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Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Targeted antibiotic prophylaxis (TAP) is required for patients with positive urine culture before urological surgery. Our aim was to determine the efficacy of TAP. This was a prospective single-center study performed in a urology department. All patients who underwent a programmed surgery were included. Urine culture was obtained before surgery requiring a prophylaxis: in the case of sterile urines, antibiotics were used in accordance with national recommendations; for positive urine culture, a TAP was used in accordance with susceptibility testing. The drugs were administered for 2 days before surgery until withdrawal of bladder catheter. The occurrence of healthcare-associated infections was registered until day 30 after surgery. Two hundred three patients were included for 8 non-consecutive weeks in 2020, among whom fifteen were lost of sight before day 30. Among the remaining 188 patients, most frequent surgeries were 75 prostatic diseases (40%), 50 endo-ureteral surgeries for JJ stent insertion (27%), and 23 bladder cancers (12%). One hundred forty-eight (79%) patients required a urine culture before procedure; 142/148 (96%) urine cultures were performed, leading to 74 TAP. The main isolated bacteria were 48 Enterobacteriaceae and 8 Enterococcus spp. TAP was cotrimoxazole (n = 30), aminoglycosides (n = 11), amoxicillin (n = 9), fluoroquinolones (n = 7), and others (n = 17). The rate of healthcare-associated infections was 14.8% (11/74), including six microbiologically documented antibiotic failures. The rate of healthcare-associated infection after urological surgery using TAP was high, implying to discuss the choice and the dosage of the antibiotic molecules.

Resume Introduction Les ultrasons focalises de haute intensite (HIFU) ont montre leur efficacite dans le traitement des cancers localises de la prostate. Le but de cette etude prospective est d’en evaluer leurs premiers resultats carcinologiques et fonctionnels au sein d’une population afro-caribeenne. Materiel et methodes De mai 2018 a janvier 2020, 77 patients afro-caribeens ont ete inclus. Plusieurs traitements etaient realises : total, hemi-ablatif ou focal ; en premiere intention (groupe I), ou en traitement de rattrapage (groupe II). Des PSA etaient doses a 2, 6, 9 et 12 mois. Une IRM prostatique et des biopsies consecutives etaient effectuees entre 6 et 9 mois postoperatoires. La continence, la dysurie et la fonction erectile etaient evaluees a 6 mois (questionnaires ICS, IPSS et IIEF). Resultats Le groupe I incluait 71,2 % des patients, le groupe II, 28,8 %. L’âge median etait de 75,4 ans [IQR 69,6–79,4]. Le suivi median etait de 8,3 mois [IQR 3,5–12,25]. Le PSA median a l’inclusion etait de 7,7 ng/ml [IQR 5,5–11,2] dans le groupe I, et de 5,9 ng/ml [IQR 4,4–7,9] dans le groupe II. Toutes populations confondues, les biopsies etaient negatives dans 73,5 % des cas ; 14,7 % des biopsies etaient positives en zone traitee et 11,8 % en zone non traitee. Concernant les morbidites, 7,5 % des patients ont developpe une incontinence urinaire et le taux de dysfonction erectile etait de 13,2 %. Conclusion Cette etude marque les debuts de l’experience de l’HIFU Focal One® dans une population afro-caribeenne. Ce traitement semble sur et reproductible avec des resultats carcinologiques satisfaisants et une faible morbidite genito-urinaire. Un suivi a plus long terme et un effectif de patients plus important sont necessaires pour valider ces resultats. Niveau de preuve III.

Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries.Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.1% of cases with an African origin.Forty-seven germline mutations in 11 DDR genes were identified in 46 patients of the total cohort (8.3%). BRCA2 (4.1%) and ATM (2.0%) were the most frequently mutated genes. There was no difference in DDRg mutation frequency between mPC patients of European ancestry and those of African origin. Germline mutations of BRCA2 were associated with a positive family history of breast cancer (p = 0.02). The mean age at metastatic stage (59.7 vs. 67.0; p = 0.0003) and the mean age at death (65.2 vs. 73.9; p = 0.0003) were significantly earlier for carriers of BRCA2 mutation than for non-carriers. Moreover, the Cox model showed that BRCA2 positive status was statistically associated with poorer survival (hazard ratio: 0.29; 95% confidence interval 0.18-0.48; p 0.0001).We showed that, in France, BRCA2 and ATM are the main predisposing DDR genes in mPC patients, with a particular aggressiveness for BRCA2 leading to early metastatic stage and death.

