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Introduction: Incisional and parastomal hernias are frequent complications after cystectomy. The aim of our study was to define their incidence, identify risk factors related to the patient and the surgical technique, and identify means of prevention., Material: This was a multicenter, retrospective study, analyzing clinical and radiological data from 521 patients operated on for cystectomy between January 2010 and December 2020., Results: In total, 521 patients, 471 men and 50 women, mean age 68.8years, were included. Thirty-one patients (6.6%) presented with an evisceration. Risk factors were a history of evisceration (OR: 14.1; 95% CI: [3-66]; P=0.0008), COPD (OR: 3.5; 95% CI: [1.3-9 .4]; P=0.0119), ischemic heart disease (OR: 4; 95% CI: [1. 6-10]; P=0.0036), and split-stitch closure (OR: 3.1; 95% CI: [1.065-8.9]; P=0.0493). Fifty-one patients (9.9%) presented with an incisional hernia. Risk factors were a history of COPD (OR: 4, 95% CI: [2.1-7.6]; P<0.001) and postoperative pulmonary infection (OR: 5.3; 95% CI: [1.05-26.4]; P=0.0079). Seventy-nine patients (15.28%) had a parastomal hernia. Overweight was a risk factor (OR: 2.3; 95% CI: [1.3-4.5]; P=0.0073)., Conclusion: Patients who are overweight or have pulmonary comorbidities are at greater risk of developing parietal complications after cystectomy., Level of Evidence: III., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting., Participants: COBLAnCE ( CO hort to study BLA dder C anc E r) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up., Findings to Date: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy., Future Plans: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age., Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr)., Design, Setting, and Participants: We evaluated 25589 men aged 55-59 yr, 16898 men aged 60-64 yr, and 12936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU)., Outcome Measurements and Statistical Analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr., Results and Limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice., Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening., Patient Summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Prostate cancer is a frequent disease and one of the main treatments used is androgen deprivation therapy, which is a therapy with disabling side effects. Non-pharmacological interventions (NPIs) are evidenced based, non-invasive interventions on human health. They are classified into five categories (physical, psychological, nutritional, digital, elemental). The NPIs sphere is booming and still remains underused in this context., Methods: A systematic review concerning randomized controlled trials was executed according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the "Medline" and "Kalya Research" databases. After searching and selecting eligible publications, we included 37 randomized controlled trials., Results: The majority of articles concerned physical NPIs with 30 clinical studies, 3 publications dealt with nutritional NPIs, 2 with psychological NPIs and 2 articles concerned elemental NPIs. No publication about digital NPI was found. All of the studies aimed to manage and improve the side effects of treatment. No elemental NPI has demonstrated benefit. Only one psychological NPI and one nutritional NPI were effective. Five types of physical NPI protocols have shown efficacy. The main benefits related to physical abilities, body composition, osteoporosis, quality of life, fatigue, reduced cardiovascular risk and finally anxiety and depression., Conclusion: Non-pharmacological interventions, especially physical ones, are effective in managing and reducing the side effects associated with androgen deprivation therapy and should be offered to patients in this context., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Sleep disturbances have been singled out for their implication in the risk of several cancer sites. However, results for prostate cancer are still inconsistent., Methods: We used data from the EPICAP study, a French population-based case-control study including 819 incident prostate cancer cases and 879 controls frequency matched by age. Detailed information on sleep duration on work/free days, and sleep medication over lifetime was collected., Results: Sleep duration and sleep deprivation were not associated with prostate cancer, whatever the aggressiveness of prostate cancer. However, sleep deprivation was associated with an increased prostate cancer risk among men with an evening chronotype [OR, 1.96; 95% confidence interval (CI), 1.04-3.70]. We also observed an increased risk of prostate cancer with higher duration of sleep medication use (Ptrend = 0.008). This association with long duration of sleep medication use (≥10 years) was more pronounced among men who worked at night 15 years or more (OR, 3.84; 95% CI, 1.30-11.4) and among nonusers of NSAID (OR, 2.08; 95% CI, 1.15-3.75)., Conclusions: Our results suggested that chronotype, night work, or NSAID use could modify the association between sleep disorders and prostate cancer occurrence needing further investigations to go further., Impact: EPICAP is the first study, which investigates several sleep indicators taking into account potential effect modifiers. If our findings were confirmed, we could identify subgroups of men at higher risk of prostate cancer that may be accessible to preventive measures., (©2022 American Association for Cancer Research.)

Objective: To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology., Patients and Methods: A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre., Results: Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists., Conclusion: In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected., (© 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Ltd.)

