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Background and Objective: Prostate cancer (PCa) was the leading incident cancer and 3rd leading cause of cancer death in men in France in 2015 with inter-regional disparities. The objectives were to describe PCa incidence and mortality in France and by region, using real life data from the National Health Data System and to identify the factors associated with all-cause or PCa-specific mortality., Methods: Men aged ≥ 18years hospitalized and/or on long-term care for PCa (ICD-10 code C61) in France between 2010 and 2021 were included. An incident case was defined by the absence of any cancer in the five years preceding the first coding. Incidence and mortality estimates were age-standardized: France 2018f standardized rates (FSR), all-cause mortality (SMR) and PCa-specific mortality (SMRspe). Factors associated with death were identified using cause-specific Cox models., Results: The mean annual incidence was 47,081cases/year (FSR:179.6/100,000men), increasing over the period except 2020. All-cause mortality was 20,259 deaths/year (77.3/100,000men), and PCa-specific mortality was 7,265 deaths/year (27.7/100,000men). A PCa-specific mortality excess was found in Centre-Val-de-Loire (SMRspe = 1.21), Bretagne (1.18), Hauts-de-France (1.17) Normandie (1.15). After adjustment, significant PCa mortality excess was observed in Bretagne (HR = 1,29; 95% IC[1.09-1.46]) and Hauts-de-France (HR = 1.19[1.03-1.34]). The other factors associated with death were an age ≥ 60years, an increasing comorbidity index, metastatic disease at onset (major weight in specific mortality with hazard ratio HR = 16.1[15.2-17.0]), precariousness, affiliation to the agricultural scheme, and the COVID period in all-cause mortality., Conclusion: This study updated incidence and mortality data in France. It showed differences in mortality between regions in France. The adjustment moderates regional findings based on raw mortality data., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Periprostatic fat has a metabolic activity on the prostate via cytokines that act paracrine on several signaling pathways including tumorigenesis. We investigated whether there was an association between preprostatic fat abundance and prostate cancer (PCa) aggressiveness., Materials and Methods: We performed a retrospective study including patients who underwent radical prostatectomy in our center from the prospective RESCAP database. Preoperative MRIs were re-read and different measurements of preprostatic fat (PPF) were performed. The maximum thickness (PPFmax) and the minimum thickness (PPFmin) were measured on a median T2 sagittal section. The total volume of preprostatic fat (PPFV) and volume normalized by prostate volume (NPPFV) were calculated semi-automatically by segmentation on continuous axial sections of 3mm. The association of these parameters with the aggressiveness criteria of PCa (ISUP 3-5 on biopsies and on operative specimen, intermediate or high-risk disease according to D'AMICO, PSA>10, upgrading risk at radical prostatectomy) was measured as well as the association between normal, overweight, and obese BMI classes and the aggressiveness criteria used., Results: One hundred and twenty-one men were included in this study. In both the univariate analysis and the multivariate analysis, none of the preprostatic fat measurements (PPFmax, PPFmin, PPFV and NPPFV) were associated with PCa aggressiveness criteria. There was also no association between BMI class and tumor aggressiveness., Conclusion: In this study, there is no association between the abundance of preprostatic fat and PCa aggressiveness according to the periprostatic fat measurements achieved., Level of Evidence: III., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Prostate biopsy is sometimes complicated by infection which can lead to death. The risk factors remain controversial, notably the urine bacterial culture carried out before a prostate biopsy. The increase in resistance induces an increase in the number of complications and the need to define new antibiotic prophylaxis strategies. The urine bacterial culture remains widely discussed in cases with post-prostate biopsy infections and urologists or experts await clear recommendations on this subject. The Infectiology Committee of the French Association of Urology has therefore set up a literature analysis work in order to reach a consensus within the committee., Method: A literature search was performed on Pubmed and Medline. We selected randomized studies or meta-analyzes using the keywords "prostate biopsy" and "infection" or "infectious complications". All abstracts and articles have been analyzed. The summary of the analysis was reviewed by all the members of the committee proposing the most consensual recommendation possible., Results: The literature on the subject remains poor, but no evidence of a link between prebiopsy bacteriuria and post-biopsy infection has been demonstrated., Conclusions: Apart from a clinical situation which could evoke a male urinary tract infection, and moreover having to prefer the postponement of biopsies, it is not recommended to perform a routine urine culture before endo-rectal prostate biopsies (expert opinion)., (Copyright © 2020. Published by Elsevier Masson SAS.)