International audience; Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age

International audience; Although several studies have examined the relationship between organochlorine pesticides (OCPs) and prostate cancer (PCa) risk, no data are available concerning the association between OCPs concentrations in periprostatic adipose tissue (PPAT), which reflects cumulative exposure, and PCa aggressiveness. Moreover, no previous study has compared OCPs exposure in two distinct ethno-geographical populations. The objectives were to analyze OCPs in PPAT of PCa patients from either Mainland France or French West Indies in correlation with features of tumor aggressiveness, after adjusting for potential confounders such age, BMI, and polyunsaturated fatty acid (PUFA) content of PPAT. PPAT was analyzed in 160 patients (110 Caucasians and 50 African-Caribbeans), 80 with an indolent tumor (ISUP group 1 + pT2), and 80 with an aggressive tumor (ISUP group more than 3 + pT3). The concentrations of 29 OCPs were measured in PPAT concomitantly with the characterization of PUFA content. Exposure patterns of OCPs differed according to the ethno-geographical origin. Most OCPs were found at higher concentration in Caucasian patients, whereas pp’-DDE content was twice as high in African-Caribbeans. Chlordecone was only detected in PPAT from African-Caribbean patients. Most OCP concentrations were positively correlated with age, and some with BMI. After adjusting for age, BMI, and PUFA composition of PPAT, no significant association was found between OCPs content and risk of aggressive disease, except of mirex which appeared inversely associated with aggressive features of PCa in Caucasian patients. These results highlight a significant ethno-geographic variation in internal exposure to OCPs, which likely reflects differences in consumption patterns. The inverse relationship observed between mirex concentration and markers of PCa aggressiveness need to be further investigated.

International audience; BACKGROUND:Several studies in the Caucasian population have shown that patients with Gleason 6 prostate cancer, based on surgical specimens, have low or no risk of metastasis. However, there is no data for men of African ancestry. The objective of this study was to estimate the overall, specific, and metastasis-free survival (MFS) of patients with a Gleason 6 score, based on the surgical specimen.PATIENTS AND METHODS:This was a monocentric retrospective study that included 723 consecutive patients treated by radical prostatectomy between 1 January 1 2000 and 31 March 2018, with a Gleason score of 6 based on the surgical specimen. Specific survival (SS) was defined as the time elapsed between surgery and death attributed to prostate cancer. Overall survival was defined as the time elapsed between surgery and death from all causes. The causes of death were verified in the medical records. Survival analyses without biochemical recurrence (BCR) and without salvage treatment were performed according to the Kaplan-Meier method. The Cox model was used for univariate and multivariate analyses.RESULTS:In total, 691 patients were included because 32 were excluded for missing data. Overall 5- and 10-year survival was 94.2% and 87.1%, respectively. SS and MFS were 100%, with a median follow-up of 8.5 years. The BCR rate was 16.5%, with a median time to BCR of 5.1 years. The frequency of salvage treatment was 13.0%, with a median time to surgery of 7.3 years. In univariate analysis, PSA, pathological stage, seminal vesicle invasion, positive margins, and lymph node dissection were significantly associated with an increased risk of BCR and salvage treatment, but only PSA and positive margins were significantly associated by multivariate analysis.DISCUSSION/CONCLUSION:No metastasis or disease-specific deaths were observed for men with Gleason score ≤6 prostate cancer at radical prostatectomy, in particular, men of African ancestry.

International audience; INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a group of risk factors that increases the likelihood of developing cardiovascular diseases. Although suggested, the relationship between MetS and prostate cancer (PCa) is still inconclusive. Very few studies have addressed this question in populations of African descent, which are disproportionately affected by PCa. This study aimed to assess the prevalence of MetS among incident cases of Afro-Caribbean PCa and estimate its association with adverse clinicopathological features and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: We included 285 consecutive patients with incident cases of PCa attending the University Hospital of Guadeloupe (French West Indies). MetS was evaluated at the time of diagnosis by collecting information on blood pressure, glycaemic status, triglyceride and high-density lipoprotein cholesterol levels, and obesity through various surrogates, including two waist circumference indicators (≤94 cm, ≥102 cm), the waist-to-hip ratio (≥0.95), and body mass index (BMI; ≥30 kg/m(2) ). We followed 245 patients who underwent RP as primary treatment of localized PCa. RESULTS: The prevalence of MetS varied greatly, from 31.6% to 16.4%, when a waist circumference ≥94 cm or BMI were used as obesity surrogates, respectively. No significant associations were found between MetS, regardless of the obesity criteria employed, and the risk of adverse pathological features or BCR. CONCLUSIONS: The high variability in MetS resulting from the diversity of obesity criteria used may explain the discordant associations reported in the literature. Further studies using strict and uniform criteria to define MetS on homogeneous ethnic groups are encouraged to clarify the association, if any, between MetS and PCa outcomes.