Background: Although prostate cancer (PCa) is the most frequent male cancer in industrialized countries, little is known about its aetiology. The literature has suggested an influence of the environment, including occupational exposures, but results are inconsistent. In this context, we investigated PCa risk associated to employment among several occupations using data from EPICAP study., Methods: EPICAP is a French population-based case-control study including 819 PCa incident cases and 879 controls frequency-matched on age. In-person interviews gathered data on potential risk factors and lifetime occupational histories for each job held at least 6 months. Then, occupations were coded using ISCO 68. Unconditional logistic regressions were performed to assess the association between occupations (ever occupied and by duration) and PCa risk, whether all and aggressive, after adjusting for potential confounders., Results: For ≥10 years of employment, we found positive associations with PCa, whether overall and aggressive, among Medical, Dental and Veterinary workers (OR (odds ratios) =5.01 [95% confidence interval] [1.27; 19.77]), Members of the armed forces (OR = 5.14 [0.99; 26.71]) and Fishermen, hunters and related workers (OR = 4.58 [1.33; 15.78]); whether overall and non-aggressive PCa, among Legislative officials and Government administrators (OR = 3.30 [1.10; 9.84]) or Managers (OR = 1.68 [1.18; 2.41]); however a negative association, whether overall and non-aggressive PCa, among Material-Handling and Related Equipment Operators, Dockers and Freight Handlers (OR = 0.40 [0.17; 0.97])., Conclusion: Excess PCa risks were observed in the EPICAP study mostly among white collar workers exposed to several factors in their work environment. These emerging associations can be used to lead future research investigating specific occupational exposures., (© 2022. The Author(s).)

Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials., Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC)., Design Setting and Participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up., Outcome Measurements and Statistical Analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results., Results and Limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results., Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms., Patient Summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified., (© 2021 The Author(s).)

