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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.

Take Home Message Intervention-related deaths were rare in the ERSPC trial, but relatively large differences in the number of intervention-related deaths were observed among centers. Standardized cause-of-death reviews are important in identifying intervention-related deaths and should be used in screening trials., 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.

AIM: The French population is facing the COVID-19 pandemic and the health systems 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 [[[fr]]]Resume Objectif: La population francaise est confrontee a la pandemie de COVID-19 et le systemes de sante a ete reoriente en urgence pour la prise en charge des patients atteint du coronavirus La prise en charge des cancers de l'appareil urinaire et genital masculin doit etre adaptee a ce contexte Materiel et methode: Un avis d'experts documente par une revue de la litterature a ete formule par le Comite de Cancerologie de l'Association Francaise d'Urologie (CCAFU) Resultats: La prise en charge medicale et chirurgicale des patients atteint de cancers de l'appareil urinaire et genital masculin doit etre adaptee en modifiant les modalites de consultation, en priorisant les interventions en fonction du pronostic intrinseque des cancers en tenant compte des comorbidites du patient La protection des urologues vis-a-vis du COVID-19 doit etre prise en consideration CONCLUSION: Le CCAFU emet un avis d'experts quant aux mesures a prendre pour adapter la prise en charge des cancers de l'appareil urinaire et genital masculin au contexte de pandemie par COVID-19

352 Background: Active surveillance (AS) is a standard of care for low-risk prostate cancer (PC). However, 20 to 50% of patients (pts) will ultimately require a local treatment following AS. The aim of this study is to assess whether apalutamide could decrease the proportion of pts requiring local treatment within 3 years. We report the 1-year safety and quality of life analyses. Methods: multicentric phase II study conducted in patients with low to intermediate risk PC randomized between apalutamide 6 months (240 mg/d) with AS vs AS alone. Toxicity was evaluated each month during treatment and every 3 months thereafter for both arms. Quality of life (SF12) was assessed at baseline, 6 and 12 months post enrollment. Results: Patients were randomized: 51 in apalutamide and 40 in AS arm. Only 50 pts received apalutamide (one refusal). Median age was 64 yrs (47-76), median PSA 5.9 (1.5-21.5), only 2 pts had Gleason ISUP 2, 14% had >T2, the median cancer positive cores was 14.3%. The median testosterone level was 4.7 mg/l. Only 88 were available for safety analyses (48 in apalutamide arm). Maximal grades of reported adverse events during the first year were for the experimental arm: 25%, 56%, 19% and control arm: 20%, 15% 12.5% for G1, G2, G3 respectively. In the experimental arm, grade 1/2 related adverse events (AE) were cutaneous (25%) and HTA (15%), nausea 15%, diarrhea 10%, arthralgia or musculoskeletal event 17% and anemia 6%. Attention disorders were observed in 6% and hypothyroidism in 8%. The most frequent sexual dysfunctions were erectile dysfunction observed in 29% (7.5% in AS arm), gynecomastia in 60%, loss of libido in 21%, and nipple pain in 33%. One-year post enrollment, the testosterone level was 4.86 mg/l (1.5-9.8) vs 4.6 (2-7.7) in apalutamide and AS arm, respectively. Digestive symptoms were Grade 3. Related AEs were an HTA for 2 pts, rash for 1 pt, asthenia for 1 pt, erectile dysfunction for 1 pt, and decreased libido for 1 pt. One serious related AE was reported: grade 2 cerebral ischemic attack. A reduced dose was required for 16.67% of pts and 33.3% had transient discontinuation. The treatment was stopped for toxicity in 3 pts; 94% completed the 6 months of treatment. No differences were observed in physical component summary (PCS) and mental component summary (MCS) of SF12 for treatment vs AS at 6 mo (PCS: 55.1 vs 56.4; MCS 43.4 vs 41.4) and 12 mo (PCS: 53.6 vs 54.1; MCS 44.1 vs 42.9). Conclusions: This is a large randomized study evaluating apalutamide with active surveillance vs active surveillance. No new safety issues were observed and the safety profile was consistent relative to those previously described with apalutamide and castration, no falls or fracture were observed. No detrimental effect of apalutamide on QOL was observed during and after treatment. AEs are important for pts candidates for active surveillance. Clinical trial information: NCT03088124 .

INTRODUCTION AND OBJECTIVE:With a median follow–up of 16 years the European Randomized Study of Screening for Prostate Cancer (ERSPC) shows a relative reduction of prostate cancer (PCa) specific mo...

INTRODUCTION AND OBJECTIVE:Although HIFU treatment showed promising oncological results in several retrospective studies, large and comparative prospective studies are yet missing. The HiFi study (...