Background Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations. Methods We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included. Results Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first. Conclusion Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.

International audience; Introduction Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration-resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression-free survival of patients according to these treatments at the mCRPC stage. Patients and Methods This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. Results The present study included 180 patients for analyses. There was no difference in OS (log-rank test = 0.73), with a median follow-up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression-free survival than those who received docetaxel (log-rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39-0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression. Conclusion Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.

International audience; Introduction and Objectives Metastatic hormone-sensitive prostate cancer (mHSPC) accounts for 12% of prostate cancers diagnosed in Guadeloupe according to the Guadeloupean cancer registry. Most published studies have been conducted on the Caucasian population, whereas data concerning mHSPC in the Afro-Caribbean population are lacking. We aimed to describe the patient characteristics and estimate the progression-free survival of men with mHSPC in an Afro-Caribbean population according to the available treatment. Patients and Methods This was a monocentric retrospective study that consecutively included 133 men with mHSPC between January 1, 2015 and December 31, 2019 at the University Hospital of Guadeloupe. The primary endpoint was a description of the patients' characteristics with a description of complications at diagnosis. The secondary endpoint was progression-free survival. Kaplan-Meier survival and Cox proportional hazard analyses were performed. Results The median age at diagnosis was 71 years. The median prostate-specific antigen (PSA) was 147 ng/ml and 37% of patients presented with a disease-related complication at diagnosis. The survival analysis according to treatment showed median survival of 15 months for the androgen deprivation therapy (ADT) + chemotherapy group, 20 months for the ADT + new hormone therapy group, and 21.5 months for the ADT alone group, with no significant difference between the three therapeutic options (log-rank test: 0.27). In univariate analysis, none of the patient characteristics at diagnosis (i.e., age, PSA, bone lesions, visceral lesions) were significantly associated with the risk of progression, regardless of the treatment. Conclusion There was no significant difference in terms of progression-free survival between currently validated treatments administered in the first line, regardless of the tumor volume or risk group. Future studies with larger numbers of patients and involving molecular factors are required to confirm or invalidate these results and understand the evolution of prostate cancer in our population and thus better prevent complications related to the disease.

INTRODUCTION AND OBJECTIVE:Several risk classification tools are available to predict lymph node invasion (LNI) prior to radical prostatectomy while others predict biochemical recurrence (BCR) in p...

Introduction: Preoperative polymicrobial urine cultures are common, but the associated risk of nosocomial infection is currently unknown. We aimed to analyze the risk of postoperative infection in patients with preoperative polymicrobial urine cultures. Methods: This was a prospective cohort study conducted from November 2018 to October 2020. Polymicrobial urine cultures were defined by at least the presence of 3 bacteria without leukocyturia threshold on two consecutive samples in the month preceding the surgical procedure. Data on postoperative infections were collected during hospitalization until day 30. A postoperative infection was defined by the occurrence of clinical signs (fever, chills, and suppurated process on the surgical site) associated with the prescription of an antibiotic therapy. Results: Sixty-eight patients were included, and seven developed a postoperative infection with a microbe identified in blood or urine cultures. There was a significant association between leukocyturia ≥104 (p = 0.02) and the administration of intraoperative antibiotic prophylaxis (p < 0.001). In contrast, there was no significant association between postoperative infections for patients with polymicrobial preoperative urine cultures and having received or not an empirical antibiotic therapy. Conclusion: The rate of postoperative infection in patients with polymicrobial urine culture before urological procedure was 10.2%. Further studies are needed to assess the antibiotic prophylaxis to be used in this situation.

Background We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. Materials and methods Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. Results CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings. Conclusion We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.

