Search

Objective: The aim of the Oncology Committee of the French Urology Association is to propose updated recommendations for the diagnosis and management of localized prostate cancer (PCa)., Methods: A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the elements of diagnosis and therapeutic management of localized PCa, evaluating references with their level of evidence., Results: The recommendations set out the genetics, epidemiology and diagnostic methods of PCa, as well as the concepts of screening and early detection. MRI, the reference imaging test for localized cancer, is recommended before prostate biopsies are performed. Molecular imaging is an option for disease staging. Performing biopsies via the transperineal route reduces the risk of infection. Active surveillance is the standard treatment for tumours with a low risk of progression. Therapeutic methods are described in detail, and recommended according to the clinical situation., Conclusion: This update of French recommendations should help to improve the management of localized PCa., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Radical prostatectomy (RP) can be performed using an open (ORP), laparoscopic (LRP) or robotic (RARP) approach. Most studies, even in experienced centers, have not provided solid evidence demonstrating better outcomes when using the robotic approach. In addition, one of the remaining concerns about RARP is its cost effectiveness, leading to no reimbursement for this surgical technique in some countries and thus health care inequality. We used data from a French national registry to improve knowledge of RP outcomes in a real-world scenario in order to guide and inform health care decision-makers. A total of 21 213 RP procedures were performed in 645 French centers in 2021 (ORP 20%, LRP 25%, and RARP 55% of cases). ORP was associated with longer hospital stay (p < 0.001), higher rates of postoperative complications (p < 0.001), fewer days out of hospital within 90 d of surgery (81.7 vs 83.6 vs 84.9 d for ORP vs LRP vs RARP; p < 0.00), and higher hospitalization costs (€2424 vs €1789 vs €1302). RARP is an optimal and cost-effective approach, with several advantages over ORP. Our data can be used by health care decision-makers to facilitate access to and reimbursement for the robotic approach for RP indications. PATIENT SUMMARY: For men with prostate cancer for whom surgery is recommended, surgeons can remove the prostate using open surgery or a keyhole approach with or without robot assistance. Open surgery has higher costs, more complications, and longer hospital stays., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Prostate cancer (PCa) is a public health issue. The diagnostic strategy for PCa is well codified and assessed by digital rectal examination, PSA testing and multiparametric MRI, which may or may not lead to prostate biopsies. The formal benefit of organized PCa screening, studied more than 10 years ago at an international scale and for all incomers, is not demonstrated. However, diagnostic and therapeutic modalities have evolved since the pivotal studies. The contribution of MRI and targeted biopsies, the widespread use of active surveillance for unsignificant PCa, the improvement of surgical techniques and radiotherapy… have allowed a better selection of patients and strengthened the interest for an individualized approach, reducing the risk of overtreatment. Aiming to enhance coverage and access to screening for the population, the European Commission recently promoted the evaluation of an organized PCa screening strategy, including MRI. The lack of screening programs has become detrimental to the population and must shift towards an early detection policy adapted to the risk of each individual., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa)., Methods: A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022., Results: Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3-5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease., Conclusion: The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet., Methods: We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB., Results: Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I 2  = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I 2  = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis., Conclusion: Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy., Methods: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes., Results: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM., Conclusions: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prostate surgery mainly addresses the treatment of the two most common pathologies of the prostate: benign prostatic hypertrophy (BPH), symptomatic or complicated, and prostate cancer (PCa). The objective of this manuscript was to present after review of the literature the main intraoperative and postoperative surgical complications associated with radical prostatectomy and surgery of the BPH whatever the surgical approach. The incidence and type of these complications may vary depending on the patient's comorbidities and the type of surgery. Regarding radical prostatectomy, the main complications are hemorrhagic, digestive and urinary. During or after surgery of BPH, hemorrhagic and urinary complications dominate. The management of these complications relies on general principles based on a low level of evidence, but usually associate a structured diagnostic pathway and an appropriate treatment decision., (Copyright © 2022. Published by Elsevier Masson SAS.)