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

In prostate cancer research, there is a lack of valuable preclinical models. Tumor cell heterogeneity and sensitivity to microenvironment signals, such as hypoxia or extracellular calcium concentration, are difficult to reproduce. Here, we developed and characterized an ex vivo tissue culture model preserving these properties. Prostate tissue slices from 26 patients were maintained ex vivo under optimized culture conditions. The expression of markers associated with proliferation, androgen-receptor signaling, and hypoxia was assessed by immunostaining. A macroscope was used to achieve real-time calcium fluorescence optical imaging. Tissue morphology was maintained successfully without necrosis for 5 days. Compared with native tumors and tissue cultured with androgens, androgen deprivation in the medium led to decreased expression of both androgen receptor and its target gene products, prostate specific antigen (PSA) and ETS-related gene (ERG). Ex vivo cultured slices also were sensitive to hypoxia because carbonic anhydrase IX and zinc finger E-box binding homeobox 1 (Zeb1) protein levels increased in 1% oxygen. Exposure of slices to supraphysiological extracellular Ca 2+ concentration induced a robust and rapid Ca 2+ entry, with a greater response in tumor compared with nontumor tissue. This ex vivo model reproduces the morphologic and functional characteristics of human prostate cancer, including sensitivity to androgen deprivation and induced response to hypoxia and extracellular Ca 2+ . It therefore could become an attractive tool for drug response prediction studies., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP)., Methods: All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05., Results: Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively)., Conclusion: MetS was an independent predictive factor for higher ISUP group and positive margins at RP. Low HDL-cholesterol alone, and having 4 and more MetS components were also associated with higher risk of adverse pathological features., (Copyright © 2018. Published by Elsevier Inc.)

The process of epithelial-to-mesenchymal transition (EMT) contributes to cancer progression, with activation of transcription factors leading to loss of epithelial characteristics and acquirement of mesenchymal properties. We analyzed in human prostate cancer (PCa) the expression of EMT markers at the different stages of PCa natural history, and evaluated its clinical significance. The expression of the key EMT transcription factor Zeb1, together with E-cadherin, vimentin, and N-cadherin, was evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate (n = 58), clinically localized cancer (CLC) (n = 242), castration-resistant PCa (CRPC) (n = 48), and metastases (n = 43). Zeb 1 expression was not found in normal tissues, and significantly increased with disease progression from pT2 (20% of cases) to pT3 tumors (34%), and then from CLC to metastases and CRPC (62% and 92%). The expression of EMT target genes was more fluctuant according to disease stages, although in CLC N-cadherin was closely associated with Zeb1 staining. In CLC, after adjusting for classical prognostic markers, only vimentin expression was significantly predictive of shorter recurrence-free survival. In CRPC, preserved E-cadherin staining was associated with longer overall survival, and Zeb1 expression in metastases was predictive of decreased survival. Although Zeb1 expression increased according to the different steps of PCa progression, the expression of its target genes does not seem to follow the same kinetics. However, the potential clinical interest of these EMT markers at several stages of the disease is strongly suggested by their predictive value on both recurrence-free and overall survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In vitro studies in prostate cancer (PCa) cell lines have suggested a key and complex role of the store-operated channels (SOCs) in major cancer hallmarks, including proliferation, apoptosis, and migration. In the present study, we investigated in vivo the expression of the SOC components transient receptor potential canonical (TRPC) 1, TRPC4, Orai1, and stromal interaction molecule 1 (STIM1), during all stages of PCa progression, and evaluated their prognostic impact in clinically localized cancer (CLC). The expressions of TRPC1, TRPC4, Orai1, STIM1, and the androgen receptor and the proliferation marker Ki-67 were evaluated by immunohistochemistry on tissue microarrays containing samples of normal prostate tissues (n=91), prostatic intraepithelial neoplasia (n=61), CLC surgically treated (n=238), and castration-resistant prostate cancer (CRPC; n=45). All markers significantly increased in CLC compared with normal tissues and (for Orai1 and STIM1) in advanced pT3 tumors compared with pT2. In contrast, their expression decreased in CRPC, particularly for Orai1. In CLC, staining for TRPC1, Orai1 and STIM1 correlated with androgen receptor expression, and TRPC1 status was associated with lower proliferation and longer recurrence-free survival, after adjusting for classical prognostic markers. Although increased SOC expression during PCa progression supports a role in cancer cell migration, the inverse association between TRPC1 and biochemical relapse suggests a protective effect in CLC. Moreover, the dramatic down-regulation of Orai1 in CRPC supports its role in apoptosis at this stage of the disease. These results call for caution when considering SOCs as potential therapeutic targets for PCa., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months., Methods: Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders., Results: Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients., Conclusion: Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.