International audience; Background: Mutations of the BRCA2 gene are the most frequent alterations found in germline DNA from men with prostate cancer (PrCa), but clinical parameters that could better orientate for BRCA2 mutation screening need to be established.Methods: Germline DNA from 325 PrCa patients (median age at diagnosis: 57 years old) was screened for BRCA2 mutation. The mutation frequency was compared between three subgroups: patients with an age at diagnosis at 55 years old and under (Group I); a personal or family history of breast, uterine or ovarian cancer (Group II); or a metastatic disease (Group III). Frequency of BRCA2 mutations was established for each combination of phenotypes, and compared between patients meeting or not the criteria for each subgroup using Fisher's exact test. Mutual information, direct effect, elasticity and contribution to the mutational status of each phenotype, taking into account overlap between subgroups, were also estimated using Bayesian algorithms.Results: The proportion of BRCA2 mutation was 5.9% in Group I, 10.9% in Group II and 6.9% in Group III. The frequency of BRCA2 mutation was significantly higher among patients of Group II (p = .006), and reached 15.6% among patients of this group who presented a metastatic disease. Mutual information, direct effect, elasticity and contribution to the mutational status were the highest for phenotype II. Fifteen (71.4%) of the 21 BRCA2 mutation carriers had an aggressive form of the disease. Four (19%) of them died from PrCa after a median follow-up duration of 64.5 months.Conclusions: Our results showed that a higher frequency of BRCA2 mutation carriers is observed, not only among PrCa patients with young onset or a metastatic disease, but also with a personal or a familial history of breast cancer.

We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. Genotypic data were obtained from PRACTICAL consortium for 6,253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with performance of PHS46+African. A calibration factor (CF) was formulated using estimated Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our dataset with 1000 Genomes, we identified statistically significant associations between continental and calibration groupings. In conclusion, we identified PCs within 8q24 SNP window that were strongly associated with performance of PHS46+African. Further research to improve clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry

In the version of this article originally published, the names of the equally contributing authors and jointly supervising authors were switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointly supervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in the HTML and PDF versions of the article.

International audience; Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

IntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46), showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify SNPs that might improve performance in this population.Material and MethodsAnonymized genotypic data were obtained from the PRACTICAL consortium for 6,253 men with African genetic ancestry. Ten iterations of a ten-fold cross-validation search were conducted, to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African were compared using the same cross-validated approach.ResultsThree SNPs (rs76229939, rs74421890, and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47 to 4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65 to 0.53).ConclusionsWe identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans and Asians. A strategy of building on established statistical models might benefit ancestral groups generally under-represented in genome-wide association studies.

International audience; Purpose - The Grade Group (GG) classification is recommended by guidelines as a reliable prognostic factor of prostate cancer. However, most studies have been performed on the Caucasian population. Our objective was to validate GG classification as a safe way to classify intermediate- and high-risk patients with African ancestry. Patients and methods - This was a retrospective study in an Afro-Caribbean population. A total of 1236 patients were included between 2000 and 2015. Patients were stratified according to (GG). Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analyses using the Cox model. Results - There was no significant difference at 5 and 10-year BCR-free survival between the intermediate- and high-risk groups, based on the D'Amico classification. There was a highly significant difference in BCR-free survival at 5 (p

Summary Background Prostate cancer is supposedly more aggressive among Afro-Caribbean men. There is a lack of data in this population for active surveillance. Published series are retrospective or have small samples and results are discordant. The objective was to determinate whether actual active surveillance modalities can be applied for Afro-Caribbean men by comparing their oncological outcomes with Caucasian men. Methods A total of 449 consecutive patients who underwent active surveillance for favorable-risk prostate cancer in two French University-Medical-Centers between 2005 and 2018: 261 in Guadeloupe, French West Indies, and 188 in Bordeaux, metropolitan France. Median follow-up was 56 months, (95% CI [32–81]) and 52 months (95% CI [30–75]), respectively (P = 0.07). Curative treatment was given in case of histological, biological, or imaging progression, or upon patient demand. Primary endpoints were treatment-free, overall and specific survival. Secondary outcomes were reasons of discontinuating active surveillance, histological poor prognosis factors after prostatectomy, CAPRA-S score, biochemical-recurrence-free after treatment and metastasis-free survival. Kaplan–Meier method was used. Results Median treatment free survival was 58.4 months (CI 95% [48.6–83.1]) for ACM and not reached at 120 months for CM (P = 0.002). Overall survival (P = 0.53), and specific survival (P = 0.21) were similar in the two groups. CM were likely to have poor prognosis factor on prostatecomy piece (57 vs 30%, P = 0.01). No difference for repartition of the CAPRA-S score (P = 0.86), biochemical-recurrence-free (P = 0.92) and metastasis-free (P = 0.44) survival. Conclusions Oncological outcomes for active surveillance of Afro-Caribbean and Caucasian men were similar in terms of mortality, recurrence and metastasis in our bicentric study, showing usability of current criteria for Afro-Caribbean. The higher rate of disease progression in the Afro-Caribbean population requires close monitoring. Level of evidence 3.