Aim: The objective of this study is to present the history of cancers of the external genital organs of male in Hérault using data from the Hérault tumor register (RTH) over a period of 30 years., Patients and Methods: Using the RTH database, we studied the development of testicular germ cell tumors (TGCT) and penile cancer (PC) over 30 years, from 1987 to 2016. We analyzed the incidence and mortality data for these tumors. We compared these results to French, European and global data., Results: In 30 years of registration we have recorded 725 cases of TGCT and 175 cases of PC. The age standardized incidence rate (ASR) of TGCT has doubled between 1987 and 2016 (4.2 per 100,000 in 1987 and 9.3 per 100,000 in 2016). It was multiplied by 2.63 in the population of patients aged 30 to 44. There is a decrease of the mortality rate with a ASR of 0.8 deaths per 100,000 in 1987, and 0.4/100 000 in 2016. The PC incidence ASR was stable between 1987 and 2016 (0.4-0.9/100,000). Mortality is stable with a ASR between 0.1 and 0.3 deaths per 100,000 between 1987 and 2016., Conclusion: The incidence of TGCT has increased sharply in the Hérault over the past 30 years, while a decrease in mortality has been observed. The proportion of seminomas is increasing; it has gone from 53 % to 60 % in 30 years in the Hérault. The incidence and mortality of PC shows a stability in the Hérault over the past 30 years., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices., Competing Interests: Conflicts of interest The development of these guidelines was wholly funded by SFMPP. The panelists received no payments. The complete CoI for researchers who contributed to the guidelines are provided in supplementary data. Categories for disclosure of CoI include employment; leadership; stock or other ownership; honoraria, consulting or advisory role; speaker’s bureau; research funding; patents, royalties, other intellectual property; expert testimony; travel, accommodations, expenses; and other relationships., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is a lack of information about the burden of metastatic castration-resistant prostate cancer (mCRPC). The present work aims to estimate the incidence and prevalence of mCRPC in 2014 using the French nationwide healthcare database (SNDS)., Methods: Prevalence and incidence were estimated based on an SNDS extraction of men covered by the general healthcare insurance (86 % of the French population), and aged ≥40. Patients with mCRPC were identified amongst prostate cancer cases using an algorithm estimating a date of first metastasis management and a date of castration resistance. This algorithm was validated by clinical experts through a blind review of 200 anonymized medical charts from SNDS data. Prevalence and incidence were standardized on the European Standard Population (2013 edition)., Results: Prevalence and incidence of mCRPC were estimated as, respectively, 62 and 21 cases per 100 000 men in 2014. Less than one mCRPC case per 100 000 was observed in men aged 40-49. Maximum mCRPC incidence was in men aged 80-89 (175 per 100 000). The algorithm used for mCRPC identification had 97 % positive and 99 % negative predictive values., Conclusion: The good performances of the algorithm for mCRPC identification and the consistency of the generated results with the existing data highlight the robustness of these first estimates of mCRPC prevalence and incidence. Future updates will call for algorithm adjustment as practices evolve over time. These first real-life data will serve for future follow-up of the impact of changes in the management of prostate cancer., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: In 2016, the Herault tumor registry collected 1961cancers in urology (21.4 % from all Herault cancers this year). RHESOU was created to complete RTH' data with specific parameters in onco-urology. The aim of this study is to describe RHESOU and to give some examples with our first results., Material and Methods: In November 2018, RHESOU (Registry HErault Specialised in Onco-Urology) was founded with the same registry recommendations. It collects specific oncologic parameters and also complete RTH's data. For each urological cancer, a specific survey with different choices was performed to collect a maximum of data which could be present in patients' file. These surveys were used for urological cancers cases that live in Herault in 2017., Results: In 2017, we collected 970 prostate cancers, 581 bladder cancers, 212 kidney cancers, 51 upper excretory tract cancers, 28 testicle cancers and 9 penil cancers. Our urological data collection gives many possibilities to create many requests for detailed analysis in urological cancers. In this article, we reported data from kidney, bladder and prostate cancers., Conclusions: RHESOU is a new tool opened to the different urologic corporations (urologists, pathologists, oncologists, radiotherapists, radiologists) that permits an overview in urological cancers in Herault. Finally, one important aim is that this tool will be adapted when new treatments or new important parameters appear in the years ahead., Level of Evidence: 3., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: - The purpose of the guidelines national committee ccAFU was to propose updated french guidelines for prostate cancer., Methods: - A Medline search was achieved between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of prostate cancer (PCA), and to evaluate the different references specifying their levels of evidence., Results: - The guidelines outline the genetics, epidemiology and diagnosis of prostate cancer, as well as the concepts of screening and early detection. MRI, the gold standard imaging test for localized cancer, is indicated before prostate biopsies are performed. The therapeutic methods are detailed and indicated according to the clinical situation. Active surveillance is a reference therapeutic option for low-risk tumours with a low evolutionary risk. Early salvage radiotherapy is indicated in case of biological recurrence after radical prostatectomy. Androgen deprivation therapy (ADT) remains the backbone therapy in the metastatic stage. Docetaxel in combination with ADT improves overall first-line survival in synchronous metastatic prostate cancer. In this situation, the combination of ADT with abiraterone is also a standard of care regardless of tumor volume. Recent data indicate that ADT should be indicated with a new generation of hormone therapy (Apalutamide or Enzalutamide) in metastatic synchronous or metachronous patients, regardless of tumour volume. Local treatment of prostate cancer with radiotherapy improves survival in synchronous oligometastatic patients. Targeted treatment of metastases is being evaluated. In patients with castration-resistant prostate cancer (CRPC), new therapies that have emerged in recent years help to better control tumor progression and improve survival., Conclusion: - These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: Prostatectomy (PT) is a common procedure performed by many urologists. In 2018, 20,207 prostatectomies were performed in France, and few studies evaluated the perioperative habits of urologists. As part of writing guidelines for enhanced recovery after surgery (ERAS) we wished to evaluate practice of urologists in their hospital management of a prostatectomy., Materiel and Methods: A questionnaire was sent by Survey Monkey in June and July 2018 to all urologists who are members of the French Association of Urology., Results: One hundred and sixty seven urologists (14%) answered the questionnaire, 62% have private practice. The average number of operators per center performing PT was 4, with a median number of 70 interventions (0 to 486) per center in 2018. Open surgery is still gold standard (39.13%), followed by the robot-assisted transperitoneal laparoscopic (34.78%) and standard laparoscopic (24.22%). Alimentation, like first stand-up, was re-established on the first post-operative day, and the average hospital stay was 4±2 nights. The removal of the bladder catheter was most often performed at home by nurse (49.06%), one week after surgery. Only 10.06% of urologists systematically perform a cystography before removal urinary catheter., Conclusion: The perioperative management of prostatectomy in France is relatively homogeneous, between urologists. The length of hospital stay remains important and could be reduced by proposing an ERAS protocol as has been obtained for cystectomy., Level of Evidence: III., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: The French population is facing the COVID-19 pandemic and the health system have been reoriented in emergency for the care of patients with coronavirus. The management of cancers of the urinary and male genital tracts must be adapted to this context., Material and Method: An expert opinion documented by a literature review was formulated by the Cancerology Committee of the French Association of Urology (CCAFU)., Results: The medical and surgical management of patients with any cancers of the urinary and male genital tracts must be adapted by modifying the consultation methods, by prioritizing interventions according to the intrinsic prognosis of cancers, taking into account the patient's comorbidities. The protection of urologists from COVID-19 must be considered., Conclusion: The CCAFU issues an expert opinion on the measure to be taken to adapt the management of cancers of the male urinary and genital tract to the context of pandemic by COVID-19., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: European Randomized Study of Screening for Prostate Cancer (ERSPC) mortality results were reported for 7 European countries (excluding France) and showed a significant reduction in Prostate cancer (PCa) mortality. As those results have not been part of the global ERSPC results, it is of interest to report PCa mortality at a median follow-up of 9 years for French section of ERSPC., Material and Methods: Two administrative departments were involved in the study. Only men after randomization in the screening group were invited by mail to be screened by PSA testing with two rounds at 4-6 year intervals. Biopsy was recommended if PSA>=3.0 ng/mL. No information other that the French Association of Urology recommandations on the use of PSA was offered to the control group (own decision of physicians and patients). Follow up was based on cancer registry database. Contamination defined as the receipt of PSA testing in control arm was measured. Poisson regression models were used to estimate the Rate Ratio (RR) of PCa mortality and incidence in the screening vs. control arm., Results: Starting from 2003, 80,696 men aged 55-69 years were included. The percentage of men in the screening arm with at least one PSA test (compliance) was 31%. Compared to the control arm, PCa incidence increased by 10% in the screening arm (RR=1.10; 95% CI=[1.04-1.16], P=0.001), but PCa mortality did not differ (0.222 and 0.215 deaths/1000 person-years; RR=1.03[0.75-1.42], P=0.9)., Discussion: Limitations include low participation rate. PSA testing in the control arm was observed in 32% of men (contamination)., Conclusions: Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up., Level of Evidence: 3., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality., Objective: To determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended., Design, Setting, and Participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55-69yr), selected from population registry., Outcome Measurements and Statistical Analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended., Results and Limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently., Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level., Patient Summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer., (Copyright © 2019. Published by Elsevier B.V.)

