcium overlay assay. A public SAGE database was analyzed to determine TCTP expression levels in normal and cancer tissues.TCTP protein and mRNA were detected in all the specimens and cell lines analyzed. The protein was mainly expressed by the secretory luminal epithelial and basal layer cells. A significant amount of protein was present in the prostatic fluids. Subcellular distribution studies in prostate epithelial cells detected the protein in the cytoplasm in interphase and colocalized with tubulin during mitosis. The calcium binding capacity of prostatic TCTP was shown in vitro. Finally, SAGE data indicated TCTP as the calcium binding protein with the highest expression levels among those examined.The results of the present study demonstrate, for the first time, the expression of TCTP in the human prostate and in prostate cancer cells, and suggest the involvement of the protein in key-processes such as apoptosis, cellular differentiation, and in the control of sperm functions.