International audience

Introduction Voided urine cytology is a non-invasive method for diagnosing and following up on bladder carcinoma. But this exam suffers from low sensitivity and a lack of reproducibility due to pathologist examiner dependency, especially in low-grade tumours. Cystoscopy is chosen as the gold-standard exam, although it is considered aggressive by patients, especially when it is repeated. The aim of this study is to explore artificial intelligence (AI) to improve voided cytology. Material and method A national prospective multicentre trial (14 centres) was conducted on 1,360 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 focused 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 control. 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, respectively 84.9% vs. 43%. For high-grade tumours, VisioCyt test sensitivity was 92.6% compared to 61.1% for uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% versus 26.3% for uro-pathologists. Conclusion Compared to routine cytology, the first phase of VISIOCYT1 results shows very clear progress in term of sensitivity. It 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 artificial intelligence, it should become more and more efficient as more data is collected.

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. ispartof: EUROPEAN JOURNAL OF CANCER vol:146 pages:30-47 ispartof: location:England status: published

International audience; 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.

Circadian rhythms regulate several physiological functions and genes controlling the circadian rhythm were found to regulate cell proliferation, cell cycle and apoptosis. Few studies have investigated the role of those circadian genes in prostate cancer occurrence. We aim to investigate the relationship between circadian genes polymorphisms and prostate cancer risk based on data from the EPICAP study, a population-based case-control study including 1,515 men (732 cases / 783 controls) with genotyped data. Odds Ratios (ORs) for association between prostate cancer and circadian gene variants were estimated for each of the 872 single nucleotide polymorphisms (SNPs) in 31 circadian clock genes. We also used a gene-based and pathway-based approach with a focus on the pathway including 9 core circadian genes. Separate analyses were conducted by prostate cancer aggressiveness. The core-circadian pathway (p = 0.0006) was significantly associated to prostate cancer, for either low (p = 0.002) or high (p = 0.01) grade tumor. At the gene level, we observed significant associations between all prostate cancer and NPAS2 and PER1 after correcting for multiple testing, while only RORA was significant for aggressive tumors. At the SNP-level, no significant association was observed. Our findings provide additional evidence of a potential link between genetic variants in circadian genes and prostate cancer risk. Further investigation is warranted to confirm these findings and to better understand the biological pathways involved.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

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 16 yr 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 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), 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 20 ng/ml (9.9% compared with 4.1% in the second round, p

Background Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression.Methods Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients Results In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151).Conclusions Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not impact the quality of life of patients. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction.Trial registration: clinicaltrials.gov, NCT02854982. Registered 4 August 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02854982

ObjectiveTo investigate the role of night work in prostate cancer based on data from the EPICAP Study.MethodsEPICAP is a French population-based case-control study including 818 incident prostate cancer cases and 875 frequency-matched controls that have been interviewed face to face on several potential risk factors including lifetime occupational history. Detailed information on work schedules for each job (permanent or rotating night work, duration, total number of nights, length of the shift, number of consecutive nights) as well as sleep duration and chronotype, was gathered. Prostate cancer aggressiveness was assessed by Gleason Score.ResultsNight work was not associated with prostate cancer, whatever the aggressiveness of prostate cancer, while we observed an overall increased risk among men with an evening chronotype (OR=1.83, 95% CI 1.05 to 3.19). A long duration of at least 20 years of permanent night work was associated with aggressive prostate cancer (OR=1.76, 95% CI 1.13 to 2.75), even more pronounced in combination with a shift length >10 hours or ≥ 6 consecutive nights (OR=4.64, 95% CI 1.78 to 12.13; OR=2.43, 95% CI 1.32 to 4.47, respectively).ConclusionOverall, ever night work, either permanent or rotating, was not associated to prostate cancer. Nevertheless, our results suggest that a long duration of permanent night work in combination with a long shift length or at least six consecutive nights may be associated with prostate cancer, particularly with aggressive prostate cancer. Further studies are needed to confirm those findings.

Resume Contexte En France, la Haute Autorite de sante a rappele, en 2010, l’absence d’opportunite d’un depistage du cancer de la prostate (CaP) par le dosage du prostate-specific antigen (PSA) total. Objectif Ce travail a pour but de determiner les modes de prescription du dosage du PSA total ou du PSA libre (hors CaP) selon differents parametres et les montants rembourses. Methodes Les hommes de 40 ans et plus couverts par le regime general (73 % de la population francaise) entre 2012 et 2014 ont ete selectionnes. Les informations provenaient du systeme national d’information inter-regimes de l’Assurance maladie (Sniiram). Resultats En 2014, parmi les 11,6 millions d’hommes de 40 ans et plus, 27 % ont eu au moins un dosage du PSA total et 5,6 % au moins un dosage du PSA libre, avec de fortes variations selon l’existence ou non de symptomes urinaires du bas appareil (SBAU) traites (53 % et 15 % vs 24 % et 5 %) et interdepartementales. Le pic de prescription du PSA total culminait entre 65 et 74 ans : 64 % avec SBAU, 46 % sans SBAU. Entre 2012 et 2014, les hommes ayant realise au moins un dosage du PSA ont eu en moyenne 1,8 dosage du PSA total et 1,7 du PSA libre. En presence de SBAU, ces moyennes etaient respectivement de 2,3 et 2. Les medecins specialistes en medecine generale avaient prescrit 91 % des tests du PSA rembourses en 2014 (92 % pour le PSA total et 87 % pour le PSA libre) et les urologues 4 %. Le montant total rembourse etait de 28,5 millions d’euros dont 8,7 millions pour le PSA libre. En moyenne, 10 examens biologiques etaient realises le jour du dosage du PSA hors SBAU traitee. Conclusion Le nombre d’hommes realisant un dosage du PSA total est eleve comme pour le PSA libre dont l’utilite est discutee en premiere intention avant une biopsie. Ces dosages de PSA sont associes de nombreux autres examens biologiques a la recherche d’eventuelles anomalies, notamment chez les plus jeunes et pourraient en consequence ne pas faire l’objet d’une discussion specifique avec le patient sur leur pertinence.