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients' representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the "actionability" of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: DOI:10.1016/j.purol.2019.01.007. C’est cette nouvelle version qui doit être utilisée pour citer l’article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the DOI:10.1016/j.purol.2019.01.007. That newer version of the text should be used when citing the article., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Obesity is associated with an increased risk of several cancers, but inconsistent results have been observed between body mass index (BMI) and prostate cancer (PCa) risk. However, some associations have been reported with other indicators such as waist circumference (WC) and waist-hip ratio (WHR). We investigated the role of anthropometric indicators in PCa risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). EPICAP is a population-based case-control study that included 819 incident PCa in 2012-2013 and 879 controls frequency matched by age. Anthropometric indicators (weight, height, WC, and hip circumference) have been measured at interview. Logistic regression models were used to assess odds ratios (ORs) for the associations between anthropometric indicators (BMI, WC and WHR) and PCa risk. We observed a slight, but not significant increased risk of PCa for men with a WC > 94 cm (OR 1.20, 95% CI 0.92-1.56) and for men with a WHR ≥ 0.95 (OR 1.30, 95% CI 1.00-1.70 between 0.95 and 1.00, OR 1.25, 95% CI 0.96-1.61 above 1.00). Associations were more pronounced after adjustment and stratification for BMI and in men with aggressive PCa. Our results suggest that abdominal obesity may be associated with an increased risk of PCa, especially aggressive PCa., Competing Interests: CONFLICTS OF INTEREST Nothing to declare.

Epidemiological studies have suggested that prostatitis may increase the risk of prostate cancer due to chronic inflammation. We studied the association between several genitourinary infections and the risk of prostate cancer based on data from the EPICAP study. EPICAP is a population-based case-control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls have been face to face interviewed using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer, and personal history of genitourinary infections: prostatitis, urethritis, orchi-epididymitis, and acute pyelonephritis. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Overall, 139 (18%) cases and 98 (12%) controls reported having at least one personal history of genitourinary infections (OR = 1.64 [1.23-2.20]). The risk increased with the number of infections (p-trend < 0.05). The association was specifically observed with personal history of chronic prostatitis and acute pyelonephritis (OR = 2.95 [1.26-6.92] and OR = 2.66 [1.29-5.51], respectively) and in men who did not use any non-steroidal anti-inflammatory drugs (OR = 2.00 [1.37-2.91]). Our results reinforce the hypothesis that chronic inflammation, generated by a personal history of genitourinary infections, may play a role in prostate carcinogenesis., (© 2018 UICC.)