Adapted physical activity (APA) appears to be essential for supportive care in oncology. It helps to reduce different side effects inherent to treatment and disease (e.g., fatigue, sarcopenia, balance problems) and could have an impact on patients' survival. However, it is not systematically implemented in daily practice and still too few patients reach the recommendations of physical activity. New tools, such as digital and connected ones, are now developed to overcome barriers to the implementation and daily practice of physical activity (e.g., distance between home and hospital). The aim of this article was to provide an overview of different connected tools that offer exercise training and monitoring programmes in prostate cancer., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: The risk of recurrence is increased in localized high-risk prostate cancer (PCa). The implementation of an appropriate diagnostic and therapeutic strategy is essential. The objective of this update by the Prostate Committee of the French Association of Urology was to report the most recent data in the management of localized high-risk PCa., Material and Methods: This update is based on the data available in the literature on localized high-risk PCa. A PubMed search and narrative review of the recent data were performed in March 2022., Results: Compared with conventional imaging, PET-PSMA is more effective for the diagnosis of lymph nodes and distant metastases. Two recent randomized clinical trials have failed to prove the oncologic benefit of extended pelvic lymph node dissection during radical prostatectomy (RP). Postoperatively, early salvage radiotherapy is the standard of care, with adjuvant radiotherapy becoming an option in case of unfavorable pathological criteria (ISUP 4-5, pT3±positive margins) in young patients. Although promising, perioperative systemic therapies (chemotherapy, second-generation hormonotherapy) cannot be recommended at this time when the patient is treated by RP. Regarding radiotherapy, prophylactic lymph node irradiation during prostatic irradiation was associated with improved biochemical and metastasis-free survival in a recent randomized trial but it is still controversial. Since the publication of the results of the STAMPEDE trial, the addition of abiraterone acetate to radiation-hormone therapy should be considered the new standard of care for patients with localized (very) high-risk PCa, according to the inclusion criteria of the study., Conclusion: The most recent data of the literature regarding the management of high-risk localized PCa redefine the diagnostic performance of molecular imaging, the timing of postoperative radiotherapy, the oncologic benefit of pelvic lymph node treatment, and the intensification of systemic therapies., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Hospital volume is considered to be a quality measure for outcomes after major oncological surgery. However, countrywide data are lacking for radical prostatectomy (RP)., Objective: To assess the impact of hospital volume on postoperative outcomes after RP performed using an open (ORP) versus a minimally invasive surgery (MIS, including pure and robot-assisted RP) approach., Design, Setting, and Participants: Data for patients undergoing RP in France from 2014 to 2019 were extracted from the central database of the national health care system., Outcome Measurements and Statistical Analysis: Primary endpoints were length of hospital stay (LOS), complications (measured as severity index [SI] scores), and hospital readmission rates at 30 and 90 d., Results and Limitations: The median annual hospital volume was 19 RPs (interquartile range 1-40) in the overall cohort. MIS was associated with better outcomes than ORP. Greater hospital volume was correlated with shorter LOS (p < 0.001), high SI scores (SI3: p < 0.001; SI4: p < 0.001), and 30-d (p < 0.001) and 90-d readmission rates (p < 0.001). Incidence rates for SI3 and SI4 scores, and 30-d and 90-d readmission were 12.8 %, 5.8 %, 29.8 %, and 35.4 % in very low-volume centres (<10 annual cases) compared with 8.1 %, 1.9 %, 18.1 %, and 23.9 %, respectively, in other centres (all p < 0.001). Hospital volume was an independent risk factor for all outcomes after taking into account age, lymph node dissection, year of surgery, and surgical approach (ORP vs MIS). The main limitation is the lack of post-RP oncological and functional data., Conclusions: This nationwide analysis of RP procedures shows a significant correlation between hospital volume and postoperative outcomes irrespective of the surgical approach. Very low case volume (<10 annual procedures per centre) is associated with the highest risk of complications, readmission, and prolonged LOS. Greater hospital volume is directly correlated with shorter LOS even beyond this threshold., Patient Summary: In this study we analysed the French nationwide database for removal of the prostate for prostate cancer. We found that the number of these cases that a hospital carries out per year was associated with outcomes after surgery, with better outcomes for higher annual case numbers., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Clinical image data analysis is an active area of research. Integrating such data in a Clinical Data Warehouse (CDW) implies to unlock the PACS and RIS and to address interoperability and semantics issues. Based on specific functional and technical requirements, our goal was to propose a web service (I4DW) that allows users to query and access pixel data from a CDW by fully integrating and indexing imaging metadata. Here, we present the technical implementation of this workflow as well as the evaluation we carried out using a prostate cancer cohort use case. The query mechanism relies on a Dicom metadata hierarchy dynamically generated during the ETL Process. We evaluated the Dicom data transfer performance of I4DW, and found mean retrieval times of 5.94 seconds and 0.9 seconds to retrieve a complete DICOM series from the PACS and all metadata of a series. We could retrieve all patients and imaging tests of the prostate cancer cohort with a precision of 0.95 and a recall of 1. By leveraging the CMOVE method, our approach based on the Dicom protocol is scalable and domain-neutral. Future improvement will focus on performance optimization and de identification.