RESUME Le concept des gestes robot assistes, qui ne se limite pas au tele-manipulateur Da vinci, envahit progressivement les blocs operatoires des pays industrialises. Dans un contexte budgetaire de plus en plus contraint, la chirurgie robot assistee avec le robot Da vinci s’est largement developpee en particulier pour les interventions urologiques. Les modifications induites par l’arrivee de cette innovation technologique assez revolutionnaire sont importantes, tant sur le plan technique pour l’equipe chirurgicale et paramedicale que sur le plan organisationnel et financier pour les structures de soins et pour notre systeme de sante. Cette publication qui reprend les principaux resultats oncologiques et fonctionnels des deux interventions pour lesquelles la chirurgie robot assistee s’est largement developpee en urologie (prostatectomie totale et chirurgie conservatrice du rein) , met en exergue les resultats encourageants mais le Service Medical Rendu considere comme faible dans le rapport de la Haute Autorite de Sante de novembre 2016 sur la dimension clinique et organisationnelle de la chirurgie robot assistee pour la prostatectomie totale souleve encore de nombreuses interrogations face au developpement inexorable de cette technologie qui prend le pas sur les autres voies d’abord. Nous proposons dans ce document de donner quelques reponses a vos interrogations sur « l’explosion » de cette technologie en urologie.

Background Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression. Methods Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients Results In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151). Conclusions Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients Trial registration clinicaltrials.gov, NCT02854982. Registered 4 August 2016, retrospectively registered.

International audience; Over the past two decades, several studies have attempted to understand the hypothesis that disrupting the circadian rhythm may promote the development of cancer. Some have suggested that night work and some circadian genes polymorphisms are associated with cancer, including prostate cancer. Our study aims to test the hypothesis that prostate cancer risk among night workers may be modulated by genetic polymorphisms in the circadian pathway genes based on data from the EPICAP study, a population-based case-control study including 1511 men (732 cases/779 controls) with genotyped data. We estimated odds ratio (ORs) and P values of the association between prostate cancer and circadian gene variants using logistic regression models. We tested the interaction between circadian genes variants and night work indicators that were significantly associated with prostate cancer at pathway, gene and SNP levels. Analyses were also stratified by each of these night work indicators and by cancer aggressiveness. The circadian pathway was significantly associated with aggressive prostate cancer among night workers (P =.004), particularly for men who worked at night for 10 hours, P =.001). At the gene level, we observed among night workers significant associations between aggressive prostate cancer and ARNTL, NPAS2 and RORA. At the SNP-level, no significant association was observed. Our findings provide some clues of a potential modulating effect of circadian genes in the relationship between night work and prostate cancer. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.

Elevated body mass index (BMI) has been inconsistently associated with prostate cancer occurrence but it has been suggested that life course adulthood obesity may be associated with an increased risk of prostate cancer. However, few studies have investigated lifetime BMI and prostate cancer risk. We analyzed life course BMI trajectories on prostate cancer risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). We included in our analyses 781 incident prostate cancer cases and 829 controls frequency matched by age. Participants were asked about their weight every decade from age 20 to two years before reference date. BMI trajectories were determined using group‐based trajectory modeling to identify groups of men with similar patterns of BMI changes. We identified five BMI trajectories groups. Men with a normal BMI at age 20 developing overweight or obesity during adulthood were at increased risk of aggressive prostate cancer compared to men who maintained a normal BMI. Our results suggest that BMI trajectories resulting in overweight or obesity during adulthood are associated with an increased risk of aggressive prostate cancer, particularly in never smokers, emphasizing the importance of maintaining a healthy BMI throughout adulthood., The influence of body weight during lifetime on PCa risk remains largely ununderstood and has been poorly investigated. Our findings suggest that elevated BMI during adulthood resulting in overweight or obesity is associated with an increased risk of aggressive PCa, emphasizing the importance of maintaining a healthy BMI throughout adulthood.