Introduction: Familial aggregation is now well established with an increased risk of prostate cancer in patients with a family history of prostate cancer in first degree relatives. The aim of this paper was to investigate the role of family history of cancer in first degree relatives in prostate cancer risk., Results: As expected, a family history of prostate cancer in first-degree relatives was more frequent in cases than in controls (OR 3.10, 95% CI 2.32-4.15). A family history of early BCa (before age 50) in first-degree relatives was more frequent in cases than in controls (OR 1.79, 95% CI 1.09-2.94) with higher risk of aggressive PCa. The association was more pronounced for BCa in daughters (OR 15.26 95% CI 1.95-120)., Conclusions: In summary, a family history of BCa in first degree relatives before age 50 may increases the risk of PCa with higher Gleason score. This finding could suggest a specific prostate surveillance and/or genetic counselling for men who present such familial history., Methods: EPIdemiological study of Prostate CAncer (EPICAP) is a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. Detailed information on family history of cancer in first degree relatives (parents, brothers and sisters, children) was collected as well as the age of occurrence and the localization of each cancer. Overall, 819 cases and 879 controls have been included., Competing Interests: CONFLICTS OF INTEREST None.

Purpose: Postoperative serum C-reactive protein (CRP) can be measured after major abdominal surgery to predict of complications at postoperative day (POD) 4. However, in urology, no studies have been conduced to analyze the role of CRP after radical cystectomy. The present study aims to analyze the relationship between a high postoperative level of CRP and the presence of complications after radical cystectomy for cancer., Materials and Methods: This multicenter retrospective study included 313 patients treated with radical cystectomy for cancer between January 2013 and July 2016. Among the patients, 57.5% of patients received urinary diversion using a Bricker ileal conduit, 30.5% an orthotropic ileal neobladder, and 11.5% had an ureterocutaneostomy., Results: Three hundred and thirteen patients were included (mean age 68.1±9.2 years). Among the patients, 26.5% had grade≥2 complications, according to the Clavien-Dindo classification. In multivariate analysis, only CRP level at POD 4 predicted the risk of a complication (P<0.001). CRP>150mg/L at POD 4 was strongly associated with a risk of a postoperative complication after a cystectomy (OR=81.42, 95% CI [25.6-258.3], P<0.001). CRP assessed on POD4 was reliable at ruling out the existence of an infectious complications with a negative predictive value of 0.94. The main limitation of our study was it observational design., Conclusions: CRP at POD4 with a threshold of 150mg/L would reliably predict the risk of postoperative complications after cystectomy. Monitoring postoperative CRP could help adapt rehabilitation protocols after radical cystectomy and also the early management of complications., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population-based case-control study carried out in 2012-2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All-NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61-0.98, especially in men using NSAIDs that preferentially inhibit COX-2 activity (OR 0.48, 95% CI 0.28-0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53-0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27-0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07-0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti-COX-2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo ® ) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Data from the literature support with strong evidence the addition of docetaxel to androgen-deprivation therapy (ADT) for men with metastatic prostate cancer, and starting therapy for the first time. A meta-analysis of three randomized controlled trials showed a significant improvement of overall survival when ADT was combined with docetaxel when compared to ADT alone (HR=0.77; 95% CI: 0.68-0.87; p<0.0001). Consequently, combination therapy should be considered presently as the new standard of care, using 6 cycles of docetaxel, without prednisone. However, candidates for this upfront combination therapy in whom the balance between its side effects and benefits is favorable are still to be identified more precisely. Patients' stratification according to Gleason score, previous local treatment and age or performance status were shown to have a prognostic impact. The volume of metastases, as defined in the CHAARTED study for instance, could be an interesting predictive factor. However, data accumulated until now remain only hypothesis generating and further analysis and studies are needed to establish any potential discriminating factors. Several new efficient therapeutic options are now available in prostate cancer management and should be evaluated against a chemo-hormonal combination therapy. Other trials are warranted to establish the role of docetaxel in earlier stages of the disease, the combination with the new hormonal therapies as well as the best management options after docetaxel., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure., Materials and Methods: Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure., Results: The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term., Conclusion: Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The purpose of the guidelines national committee CCAFU was to propose updated french guidelines for localized and metastatic prostate cancer (PCa)., Methods: A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of PCa, to evaluate different references with levels of evidence., Results: Epidemiology, classification, staging systems, diagnostic evaluation are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of > 74Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival., Conclusions: These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer. © 2016 Elsevier Masson SAS. All rights reserved., (© 2016 Elsevier Masson SAS. Tous droits réservés.)