Aim: Laparoscopic pelvic lymphadenectomy in localized prostatic cancer is performed since the 1990s, lessens the postoperative complications and respects carcinologic's principles (No. lymph nodes removed and lymph nodes metastasis). In order to verify that these objectives are achieved, we compared our results of pelvic lymphadenectomy by laparotomy and by laparoscopy for the past 12 years., Patients and Methods: Between January 1997 and June 2008, 36 (23.8%) patients underwent open pelvic lymphadenectomy and 76.16% (115 cases) laparoscopic pelvic lymphadenectomy. We did a retrospective and comparative analysis of data including the preoperative characteristics, per- and postoperative complication as well pathologic results., Results: Preoperative data were comparable between both groups. The comparison of the peroperative data showed an increased bleeding volume in the open group (105.6±420.9mL; 12.1±96.1mL: P=0.001) and longer operative time in the laparoscopic group (103.7±83.9min; 132.8±40.9min: P=0.006). Postoperative complications were similar. Pathologic results showed a significantly more important number of lymph nodes removed in the open group (7.2±3.5; 5.7±3.2: P=0.022), but the positive rate similar in both groups (13.9%; 22.6%: P=0.258). In order to remove "the learning curve effect", we compared 36 open pelvic lymphadenectomy to the last 36 laparoscopic pelvic lymphadenectomy. In the laparoscopic group the patients showed an upper Gleason score (6.3±1.1; 7±1: P=0.005); but there was no difference for the operative time, number of lymph nodes removed and the complications rates., Conclusions: After training, laparoscopic pelvic lymphadenectomy was similar to open pelvic lymphadenectomy., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To determine if obesity is associated with prolonged surgery or more complications during and after surgery in patients undergoing robot-assisted laparoscopic prostatectomy (RALP)., Patients and Methods: Between December 2003 and September 2005 data were collected prospectively for all patients undergoing RALP. Obesity was defined as a body mass index of > or = 30 kg/m2. The duration of surgery was recorded, determining the duration of steps, including overall, robotic assistance, and vesico-urethral anastomosis. In all, 285 patients had RALP by one of two surgeons; 236 were classified as not obese and 49 as obese., Results: The characteristics of the two groups were similar before and after RALP (mean age 60.7 vs 60.3 years, prostate-specific antigen level 7.9 vs 7.9 ng/mL, prostate weight 47.3 vs 45.3 g, length of stay 3.2 vs 3.5 days, and indwelling catheterization 8.3 vs 7.9 days). The mean duration of surgical steps was less for the non-obese than the obese group, with urethral dissection requiring 16 vs 19.3 min (P < 0.05), anastomotic time 30 vs 36 min (P < 0.01), and port closure 11 vs 14.5 min (P < 0.001), but the total duration of surgery, at 190 vs 205 min, was not significantly different (P = 0.07). In the non-obese group there were seven (3%) prolonged drain tube leaks, vs four (8%) in the obese group (P = 0.08)., Conclusions: Obesity was associated with longer anastomotic times, but the overall duration was similar. Overall complication rates were not significantly different. The continuing follow-up will determine if obesity predisposes patients to greater long-term morbidity after RALP.