International audience; Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer. Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized prostate cancer. We analyzed the relationship between exposure to the estrogenic chlordecone, the anti-androgenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the non-dioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/anti-estrogenic properties and the risk of biochemical recurrence after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of biochemical recurrence, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% Confidence Interval 1.39-4.56 for the highest versus lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of prostate cancer treatment.

Resume Introduction Dans les pays developpes, l’incidence de la lithiase urinaire ne cesse d’augmenter avec le changement de regime alimentaire. La Guadeloupe est un Departement francais d’outre-mer ou se cotoient des habitudes alimentaires occidentales et une culture culinaire traditionnelle. L’objectif etait de decrire et d’analyser l’epidemiologie de lithiase urinaire en Guadeloupe. Materiel et methodes Nous avons realise une etude retrospective monocentrique incluant les patients hospitalises pour lithiase urinaire au CHU de Pointe-a-Pitre en 2015. Les caracteristiques des patients, les traitements utilises et les types de calculs etaient releves. Selon la composition minerale des calculs, des groupes etaient constitues. Resultats Au total, 165 patients ont ete inclus. Le sex-ratio etait de 1,61. L’indice de masse corporelle (IMC) median etait de 26,5 kg/m2. Les calculs etaient le plus frequemment composes d’oxalate de calcium (64,7 %). On retrouvait en seconde position les calculs mixtes (24,7 %). Les calculs d’acide urique representaient 3,5 % de l’echantillon. Les calculs oxalocalciques etaient en majorite monohydrates. Les calculs d’oxalate de calcium etaient significativement plus frequents chez l’hommes (80 % versus 47,5 %, p = 0,01) et chez les patients de plus de 50 ans (72,2 % versus 51,6 %, p = 0,04). Il n’y avait pas d’association entre le type de calcul et l’IMC. Conclusion Notre Departement d’outre-mer se rapproche donc de la metropole francaise en termes d’epidemiologie de la lithiase urinaire. Notre population se demarque par la proportion de femmes touchees par cette pathologie et par les proportions differentes de certains calculs. D’autres etudes sont necessaires pour etudier ces specificites. Niveau de preuve 4.

Resume Objectifs Recherche de facteurs predictifs de recidive biologique (RB) pouvant guider l’instauration d’un traitement adjuvant apres prostatectomie totale (PT) pour cancer avec marges chirurgicales positives (R+). Patients et methode Une cohorte retrospective de 1577 patients afro-caribeens operes d’une PT entre le 1er janvier 2000 et le 1er juillet 2013 a ete analysee. Dans cette cohorte, 406 patients avaient une marge chirurgicale positive, nous avons exclu 11 patients ayant beneficie d’un traitement adjuvant (radiotherapie, hormonotherapie, radio-hormonotherapie) et 2 patients pour lesquels l’analyse histologique de la piece operatoire etait en faveur d’un stade anatomo-pathologique pT4. Apres une analyse descriptive, nous avons utilise un modele de Cox afin de chercher des facteurs predictifs de survie sans recidive biologique (SSRB) puis, en fonction des variables significatives, nous avons separe notre population en six groupes : stade pT2 avec un score de Gleason ≤ 3 + 4 (groupe 1), stade pT2 avec un score de Gleason ≥ 4 + 3 (groupe 2), stade pT3a avec un score de Gleason ≤ 3 + 4 (groupe 3), stade pT3a avec un score de Gleason ≥ 4 + 3 (groupe 4), stade pT3b avec un score de Gleason ≤ 3 + 4 (groupe 5) et stade pT3b avec un score de Gleason ≥ 4 + 3 (groupe 6) et compare la SSRB en utilisant un log rank test. Resultats En analyse multivariee, les facteurs predictifs de SSRB apres PT R+ etaient le Gleason postoperatoire majoritaire (p Conclusion Un score de Gleason postoperatoire eleve (≥ 4 + 3) a une meilleure valeur predictive de recidive biologique que le stade pathologique pT2 ou pT3 chez les patients ayant ete traites d’un cancer de prostate par PT avec marges chirurgicales positives. Niveau de preuve 4.