Introduction: An increasing number of patients with prostate cancer (PC) are diagnosed and treated. The aim of this study was to investigate urinary incontinence (UI) and sexual dysfunction (SD) two years after treatment for localized prostate cancer (PC)., Methods: This study followed all cases of localized PC diagnosed between 2008 and 2009 in men aged≤65years old and still alive two years after treatment. In total, 437 men were recruited. Data were collected using a standardized questionnaire and by cross-checking with data from the cancer registry. Descriptive and comparative analyses were performed to evaluate persisting UI and SD at 2years., Results: At two years after treatment, UI was persistent in 48.8%; 41.2% had used urinary protections, and 39.2% had used at least 1 pad/day; 55.2% reported financial difficulties for purchasing protective pads. In total, 22.7% did not consult a specialist for UI. SD was persistent in 82.8%; 30.4% did not consult a specialist for SD. SD had a negative impact on the sex life of patients and their partners. After adjustment for cancer stage, prostatectomy was significantly associated with persisting UI and SD at two years., Conclusion: Two years after treatment, rates of persisting UI and/or SD remain high. Treatment by prostatectomy was significantly associated with an increased risk of persisting adverse effects at two years. The different toxicities between treatments should be presented to patients before initiating therapy in order to encourage the patient to contributed to shared treatment decision-making., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

Introduction: Through a cross-sectional survey, we tried to assess whether practices of urologists and radiation oncologists are uniform when faced with similar clinical situations., Materials and Methods: A self-administered questionnaire was mailed to all French urologists and radiation oncologists. Respondents were asked about their practices through 11 case scenarios. The scenarios cover most of localized prostate cancer situations and were gradually organized depending on prostate cancer progression risk and the age of the patient. The eight first scenarios address the situation of treatment-naive patients, and the last cases were about the management of patients after radical prostatectomy. Physicians were asked to choose a treatment modality for each case. The responses were first stratified according to the intention to treat: either curative-intent treatment or palliative. The curative-treatment modality chosen were afterward assessed. The responses to clinical scenarios were compared between the two specialties., Results: Concerning the intention to treat, practice patterns were overall consistent except in one case. Indeed, a higher rate of radiation oncologists prefer curative-intent treatment for intermediate-risk prostate cancer in aged patients: 57.4 versus 14.6 % (p < 0.001). Each medical specialist prefers the treatment that he himself delivers (p < 0.005). For intermediate-risk prostate cancer in 65-year-old patient: 96.5 % of urologists chose radical prostatectomy versus 37.7 % of radiation oncologists (p < 0.001). Fewer urologists (almost 14 %) compared to radiation oncologists (47.5 %) would prescribe adjuvant treatment after radical prostatectomy for T3a R0 prostate cancer with post-operative PSA undetectable (p < 0.001)., Conclusion: Significant differences were found in therapeutic approach between the two main specialties that deal with localized prostate cancer.

Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality., Design, Setting, and Participants: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis., Outcome Measurements and Statistical Analysis: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis., Results and Limitations: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller., Conclusions: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr., Patient Summary: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: COU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU., Methods: Between December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors., Results: Among the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years., Conclusions: Biochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders' patients could beneficiate from AA for more than 3 years.

Purpose: Prostate biopsy side effects have a role in the controversy over screening for prostate cancer. We measured the precise incidence of infection after prostate biopsy and determined risk factors., Materials and Methods: We performed a prospective, multicenter study in France from April to June 2013. All prostate biopsies done during this period were included in study. A web based questionnaire was used to identify patient characteristics, biopsy methods and postoperative infectious episodes. External audit helped ensure data completeness. The primary outcome was the post-biopsy infection rate. We determined risk factors for infectious complications using univariate and multivariate analysis., Results: The study included 2,718 patients, of whom 6% reported receiving antibiotics in the previous 6 months and 7.4% had a history of prostatitis. Recommended antibiotic prophylaxis consisting of 2 fluoroquinolone tablets 2 hours before examination for prostate biopsy was noted in 78.3% of cases. Post-biopsy sepsis was found in 76 subjects (2.8%). On multivariate analysis predictors of post-biopsy sepsis were noncompliance with antibiotic prophylaxis guidelines (OR 2.3, 95% CI 1.4-3.9, p = 0.001), antibiotic treatment in the previous 6 months (OR 2.1, 95% CI 1.1-3.9, p = 0.015) and a history of prostatitis (OR 1.7, 95% CI 1.2-2.4, p = 0.002)., Conclusions: In this study the incidence of post-prostate biopsy sepsis was 2.8% and no deaths were reported. Risk factors identified on multivariate analysis were noncompliance with antibiotic prophylaxis according to guidelines, antibiotic treatment in the previous 6 months and a history of prostatitis., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years., Methods: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736., Findings: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88)., Interpretation: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening., Funding: Each centre had its own funding responsibility., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer., Methods: Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology., Results: The median overall survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level <11.5 ng/mL and 1.3 years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4)., Conclusions: Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer.