Patients treated by radical prostatectomy (RP) for localized prostate cancer (PCa) may experience biochemical recurrence (BCR) in approximately 30% of cases. Recently, advances in imaging modalities and in particular Positron-Emission Tomography with computed tomography (PET/CT) imaging allow for better detection and characterization of lesions outside the prostatic bed at recurrence. Thus, treatment at BCR can be significantly improved by a tailored strategy based on new generation imaging. A more precise and accurate staging of the disease at recurrence paves the way to more appropriate treatment, potentially translating into better survival outcomes of these patients. This review therefore highlights the interest of PET/CT at the time of BCR, its superiority over standard imaging in terms of staging, and its impact on guiding the different therapeutic possibilities depending on the site, number, and volumes of recurrence. Indeed, we will discuss below about different strategies and their indications: salvage radiotherapy of the prostate bed, systemic therapies, stereotactic body radiotherapy and others therapeutical strategies. The various innovative approaches based on PET/CT implementation are partly underway within protocol trials to prove their benefits on clinically meaningful endpoints. © 2022 Elsevier Masson SAS. All rights reserved., Competing Interests: Disclosure of interest A. Ruffion, M. Lasserre, P. Sargos, G. Fiard, E. Barret and J.-B. Beauval have no competing interest to declare regarding this article. C. Dariane declares competing interest by participating in clinical trials (as co-investigator, non-principal experimenter, or collaborator) for Janssen and Bayer; receiving compensation for advisory consultancies from Janssen, Bayer, Astellas; being invited to conference as a speaker by Janssen and being invited to congresses with paid expenses by Bayer. M. Rouprêt de declares competing interest by participating in clinical trials (as principal investigator, coordinator, or principal experimenter) for Roche, Janssen, AstraZeneca and by receiving compensation for advisory consultancies from Astellas, Ferring, Roche, Janssen, AstraZeneca, Bayer and Ipsen. G. Ploussard declares competing interest by participating in clinical trials (as principal investigator, coordinator, or principal experimenter) for Ferring, Janssen, Ipsen, AstraZeneca, Pfizer, Bayer; by participating in clinical trials (as co-investigator, non-principal experimenter, or collaborator) for Ferring, Janssen, Ipsen, AstraZeneca, Pfizer, Bayer; receiving compensation for advisory consultancies from Ferring, Janssen, Ipsen, AstraZeneca, Pfizer, Bayer, Astellas, Intuitive, Thermo Fisher; being invited to conference as a speaker by Ferring, Janssen, Ipsen, AstraZeneca, Pfizer, Bayer, Astellas, Intuitive, Thermo Fisher. M. Gauthé declares competing interest by participating in clinical trials (as principal investigator, coordinator, or principal experimenter) for Curium Pharma, ABX Biochemical compounds, Endocyte/Novartis; receiving compensation for advisory consultancies from Curium Pharma; being invited to conference as a speaker by Novartis, Astellas; being invited to congresses with paid expenses by Curium Pharma, ABX Biochemical compounds, Endocyte/Novartis. G. Fromont declares competing interest by being invited as a speaker to conference by AstraZeneca and Astellas. R. Mathieu declares competing interest by receiving compensation for advisory consultancies from Bayer, Astellas, Janssen and by being invited as a speaker by Bayer, Astellas and Janssen. G. Roubaud declares competing interest by participating in clinical trials (as principal investigator, coordinator, or principal experimenter) for Bayer, Janssen, AAA, Novartis, Astellas, MSD, AstraZeneca; by receiving compensation for advisory consultancies from Merck and AstraZeneca; by being invited as a speaker to conferences by Jansses, AAA, Novartis, Astellas, AstraZeneca, Merck and by being invited to congresses with paid expenses by Astellas, Janssen and AstraZeneca. L. Brureau, G. Créhange, R. Renard-Penna did not disclose their conflict of interest., (Copyright © 2022 Elsevier Masson SAS. Tous droits réservés.)

Purpose: This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP)., Methods: We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term (<6 months) or long-term (≥6 months) neoadjuvant ADT before RP., Results: Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93-1.51, p  = 0.17), metastasis (OR 0.73, 95% CI, 0.45-1.19, p  = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43-1.21, p  = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39-0.80, p  = 0.001, and OR 1.48, 95% CI 1.10-1.99, p  = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00-3.93)., Conclusion: Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.

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.)