Objectifs Plusieurs modeles existent pour predire le risque d’envahissement ganglionnaire pelvien mais aussi le risque de recidive biologique apres prostatectomie dans le cancer de prostate localise. Ces scores ont ete valides dans des populations en majorite caucasienne. Peu de donnees sont disponibles pour les populations d’ascendance africaine. L’objectif etait d’evaluer, d’une part, la performance des scores Memorial Sloan Kettering Cancer Centre (MSKCC) et Briganti dans la prediction de l’invasion ganglionnaire, et d’autre part, celle de la classification de D’Amico et des scores de CAPRA et CAPRA-S dans la prediction de la recidive biologique dans deux populations ethno-geographique differentes avec un acces aux soins similaires. Methodes Nous avons realise une etude retrospective bicentrique entre janvier 2000 et decembre 2017 incluant 3249 patients ayant justifie une prostatectomie radicale pour cancer de prostate localise (1830 Afro-antillais et 1419 Caucasiens). Les patients etaient classes par groupe de risque selon les classifications D’Amico et scores CAPRA et CAPRA-S. Parmi eux, 1065 patients justifiaient une lymphadenectomie pelvienne etendue (259 Afro-antillais et 806 Caucasiens). Les scores MSKCC et BRIGANTI 2012 etaient calcules a partir des donnees preoperatoires. La recidive biologique a ete definie par le dosage de 2 PSA consecutifs superieur a 0,2 ng/mL. La performance de ces scores etait testee par l’index C de discrimination de Harrell ou l’analyse de l’aire sous la courbe (AUC) des courbes ROC. Par ailleurs, des courbes de calibration etaient construites illustrant la relation entre les risques estimes et les proportions observees. Resultats L’âge median etait 64 ans (41–81). Le suivi median etait de 3,1 ans (0–22). Au total, 667 (21 %) patients ont presente une recidive biologique : 457 (25 %) Afro-antillais et 210 (15 %) Caucasiens. Le curage ganglionnaire etait positif chez 35 patients (3,3 %) : 15 sur 259 (5,8 %) dans le groupe Afro-antillais et 20 sur 806 (2,5 %) dans le groupe Caucasiens. Toutes les valeurs de C index etait plus faible chez les Afro-antillais par rapport a la cohorte caucasienne, respectivement ; D’Amico (0,62 vs 0,65), CAPRA (0,67 vs 0,68), CAPRA-S (0,69 vs 0,73). La performance de l’outil du MSKCC etait superieure dans le groupe Afro-antillais par rapport au groupe Caucasien (AUC respectivement a 0,69 et 0,65) (Tableau 1). Conclusion La performance des principaux scores predictifs d’envahissement ganglionnaire et de recidive biologique utilises de nos jours n’est pas equivalente au sein de deux populations francaises d’origine ethno-geographique differentes. Dans la population Afro-antillais, nos resultats suggerent d’utiliser le score MSKCC pour predire l’envahissement ganglionnaire et le score CAPRA-S pour predire la recidive biologique.

Objectifs La relation entre syndrome metabolique (SM) et cancer de la prostate (CaP) demeure controversee et tres peu d’etudes se sont adressees aux populations d’ascendance africaine. Nos objectifs etaient d’estimer la prevalence du SM chez des cas incidents de CaP d’ascendance afro-caribeenne et de mesurer le risque de recidive biologique associe au SM chez des patients traites par prostatectomie radicale (PR). Methodes Deux cent quatre-vingt-cinq patients ont ete inclus. Le SM a ete etabli par la presence d’au moins 3 des 5 criteres harmonises par l’American Heart Association (AHA) : obesite abdominale estimee par un tour de taille > 94 cm, triglycerides > 1,5 g/L, HDL-cholesterol 130 mmHg et/ou diastolique > 85 mmHg (ou traitement antihypertenseur), glycemie a jeun > 1,0 g/L (ou traitement anti-glycemique). L’insulinemie a jeun a permis de calculer l’indice d’insulinoresistance HOMA-IR. Deux cent dix-sept patients ont fait l’objet d’une PR. Le risque de recidive biologique a ete estime par le calcul du hazard ratio (HR) et de son intervalle de confiance (IC95 %). Resultats La prevalence du SM a ete estimee a 31,6 % (IC95 % : 25,9–37,2). Les criteres les plus frequemment associes au SM etaient l’hypertension arterielle (63,0 %) et l’obesite abdominale (56,7 %). En presence d’insulinoresistance (HOMA-IR > 2,5), la prevalence du SM etait de 14,8 % (IC95 % : 10,1–19,5). Ces prevalences ne differaient pas en fonction du score de Gleason (ISUP 3) sur biopsies au diagnostic. Le SM n’a pas ete retrouve associe au risque de recidive biologique, en absence ou en presence d’insulinoresistance (HR : 1,19 [IC95 % : 0,50–2,81] et 1,37 [IC95 % : 0,78–2,39] respectivement ; modeles ajustes a l’âge, marges chirurgicales, ISUP et stades pathologiques) apres un suivi median postoperatoire de 3,7 annees. Conclusion A notre connaissance, cette etude est la premiere qui estime la prevalence du SM selon les criteres harmonises de l’AHA dans une population de cas incidents de CaP d’ascendance afro-caribeenne. Dans cette population, le risque de recidive biologique apres traitement par PR n’est pas modifie par la presence d’un SM.