Purpose: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT)., Methods: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses., Results: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030)., Conclusions: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting., Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control., Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months., Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To try and identify a molecular signature for pathological staging and/or grading. through microarray analysis., Patients and Methods: We performed a prospective multicentre study between September 2007 and May 2008 that included 108 bladder tumours (45 pTa, 35 pT1 and 28>pT1). Microarray analysis was performed using Agilent Technologies Human Whole Genome 4 × 44K oligonucleotide microarrays (Agilent, Santa Clara, CA, USA). A 'dual colour' method was used vs a reference pool of tumours. From the lists of genes provided by the Biometric Research Branch class comparison analyses, we validated the microarray results of 38 selected differentially expressed genes using reverse transcriptase quantitative PCR in another bladder tumour cohort (n = 95)., Results: The cluster 'superficial vs invasive stage' correctly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high grade superficial tumours, but these differences were less well defined than the difference observed for staging., Conclusions: We confirmed that the histopathological classification into subgroups pTa, pT1a and pT1b can be translated into a molecular signature with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b) stages., (© 2013 The Authors. BJU International © 2013 BJU International.)

Introduction: The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer., Methods: Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation., Results: Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways., Conclusion: From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The analytical and clinical validation of new biomarkers for the early detection of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to calculate a standardized PHI index linked to a higher probability of a positive biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for prostate cancer diagnosis. The purpose of this study is to validate the analytical performance of the (-2)proPSA and to determine the predictive value of PHI for the early detection of prostate cancer. Analytical performances are correct. It is not necessary to dilute samples before analysis. The stability of (-2)proPSA is good until at least 3 hours at room temperature before centrifugation. The study of the PSAT, PSAL, (-2)proPSA and PHI values in a population of patients consulting for an early prostate cancer diagnosis shows that the index PHI is the most powerful predictive marker of cancer with an area under ROC curve of 0.70, whereas it is only 0.56 for total PSA.

Objective: To assess the frequency, circumstances, and possible medico-legal consequences of the pT0 prostate cancer, defined by the absence of tumor in a radical prostatectomy specimen., Methods: Six centers retrospectively identified all cases of pT0 and selectionned those that occurred without prior hormone therapy or prostate resection. Preoperative data, histological report and clinical and biological outcome were analyzed. The lawsuits' registry in pathology were consulted at insurance companies., Results: Thirty cases of pT0 prostate cancer (0.4%) were reported on 7693 patients. The median age was 63years, PSA 7.4ng/mL. The number of positive preoperative biopsies ranged from one to four for a median tumor length of 1mm (0.3 to 18mm). The biopsy Gleason score was 3+3 for 23 patients, less than 5 for six others and included a contingent of grade 4 in two patients. With a median follow-up of 82months, no clinical or biochemical recurrence was observed. One patient complaint for pT0 prostate was found in the insurances registry., Conclusion: The occurrence of a prostate pT0 called into question all the diagnostic procedures and surgical indication. To avoid a forensic procedure, urologists should inform patients of the possibility of this situation before radical prostatectomy., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Despite development and widespread of PSA, current tools evaluating prostate cancer still give inconsistent or insufficiently relevant results. As encouraging data raised from circulating tumor cells detection in colon or breast cancer, they were evaluated as a surrogate prostate cancer biomarker. Tumor cells need to leave their surrounding primary environment and to survive in mesenchymal environment before they spill and metastasize. Basic research revealed several mutations required through a complex transition phenomenon, including dormancy steps. Circulating cells detection techniques are based on molecular and immunologic methods. Most of them need an enrichment step to improve sensibility and/or specificity. As of today, Veridex' CellSearch is the only FDA approved technique in the evaluation of castration resistant prostate cancer response to new drugs. Clinical research using other techniques highlighted the need for clinical endpoints, as there's no relevant tool and as techniques' target differ. Further studies are required to improve circulating tumors cells' staging and prognosis value. Cellular characterization may be the way to identify metastasis development potential more than the spillage burden. Those techniques still need improvements before they are included in daily practice decisional trees.