Background High body mass index (BMI) has been inconsistently associated with prostate cancer (PCa) risk. Recent studies suggest that BMI trajectory modeling provides a more robust substitute method to predict cancer risk compared to static measures of BMI. However, only four studies have investigated lifetime BMI and PCa risk. We analyzed the effects of life course BMI trajectories on PCa risk based on data from the Epidemiological study of Prostate Cancer (EPICAP). Methods EPICAP is a French population-based case-control study that enrolled 819 incident cases of PCa diagnosed in 2012 and 2013, aged less than 75 years old and residing in the departement of Herault, France. Controls were 879 age-matched men living in the same geographic area. Face to face interviews, using a standardized computerized questionnaire, gathered information about socio-demographic characteristics, medical history, lifestyle factors, physical activity, residential and occupational history. Anthropometric indicators have been collected through the questionnaire (self-report of height at 18 years old and weight every decades) or anthropometric measures at time of interview (height, weight, waist and hip circumferences). BMI trajectories were determined using group-based trajectory modeling to identify groups of men with similar patterns of BMI change through adulthood. Logistic regression models were used to assess odds ratios (ORs) for the associations between BMI trajectories and PCa risk. Analyses were systematically adjusted for age, family history of PCa and ethnicity. Stratified analyses were conducted by PCa aggressiveness according to the Gleason score. Seeking for relevant interaction between smoking status and BMI trajectories and given that smoking is a major risk factor for many types of cancer, known to decrease obesity, we performed stratified analyses according to smoking status. Results We identified four BMI trajectories groups: ‘stable normal BMI’ (29.7%), ‘normal BMI to overweight’ (50.7%), ‘normal BMI to obesity’ (17.4%) and ‘overweight to obesity’ (2.2%). Men who had a BMI in the normal range at age 20 and developed overweight through adulthood had an increased risk of overall (OR 1.27, [0.99–1.62]) and aggressive (OR 1.57, [1.03–2.39]) PCa risk compared to men who maintained a normal BMI. Increased risk of aggressive PCa was also observed among never smokers who developed overweight (OR 3.32, [1.29–8.53]) or obesity (OR 4.19, [1.30–13.51]), but interaction was not significant. Conclusion Our results suggest that BMI trajectories resulting in overweight or obesity during adulthood are associated with an increased risk of PCa, emphasizing the importance of maintaining a normal BMI throughout adulthood for cancer prevention.

Background Obesity is associated with an increased risk of several cancers, but the relationship between obesity and prostate cancer (PCa) remains controversial. We showed than body mass index (BMI) itself is not associated with PCa, while central obesity indicators, such as waist circumference (WC) or waist-hip ratio (WHR), were associated with increased risks of PCa. To further explore this relationship and given the accumulating evidence between BMI and smoking in cancer risk, we conducted further analyses taking into account smoking status within the EPICAP study. Methods EPICAP is a French population-based case-control study that enrolled 819 incident cases of PCa diagnosed in 2012 and 2013, aged less than 75 years old and residing in the departement of Herault, France. Controls were 879 age-matched individuals living in the same geographic area. Face to face interviews, using a standardized computerized questionnaire, gathered information about socio-demographic characteristics, personal medical history, lifestyle factors, physical activity, residential and occupational history. Anthropometric indicators have also been collected through the questionnaire (self-report of height at 18 years old and weight every decades) or anthropometric measures at time of interview (height, weight, waist and hip circumferences). Logistic regression models were used to assess odds ratios (ORs) for the associations between anthropometric indicators (BMI, WC, WHR) and PCa risk. Analyses were adjusted for age, family history of PCa and ethnicity. Stratified analyses were conducted by PCa aggressiveness according to the Gleason score. Seeking for relevant interaction between smoking status and BMI trajectories and given that smoking is a major risk factor for many types of cancer, known to decrease obesity, we performed stratified analyses according to smoking status. Results Overall, 28.6% were never smokers, 54.9% former smokers, and 16.5% current smokers, similarly distributed between cases and controls (p=0.21). Among never smokers, we observed a slight but not significant increased risk of overall PCa for men with a BMI above 25 kg/m2; (OR 1.52 [0.97–2.38]) as well as for men with a WC greater to 94 cm (OR 1.42 [0.93–2.16]) or a WHR greater or equal to 0.95 (OR 1.40 [0.92–2.13]). Among current smokers, we observed no association between BMI, WC or WHR and PCa risk (OR 1.15 [0.62–2.13], OR 1.24 [0.68–2.30], OR 1.06 [0.58–1.93], respectively). However interaction was not significant. Conclusion Our results showed that associations between anthropometric indicators were more pronounced among never smokers, in agreement with the assumption that smoking may attenuate the association between obesity and cancer.