Background: Pheochromocytomas typically are diagnosed in the adrenal gland and from the sympathetic nervous system. Bladder pheochromocytoma is a rare location for this tumor. Case Presentation: We describe a 67-year-old Afro Caribbean woman referred to our hospital for an asymptomatic bladder tumor. Preliminary transurethral resection revealed bladder pheochromocytoma. After a comprehensive endocrine evaluation, we performed a robot-assisted laparoscopic partial cystectomy with ureteral reimplantation. Conclusion: We present a rare case of bladder pheochromocytoma treated effectively with minimally invasive techniques. When confronted with a solid bladder mass, apart from the more common urothelial malignancies, a differential diagnosis of bladder pheochromocytoma should also be considered.

INTRODUCTION AND OBJECTIVES:Prostate cancer (PCa) is supposedly more agressive among Afro-caribbean men (ACM). We compared oncologic results of active surveillance (AS) in ACM with Caucasian men (C...

INTRODUCTION Anthropometric data report that pelvic bone of African subjects are narrower and the pelvic cavity is deeper. The aim of the study was to evaluate the influence of pelvic dimensions (PD) on Positive surgical margins (PSM) rate in Afro-Caribbean population after robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS Preoperative pelvic MRI of all patients who have had RALP at the University Hospital Center of Guadeloupe between January 2013 and December 2015 was retrospectively analyzed. PD, including the Height of the upper edge of the prostate (HP), the Apical Depth (AD) and Ischial Spines Distance (ISD), and indexes (prostate volumetric index [ISD/VP], apical depth index [ISD/AD] and prostate depth index [ISD/(AD/HP)]) were compared according to the presence or absence of PSM with uni and multivariate analysis. RESULTS One hundred and seventy-eight patients were included in the study, of whom 60 (33.7%) presented PSM. In univariate analysis, significant differences between the presence or absence of PSM were observed on the AD (30.3±8.7mm versus 24.8±8.0mm, P

Background: There is an increasing body of evidence linking the exposure of an individual to pesticides such as organochlorine pesticides (OPCs) and an increased risk of developing diseases such as cancer. Exposure to OPCs has been suggested to increase the risk of developing hormone-dependant cancers such as prostate cancer (PCa). However, there is a relative paucity of information about the influence of exposure to these pesticides on the evolution of PCa, including risk of tumour development, progression to metastasis, and disease recurrence following therapy. Methods: We used several databases such as PubMed MEDLINE Database, Web of Science, and Scopus, in order to conduct a systematic review of the available epidemiological data implicating an association between exposure to OCPs and biochemical recurrence (BCR) of PCa. We searched all peer-reviewed articles published up to July 31st 2020. Pre-defined eligibility criteria for the inclusion of studies were that they be original studies, reviews, previous meta-analyses, or case–control or cohort studies. Results: Agent Orange is the most widely-studied OCP in the context of any possible causal role in the recurrence of PCa following radical prostatectomy, or in the progression to advanced disease. Only two studies didn’t demonstrate a significant association between exposure to OCPs and subsequent BCR following radical prostatectomy. Another study identified a significant association between exposure to Oxychlordane and PCB44 and progression to advanced PCa. Conclusion: This review confirmed a relative lack of high-quality evidence regarding this topic. However, the available evidence to date suggests the presence of a potential causal relationship between exposure to OPCs and PCa development and progression.