Background: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up., Methods: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer., Results: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality., Conclusions: Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Background. To assess the feasibility of salvage intensity-modulated radiation Therapy (IMRT) and to examine clinical outcome. Patients and Methods. 57 patients were treated with salvage IMRT to the prostate bed in our center from January, 2007, to February, 2010. The mean prescription dose was 68 Gy in 34 fractions. Forty-four patients received concomitant androgen deprivation. Results. Doses to organs at risk were low without altering target volume coverage. Salvage IMRT was feasible without any grade 3 or 4 acute gastrointestinal or urinary toxicity. With a median follow-up of 21 months, one grade 2 urinary and 1 grade ≥2 rectal late toxicities were reported. Biological relapse-free survival was 96.5% (2.3% (1/44) relapsed with androgen suppression and 7.7% (1/13) without). Conclusion. Salvage IMRT is feasible and results in low acute and chronic side-effects. Longer follow-up is warranted to draw conclusions in terms of oncologic control.

Objective: •To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR)., Patients and Methods: •Patient data were derived from the multicentre-based @-Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm® HIFU. •PSA level was measured at 3-month intervals. Patients were stratified into four PSA nadir groups: group 1, ≤0.2 ng/mL; group 2, 0.21-0.5 ng/mL; group 3, 0.51-1 ng/mL; and group 4, >1 ng/mL. •Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2 ng/mL) and the Phoenix definition (PSA nadir + 2 ng/mL). •Biopsy was performed at 3-6 months post-HIFU or if a PSA level was recorded that was considered clinically relevant., Results: •The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub-groups were as follows: 84, 64, 40 and 30% for groups 1-4, respectively. •The equivalent 5-year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively. •Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub-groups (91.6 vs 73.1%; P < 0.001). •The present study is limited by its retrospective nature and variations in clinical practice across participating centres., Conclusion: •This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To estimate the effect of predictive factors for oncologic outcomes after radical prostatectomy (RP) for high-risk prostate cancer (PCa)., Methods: A total of 813 patients underwent RP for high-risk PCa in a national retrospective multi-institutional study. High-risk PCa was defined as follows: prostate-specific antigen (PSA) level>20 ng/mL, Gleason score 8-10, and/or clinical Stage T2c-T4 disease. The preoperative criteria of high-risk PCa were studied in a logistic regression model to assess the correlations with the pathologic findings in the RP specimens. The predictive factors isolated or combined in scores were assessed by Cox multivariate and Kaplan-Meier analyses in predicting PSA failure (recurrence-free survival [RFS]) and overall survival (OS)., Results: The median follow-up was 64 months. Organ-confined disease was reported in 36.5%. The 5-year RFS, metastasis-free survival, and OS rate was 74.1%, 96.1%, and 98.6%, respectively. Each preoperative criteria of high-risk PCa was an independent predictor of PSA failure. The PSA failure risk was increased by 1.5- and 2.8-fold in men with 2 and 3 criteria, respectively. The RFS, but not the OS, was significantly different according to the preoperative score (P<.001). The postoperative score was significantly predictive for RFS and OS (P<.001 and P<.035, respectively). The risk of PSA failure was significantly increased with an increasing postoperative score (2-4.6-fold)., Conclusion: National data support evidence that RP can result in encouraging midterm oncologic outcomes for the management of high-risk PCa. At 5 years after surgery, 75% of patients remain disease free. Our easy-to-use risk stratification might help clinicians to better predict the clinical and PSA outcomes of high-risk patients after surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Prostate cancer is an important disease in terms of economic implications because of its increasing incidence and health care costs. We assessed the direct costs of the clinical management of prostate cancer in France. A retrospective study based on population-based data was carried out. Eight hundred and seventy-nine cases of prostate cancer diagnosed in five departments were included in a 5-year follow-up study. The economic analysis adopted the health-care payer's perspective and took into account only the direct costs. The mean cost of managing patients was estimated at euro12,731. It is composed of 49 to 82% of initial treatments according to the therapeutic strategy. The follow-up constituted between 3 and 11%, the costs of treatments for side effects between 1 and 3% and the travel cost between 3 and 7%. Cumulative total costs over 5 years for each treatment group showed variation in costs. Costs were highest for patients who were treated with external-beam radiotherapy and lowest for those with watchful waiting. The cost burden of prostate cancer is high and varies according to the treatment type. This study yielded a cost analysis of the different management practices of patients with prostate cancer.