Contexte L’acetate d’abiraterone en association avec la prednisone/prednisolone et le docetaxel peuvent etre utilises en premiere ou en deuxieme intention dans le traitement du cancer de la prostate resistant a la castration et metastatique (mCRPC). Objectifs Evaluer si le fait de commencer par une premiere ligne de traitement d’acetate d’abiraterone suivie d’une deuxieme ligne de docetaxel (sequence ABI–DOCE) ou d’utiliser la sequence de traitement inverse DOCE–ABI a un impact sur la survie des patients mCRPC en situation reelle de soins. Methodes Il s’agit d’une etude de cohorte a partir du Systeme National des Donnees de Sante (SNDS) couvrant environ 86 % de la population au moment de l’etude : les patients mCRPC ont ete identifies en 2014 comme initiant la sequence de traitement ABI–DOCE ou DOCE–ABI avec un suivi de 3 ans. Les patients avec la sequence ABI–DOCE et ceux avec DOCE-ABI ont ete apparies 1 : 1 sur le stade de la maladie avant le statut mCRPC, l’anciennete du cancer de la prostate, et un score de propension a haute dimension. La survie globale ainsi que la survie jusqu’au changement de traitement ou au deces (proxy de la survie sans progression) a 36 mois ont ete comparees a l’aide de modeles de Cox multivaries. Resultats Sur les 3949 patients mCRPC ayant initie un traitement de premiere intention en 2014, 1162 sont decedes au cours de cette premiere ligne et 2283 ont beneficie d’un traitement de deuxieme ligne. Parmi ces derniers, 693 ont recu la sequence ABI–DOCE et 354 DOCE–ABI. Au total, 159 patients par groupe etaient apparies 1 : 1. La duree mediane de la premiere ligne de traitement etait de 8,4 mois dans la sequence ABI–DOCE et de 6,6 mois dans la sequence DOCE–ABI. La duree mediane de la deuxieme ligne etait respectivement de 6,3 mois et 6,5 mois dans les sequences ABI–DOCE et DOCE–ABI. Environ 60 % des patients ont recu une troisieme ligne de traitement dans les deux groupes. Les probabilites de survie globale a 36 mois etaient de 33,8 % [27,4 - 41,7] pour ABI–DOCE et 34,4 % [7,8 - 42,5] pour DOCE–ABI avec des medianes de survie de respectivement 26,2 mois [22,2 - 29,8] et 26,6 mois [22,6 - 30,5] (valeur de p : 0,91). Les probabilites de survie jusqu’au changement de traitement ou au deces a 36 mois etaient de 13,7 % [9,6 - 19,7] pour ABI-DOCE et 9,9 % [6,4 - 15,1] pour DOCE–ABI avec des medianes de survie de respectivement 17,5 mois [15,4 - 18,9] et 16,1 mois [14,5 - 17,6] (valeur de p : 0,1983). Conclusion En situation reelle de soins, les sequences de traitement (ABI–DOCE versus DOCE–ABI) semblent n’avoir aucun impact differentiel sur les resultats de survie chez les patients mCRPC partageant les memes caracteristiques.

Resume Introduction Un nombre important de patients atteints d’un cancer de la prostate (CP) est diagnostique et traite. L’objectif de cette etude est d’analyser, deux ans apres traitement, l’incontinence urinaire (IU) et les dysfonctionnements sexuels (DS) pouvant affecter les patients. Methodes Cette etude a suivi tous les cas de CP localise, diagnostiques entre 2008–2009, chez les hommes d’âge ≤ 65 ans en vie deux ans apres traitements. Quatre cent trente-sept personnes ont ete incluses dans l’enquete. Les donnees ont ete collectees par un questionnaire et par croisement avec les donnees du registre des cancers. Une analyse descriptive et comparative de la persistance des sequelles a deux ans a ete effectuee. Resultats A deux ans du traitement, l’IU a persiste pour 48,8 %, 41,2 % ont eu recours a des protections urinaires ; 39,2 % portaient au moins une protection/jour ; 55,2 % ont eu des difficultes financieres a l’achat des protections. Au total, 22,7 % n’ont pas consulte de specialiste pour l’IU. Les DS ont persiste pour 82,8 % ; 30,4 % n’ont pas consulte de specialiste. Les DS ont eu un impact negatif sur la vie sexuelle des patients et de leurs partenaires. Apres ajustement sur le stade, seule la prostatectomie est significativement associee a la persistance de l’IU et de la DS. Conclusion Le pourcentage de patients ayant une IU et/ou une DS persistante reste eleve. La persistance de ces sequelles a ete associee a la prostatectomie. Les differences de toxicites entre traitements doivent etre presentees aux patients avant toute prise en charge afin d’engager le patient dans une demarche de decision partagee.

91 Background: Abiraterone acetate in association with prednisone/prednisolone and docetaxel can both be used as first or second line treatments for metastatic castration-resistant prostate cancer (mCRPC). As a result, one may wonder if it is better to start with an abiraterone acetate first line followed by a docetaxel second line (ABI–DOCE sequence) or to use the inverse sequence DOCE-ABI. Methods: A new user cohort study design with a 3-year follow-up: patients initiating a first-line treatment for mCRPC in 2014 followed by a second treatment line were identified from the French nationwide claims database (SNDS), which covers about 86% of the population at the time of the study. Patients with sequence ABI–DOCE and those with DOCE-ABI were 1:1 matched on prostate cancer stage before mCRPC status, duration from prostate cancer diagnosis, and a high-dimensional propensity score. The 36-month overall survival and the 36-month survival time until treatment switch or death (proxy of progression-free survival) were compared using Cox proportional hazards risk model. Results: Out of the 3 949 mCRPC patients that initiated a first-line treatment in 2014, 1 162 died during this first line, and 2 283 had a second-line treatment. Among them, 693 received the sequence ABI–DOCE and 354 DOCE–ABI. A total of 159 patients per group were 1:1 matched. The median duration of the first treatment line was 8.4 months in the ABI–DOCE sequence and 6.6 months in the DOCE–ABI sequence. The median duration of the second line was 6.3 months and 6.5 months in the ABI–DOCE and DOCE–ABI sequences, respectively. Results are presented in the table below. Median survivals were similar in both groups with no significant differences observed in the 36-month survival probabilities. Around 60% of the patients received a third-line treatment in both groups. Conclusions: In real life settings, treatment sequences (ABI–DOCE versus DOCE–ABI) seem to have no differential impact on survival outcome in mCRPC patients sharing same characteristics. [Table: see text]