The safety profile of androgen deprivation therapy (ADT) is well known, and cardiovascular and osteoporosis risk factors should be assessed before ADT initiation. In order to examine whether the French Committee of Urologic Oncology Prostate Cancer (PCa) Guidelines were properly followed by clinicians, including urologists, oncologists and radiotherapists, we used a nationwide comprehensive cohort of prostate cancer patients, who were new ADT users in 2011 and were followed-up to 2013. Reimbursements for biological examinations and prescribers were identified, as well as PCa specialist consultations at drug initiation. Our results in this French cohort showed that the proportions of patients resorting to specialized care between one year and 3 months before ADT initiation and in the 6 months following was around 40% for fasting glucose and 30% for lipid assessments. Bone densitometry was performed in approximately 1% of patients. In the 12 months after ADT initiation, 75% of the patients were seen by a urologist and about 47% by an oncologist or a radiotherapist. Overall, there is still room for improvement in terms of ADT monitoring by clinicians and in the information provided to general practitioners and patients regarding the expected adverse effects of this treatment.

Background: Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri-prostatic adipose tissue (PPAT) has been shown to differ according to the ethno-geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African-Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues., Methods: The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African-Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3-5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays., Results: The amount of cholesterol esters was lower in PPAT from African-Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African-Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP-2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP-2 expression was strongly associated with that of Zeb1, a key player in the epithelial-to-mesenchymal transition (EMT) process., Conclusion: These results suggest that cholesterol metabolism differs according to the ethno-geographic origin, in both PPAT and cancer tissues. In African-Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population., (© 2021 Wiley Periodicals LLC.)

Objective: Purposes of this work were i) to develop an in silico model of tumor response to radiotherapy, ii) to perform an exhaustive sensitivity analysis in order to iii) propose a simplified version and iv) to predict biochemical recurrence with both the comprehensive and the reduced model., Methods: A multiscale computational model of tumor response to radiotherapy was developed. It integrated the following radiobiological mechanisms: oxygenation, including hypoxic death; division of tumor cells; VEGF diffusion driving angiogenesis; division of healthy cells and oxygen-dependent response to irradiation, considering, cycle arrest and mitotic catastrophe. A thorough sensitivity analysis using the Morris screening method was performed on 21 prostate computational tissues. Tumor control probability (TCP) curves of the comprehensive model and 15 reduced versions were compared. Logistic regression was performed to predict biochemical recurrence after radiotherapy on 76 localized prostate cancer patients using an output of the comprehensive and the reduced models., Results: No significant difference was found between the TCP curves of the comprehensive and a simplified version which only considered oxygenation, division of tumor cells and their response to irradiation. Biochemical recurrence predictions using the comprehensive and the reduced models improved those made from pre-treatment imaging parameters (AUC = 0.81 ± 0.02 and 0.82 ± 0.02 vs. 0.75 ± 0.03, respectively)., Conclusion: A reduced model of tumor response to radiotherapy able to predict biochemical recurrence in prostate cancer was obtained., Significance: This reduced model may be used in the future to optimize personalized fractionation schedules.

Objective: The aim of the study was to determine the trend of first blood prostate-specific antigen (PSA) test prescription in France between 2011 and 2017, based on the assumption that prostate cancer (PCa) screening is expected to decline over the years., Method: Using a representative sample of the French population from the French Health Insurance database, we identified 50-52-year-old men without PCa and without any blood PSA test in the five years before 2011, 2014 and 2017 (January 1-December 31 of each year). For each of these three years, the primary outcome was the first reimbursement of a blood PSA test. We used a logistic regression model with first blood PSA test as the outcome and year as the main explanatory variable. As secondary objectives, we also identified the prescriber's specialty, the urological consultation frequency, and the number of prostate biopsies in the year after the first blood PSA test reimbursement (only for 2011 and 2014)., Results: In 2011, 2014 and 2017, 5 275, 5 792 and 5 887 50-52-year-old men, respectively, were included. The percentage of patients with a first blood PSA test prescription decreased linearly from 2011 to 2017: 15.7% in 2011, 13.2% in 2014, and 12.4% in 2017 ( p  < .001). Blood PSA testing was mainly prescribed by general practitioners (>95%). The median interval between PSA tests was 13 months in 2011 and 14 months in 2014. Fewer than 10% of men had ≥1 consultation with an urologist during the year after the first blood PSA test. After the first blood PSA test, eight prostate biopsies were performed in 2011 and two in 2014., Conclusion: Our results suggest that in France, PCa screening is a primary care issue. Although PCa screening remains controversial and confusion exists about the best practice, our study showed a linear decrease of blood PSA test prescriptions for 50-52-year-old men between 2011 and 2017, although the reason for screening was unknown. As clinical information was not available, additional evidence is needed to determine the real impact of this decrease on the cancer-specific and overall mortality.