International audience; Background - Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness. Methods - From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA

Background Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours. Materials and methods Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned. Results We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 × 10−8, N = 746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours. Conclusion At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.

Objectifs De nombreuses etudes ont demontre l’apport voire la superiorite des biopsies ciblees (BC) par fusion elastique dans la detection des cancers de prostate cliniquement significatifs. Nous avons voulu etudier l’interet des biopsies ciblees par rapport aux biopsies standards (BS) et a l’association des deux dans notre population de patients ayant une suspicion de cancer de prostate. Methodes Il s’agit d’une etude retrospective monocentrique de 241 patients, aux antecedents biopsiques divers, ayant beneficie a la fois de biopsies standards et de biopsies ciblees sur des lesions identifiees par IRM multiparametrique de prostate (classification PIRADS version 2) avec un systeme de fusion elastique IRM-echographie entre fevrier 2017 et novembre 2018. Le critere de jugement principal etait le taux de cancers cliniquement significatifs (CS) entre les groupes BS, BC et la combinaison biopsies ciblees et standards. Les criteres de jugement secondaires etaient le taux de detection de cancer de prostate et la longueur de carotte maximale positive. Resultats La moyenne d’âge etait de 66,9 annees, le PSA et le volume prostatique moyens de 8,57 ng/mL et 59,6 cm3. Le taux de cancers CS etait significativement superieur dans le groupe biopsies ciblees + standards par rapport aux BS et aux BC, (85 [35 %] contre 71 [29,5 %] et contre 55 [22,8 %], p Tableau 1 , Tableau 2 ). Les taux de detection de cancer de prostate etaient de 66 % contre 59,3 % et 42,3 % dans les groupes combine, BS et BC respectivement, p Conclusion Cette etude de cohorte de patients Afro-caribeens ne retrouve pas de difference entre le groupe biopsies ciblees et le groupe biopsies standards pour la detection des cancers de prostate cliniquement significatifs. La combinaison biopsies ciblees et biopsies standards ameliore ce taux de detection.

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Few studies have investigated predictive risk factors of biochemical recurrence (BCR) after radical prostatectomy (RP) in other than Caucasian and Asian populations. We aimed to identify pre- and post-operative predictors of BCR after RP in an Afro-Caribbean population in Guadeloupe (French West Indies).The study included 964 patients who underwent RP for clinically localized prostate cancer between April 1, 2000 and December 31, 2010 in the University Hospital of Guadeloupe. The hazard ratio (HR) and corresponding 95% confidence interval (CI) for single variable associations with BCR were calculated using the Cox proportional hazards regression. Multiple variable analyses for association with BCR were performed, including all variables that reached statistical significance (P value0.05) in univariate analysis. A backward selection model was then applied with a P value ≥0.1 for retention in the final model. Sensitivity analysis was performed and restricted to patients with known values for all variables (complete case analysis).With a median follow-up of 4.8 years, the BCR rate was 26.7%. In multivariable analysis, predictors of BCR before surgery were diabetes mellitus type 2 (DT2) (HR: 1.37, 95% CI: 1.02-1.85; P=0.038), pre-operative PSA7.5ng/ml (1.49, 1.15-1.92; P=0.002), clinical stage T2 (1.55, 1.21-1.98; P=0.0006), Gleason score7 or 4+3 (2.12, 1.54-2.91; P0.0001), and percentage of length of biopsy positive scores (1.66, 1.24-2.20; P=0.0006). Predictors of BCR after surgery were DT2 (HR: 1.37, 95% CI: 1.01-1.85; P=0.045), pre-operative PSA7.5ng/ml (1.37, 1.06-1.79; P=0.018), pathological Gleason score7 or 4+3 (2.36, 1.74-3.19; P0.0001), pathological stage pT3b (1.68, 1.15-2.45; P=0.007), positive surgical margins (1.72, 1.32-2.45; P=0.0001), and perioperative blood loss2000ml (3.74, 1.37-10.2; P=0.01). The results were virtually the same by sensitivity analysis (complete cases), except for DT2, which was associated with BCR with borderline statistical significance in the pre-operative model and not retained in the post-operative model.Afro-Caribbean populations in French West Indies share the same major clinical and pathological risk factors of BCR after RP identified in other ethnic groups. Perioperative blood loss appears to be an additional and independent predictive factor of BCR.4.