5570 Background: Therapeutic strategy in metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly with the introduction of abiraterone acetate in association with prednisone/prednisolone in first-line treatment in December 2012. This work aimed to compare the effectiveness of abiraterone acetate and docetaxel as first-line treatments for mCRPC, in real-life setting. Methods: Patients with mCRPC were identified in the main scheme of the National Healthcare System database (SNDS), which covers about 86% of the French population, and capturing all reimbursed healthcare expenditures and hospital discharge summaries. Those initiating docetaxel or abiraterone acetate in 1st line in 2014 were included and 1:1 matched on the previous prostate cancer stage before mCRPC status, the delay from the date of initial diagnosis and a high-dimensional propensity score. The 36-month overall survival and the 36-month discontinuation-free survival (i.e. survival time until treatment switch or death) were compared using Cox proportional hazards risk model. Results: In 2014, out of the 12,951 patients with prevalent mCRPC, 1,214 initiated docetaxel in 1st line and 2 444 initiated abiraterone. A total of 716 patients per group were matched with good comparability (C-statistic = 0.6). The median duration of docetaxel–defined as the time between the first and the last infusion–was 7.3 months with a median of 6 infusions. The median duration of abiraterone acetate–corresponding to the period covered by the dispensed drug–was 9.1 months. Near 70% of the docetaxel and 62% of the abiraterone acetate patients received a 2nd line of treatment. Results related to the main survival outcomes are presented in the table below. Conclusions: First-line treatment with abiraterone acetate in mCRPC patients results in a better 36-month overall survival and discontinuation-free survival compared to docetaxel in real-life setting. [Table: see text]

IF 3.636 (2017); International audience; 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.

// Pierre-Jean Lamy 1, 2 , Brigitte Tretarre 3 , Xavier Rebillard 1 , Marie Sanchez 4 , Sylvie Cenee 4 and Florence Menegaux 4 1 Service Urologie, Clinique Beau Soleil, Montpellier, France 2 Institut d’Analyse Genomique-Imagenome, Labosud, Montpellier, France 3 Registre des Tumeurs de l’Herault, ICM, Montpellier, France 4 Universite Paris-Saclay, Universite Paris-Sud, CESP (Center for Research in Epidemiology and Population Health), Inserm, Team Cancer and Environment, Villejuif, France Correspondence to: Pierre-Jean Lamy, email: pierre-jean.lamy@labosud-ocbiologie.fr Keywords: family history of cancer; epidemiology; prostate cancer; breast cancer; Gleason score Abbreviations: BCa: breast cancer; GS: Gleason score; OR: Odd ratio; PCa: prostate cancer Received: March 01, 2018 Accepted: April 17, 2018 Published: May 04, 2018 ABSTRACT 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.

Objectifs La cytologie urinaire mictionnelle (CUM) est non invasive, mais souffre d’un manque de sensibilite et reste pathologiste dependante, notamment dans les lesions urotheliales de bas grade. Afin d’ameliorer le diagnostic sur les urines, VitaDX a developpe dans le cadre de l’essai clinique VISIOCYT un dispositif medical qui utilise des algorithmes de traitement d’image et de machine learning (IA) pour predire le caractere tumoral des CUM. Methodes VISIOCYT est une etude clinique prospective multicentrique, portant sur 1360 patients repartis en deux groupes : les temoins negatifs (TNeg) confirmes par une CUM et une endoscopie negatives et les patients porteur d’une tumeur urotheliale (PTU) par le resultat d’une histologie positive de carcinome urothelial. Les resultats de cette communication portent sur 586 patients ; 127 TNeg et 459 PTU (242 haut grade et 217 bas grade). Les performances ont ete evaluees par validation croisee, une approche statistique standard en IA. Les 586 patients ont donc ete subdivises aleatoirement 42 fois dans les proportions suivantes : 5/6 des donnees pour l’apprentissage et 1/6 pour l’evaluation. Resultats A l’issue de la validation croisee, les mesures de performance obtenues sur chacune des 42 partitions sont moyennees pour evaluer les performances de l’algorithme. La sensibilite moyenne de l’algorithme est de 82,6 % pour une specificite de 71,4 %. En detail, on observe une sensibilite moyenne de 89,3 % pour les diagnostics de haut grades et de 76,4 % pour les diagnostics de bas grade. Sur les memes partitions, a titre de comparaison, la sensibilite moyenne des praticiens de l’essai clinique est de 43 % sur l’ensemble des malades, avec en particulier une sensibilite de 61,1 % pour les haut grades et de 26,3 % pour les bas-grades. La specificite des praticiens est par defaut de 100 % car la cytologie negative est un critere d’inclusion pour le groupe temoin ( Tableau 1 ). Conclusion L’approche algorithmique (IA) semble permettre un meilleur diagnostic des lesions urotheliales de bas grade par rapport a la CUM traditionnelle. Ces resultats devront etre confirmes a l’issu de l’essai clinique en sachant que les performances devraient augmenter avec l’accumulation de donnees supplementaires.

Introduction Obesity is associated with an increased risk of several cancers, such as breast or colorectal cancers. However, the relationship between obesity and prostate cancer (PCa) remains controversial. Indeed, inconsistent results have been reported between body mass index (BMI) and PCa risk, while some associations have been reported with other anthropometric indicators, such as waist circumference (WC) or waist-hip ratio (WHR), which would better illustrate the concept of body fat distribution. Therefore, we assessed a possible association between anthropometric indicators and PCa risk based on data from the EPICAP study. Methods EPICAP in a French population-based case-control study that enrolled 819 incident cases of PCa diagnosed in 2012 and 2013, aged less than 75 years old and residing in the department of Herault, France. Controls were 879 age-matched (± 5 y) individuals living in the same geographic area. Face-to-face interviews, using a standardized computerized questionnaire, gathered information about sociodemographic characteristics, personal medical history, lifestyle factors, physical activity, residential and occupational history. Anthropometric indicators have also been collected through the questionnaire (self-report of height at 18 years old and weight every decades) or anthropometric measures at time of interview (height, weight, waist and hip circumferences). Logistic regression models were used to assess odds ratios (ORs) for the associations between anthropometric indicators (BMI, WC and WHR) and PCa risk. Analyses were systematically adjusted for age (5-year period), family history of prostate cancer in first-degree relatives and race (Caucasians, others). Analyses were also adjusted for other potential confounding factors such as educational level or physical activity. Separate analyses were conducted by prostate cancer aggressiveness according to the Gleason score (low or intermediate score ≤ 7 [including 3 + 4], high score ≥ 7 [including 4 + 3]). Seeking for relevant interaction between BMI and WC or WHR, we performed stratified analyses according to BMI overweight cut-point (25 kg/m2) defined by the World Health Organization. Results Overall, 47.8% of men were overweight and 23.4% were obese, similarly distributed between cases and controls (OR 0.98, 95% CI 0.78–1.23, OR 0.91 95% CI 0.67–1.23, respectively). We observed a slight, but not significant increased risk of PCa for men with a WC above 94 cm (OR 1.20, 95% CI 0.95–1.51) and an increased risk of PCa for men with a WHR greater or equal to 0.95 (OR 1.27, 95% CI 1.01–1.60), with more pronounced associations after adjustment for BMI (OR 1.48, 95% CI 1.11–1.97, OR 1.39, 95% CI 1.09–1.79, respectively). In addition, analyses stratified on BMI showed that men with a BMI 94 cm or WHR ≥ 0.95 (OR 1.63, 95% CI 1.05–2.52, OR 1.76, 95% CI 1.18–2.63, respectively). Nevertheless, interactions were not significant for WC (P = 0.23) and close to significance for WHR (P = 0.07). Associations regarding central obesity indicators, adjusted for BMI, were more pronounced in men with aggressive prostate cancer, either for WC > 94 cm (OR 2.30, 95% CI 1.38–3.83) or WHR ≥ 0.95 (OR 1.51, 95% CI 0.98–2.32). Conclusions Our results suggest that BMI itself is not associated with prostate cancer, while central obesity is associated with an increased risk of prostate cancer, especially aggressive prostate cancer.

International audience; 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.

International audience; 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

Background In 2007, the International Agency for Research on Cancer classified ”shift work leading to a disruption of circadian rhythm” as probably carcinogenic to humans based on sufficient evidence from experimental animal models but limited evidence from epidemiological studies in humans. In this context, we investigated the role of night shift work in prostate cancer based on data from the EPICAP study. Methods EPICAP is a French population-based case-control study including 819 incident prostate cancer cases and 879 frequency matched controls. Cases and controls were face-to-face interviewed on their lifetime occupational history with details on work schedules for each job held for ≥6 months. Night work was defined as having performed permanent or rotating night shifts for at least 270 hours/year or 3 nights/month during ≥1 year. Results Permanent and rotating night work were not associated with prostate cancer (OR=0.99 [0.78–1.26], OR=0.89 [0.66–1.20], respectively]). However, permanent night work was associated with aggressive prostate cancer (OR=1.40 [0.97–2.03]), especially for a duration greater than 25 years (1.89 [1.15–3.11]). Interestingly, an association between night work and prostate cancer risk was observed for men with an evening chronotype (OR=1.82 [1.01–3.28]), especially for rotating night work (OR=2.34 [1.02–5.35]). Conclusion Our results suggest that night work may be associated with prostate cancer, particularly in men with aggressive prostate cancer or with an evening chronotype. Further investigations are needed to confirm our findings and to take into account a potential influence of an individual susceptibility to circadian genes in this association.

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.

International audience; 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.

International audience; 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.

Objectif La prise en charge du cancer de la prostate metastatique resistant a la castration (mCRPC) a fortement evolue depuis 2011. L’etude CAMERRA vise a decrire cette evolution via l’identification des cas prevalents de mCRPC dans le SNDS. En l’absence de marqueur direct du mCRPC au sein du SNDS, l’identification des cas necessite la construction d’un algorithme complexe. Methodes Un algorithme d’identification des patients mCRPC a ete construit a partir d’une extraction d’hommes âges de plus de 40 ans, couverts par le Regime general de l’Assurance maladie, avec un indicateur de cancer de la prostate (ALD, hospitalisations et actes CCAM, medicaments) et disposant d’un historique de soins de cinq ans sans absence de remboursement > 1 an. L’identification des mCRPC repose sur la construction de deux indicateurs : la date de premiere prise en charge des metastases se basant sur des actes specifiques (radiotherapie, hospitalisations, traitements ciblant les metastases [denosumab, acide zoledronique, radio-isotopes, radiofrequences, etc.], et des traitements specifiques du mCRPC (acetate d’abiraterone, enzalutamide, docetaxel et cabazitaxel) associes a des actes d’imageries ; la date de resistance a la castration s’appuyant sur les changements entre les sequences de traitements par anti-androgenes et analogues de la LH-RH, les actes chirurgicaux (orchidectomie et pulpectomie) ou la premiere delivrance d’estramustine ou d’un traitement specifique du mCRPC. Un patient est considere comme mCRPC a partir du moment ou il dispose d’une date de premiere prise en charge des metastases et d’une date de resistance a la castration. Resultats En 2014, 3192 patients avec un cancer de la prostate ont ete identifies dans l’EGB, parmi lesquels 499 metastatiques et 254 resistants a la castration. Chez ces 3192 patients, 141 ont ete identifies comme ayant un mCRPC. Par extrapolation, 468 142 cancers de la prostate sont attendus dans le SNDS en 2014. Cette estimation concorde avec celle de l’Institut national du cancer (INCa) : 508 699 en 2008. Parmi ces cas prevalents de cancer de la prostate, 20 137 devraient etre des mCRPC. Conclusion Cette etude preliminaire a permis de construire un algorithme fonctionnel d’identification des mCRPC en tenant compte d’elements complexes et de leur sequence, permettant une premiere estimation de la prevalence des mCRPC dans la population francaise d’apres le SNDS. La prise en charge des patients selectionnes sera par la suite decrite afin de rendre compte de l’evolution du parcours de soin.

Objectifs Le cancer de la prostate est le 1er cancer chez l’homme. Il peut evoluer vers un stade metastatique et resistant a la castration (mCRPC). Tres peu de donnees epidemiologiques sont disponibles sur le mCRPC. La base du Systeme national des donnees de sante (SNDS) couvrant l’ensemble de la population francaise offre les informations medicales individuelles necessaires pour estimer la prevalence et l’incidence du mCRPC. Methodes Un algorithme visant a identifier les patients ayant un mCRPC en 2014 parmi les hommes de plus de 40 ans affilies au regime general, a ete developpe, valide et applique dans le SNDS sur la periode 2009–2016. La date de resistance a la castration et la date de premiere prise en charge des metastases ont ete estimees en se basant sur les actes medicaux (prostatectomie, radiotherapie, etc.), les diagnostics hospitaliers, la realisation d’examen medicaux, et les dispensations et administration de medicaments captures dans le SNDS (hormonotherapie classique et de nouvelle generation, chimiotherapie, etc.). Les resultats ont ete extrapoles a l’ensemble de la population francaise. Resultats En 2014, le nombre estime de cas prevalents de cancer de la prostate etait de 488 618 dont 36 590 metastatiques (7,5 %) et 24 096 resistants a la castration (4,9 %), pour un total de 16 423 mCRPC (3,4 %). Dans 52 % des cas, la resistance a la castration et la prise en charge des metastases ont ete detectees dans un intervalle de 4 mois. Les metastases ont precede de plus de 4 mois la resistance a la castration dans 30 % des cas. Les mCRPC incidents etaient 5561 en 2014. Au 31/12/2014, la prevalence partielle a 5 ans du cancer de la prostate etait de 185 322 et de 3596 chez les mCRPC. Conclusion La richesse des donnees du SNDS a permis la mise en œuvre d’un algorithme complexe capable d’identifier les patients mCRPC et d’actualiser les donnees epidemiologiques associees.

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.