Purpose of Review: Radiogenomics, fusion between radiomics and genomics, represents a new field of research to improve cancer comprehension and evaluation. In this review, we give an overview of radiogenomics and its most recent and relevant applications in prostate cancer management., Recent Findings: Literature about radiogenomics in prostate cancer emerged last 5 years but remains scarce. Radiogenomics in prostate cancer mainly rely on MRI-based features. Several imaging biomarkers, mostly based on the identification of radiomic features from deep learning studies, have been studied for the prediction of genomic profiles, such as PTEN Decipher Oncotype DX or Prolaris expression. However, despite promising results, several limitations still preclude any integration of radiogenomics in daily practice., Summary: In the future, the emergence of artificial intelligence in urology, with an increasing use of radiomics and genomics data, may enable radiogenomics to assume a growing role in the evaluation of prostate cancer, with a noninvasive and personal approach in the field of personalized medicine. Further efforts are necessary for integration of this promising approach in prostate cancer decision-making., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To access the feasibility of palliative cystoprostatectomy/pelvic exenteration in patients with bladder/rectal invasion due to prostate cancer (PC)., Patients and Methods: Twenty-five men with cT4 PC were retrospectively identified in the institutional databases of six tertiary referral centers in the last decade. Local invasion was documented by CT or MRI scans and was confirmed by urethrocystoscopy. Oncological therapies, local symptoms, previous local treatments, time from diagnosis to intervention and type of surgical procedure were recorded. Patients were divided into groups: ADT group (12 pts) and 13 pts without any history of previous local/systemic treatments for PCa (nonADT groups). Perioperative complications were classified using the Clavien-Dindo system. Overall survival (OS) was defined as the time from surgery to death from any cause. A Cox regression analysis, stratified for ISUP score and previous hormonal treatment (ADT) was also performed for survival analysis., Results: Ileal conduit was the main urinary diversion in both cohorts. For the entire cohort, complication rate was 44%. No significant differences regarding perioperative complications and complication severity between both subgroups were observed (p = 0.2). Median follow-up was 15 months (range 3-41) for the entire cohort with a median survival of 15 months (95% CI 10.1-19.9). In Cox regression analysis stratified for ISUP score, no statistically significant differences in OS in patients with and without previous ADT before cystectomy or exenteration were observed (HR 3.26, 95% CI 0.62-17.23, p = 0.164)., Conclusion: Palliative cystoprostatectomy and pelvic exenteration represent viable treatment options associated with acceptable morbidity and good short-term survival outcome., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine whether small cell neuroendocrine prostate cancers (NEPCa) emerging after anti-androgen treatments are different from the rarest cases diagnosed de novo, and to identify effective predictive markers., Material and Methods: The expression of neuroendocrine markers, androgen receptor (AR) and androgen-regulated genes, as well as markers of aggressiveness, were analyzed by immunohistochemistry on a tissue microarray containing samples of 30 sNEPCa, either pure or admixed with conventional PCa, and including 14 cases diagnosed de novo and 16 cases subsequent to prior androgen deprivation., Results: Chromogranin A is a better marker of NE differentiation than synaptophysin in post-treatment NEPCa, with 94% and 44% of positive tumors, respectively, while both markers are equally expressed in de novo cases. Despite the acquisition of a NE phenotype, more than half of NEPCa expressed AR and the androgen-regulated gene NKX3.1, more frequently in cases admixed with conventional PCa. TTF1 staining, present in half of NEPCa, was associated with loss of androgen-regulated genes and with markers of aggressiveness, including increased proliferation, Zeb1 expression and PTEN loss. In multivariate analysis, only TTF1 expression was significantly associated with shorter overall survival., Conclusion: These results suggest the persistence of androgen signaling in a number of NEPCa cases, and the interest of TTF1 staining as a predictive biomarker., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hormone deprivation therapies play a key role in the treatment of prostate cancer. These treatments require standardized care and regular monitoring. The objective of this work was to review the different hormonal therapies available, their side effects and the role of a coordinating nurse in the management of these therapies. First generation hormone therapy is the standard treatment for metastatic prostate cancer. In the past years, second generation hormone therapies have been indicated in combination with first-generation hormone therapies at different stages of the disease. These molecules are responsible for several side effects that should be monitored and prevented. Thus, after an initial assessment, clinical and paraclinical follow-up are essential. Our center has set up monitoring by a coordinating nurse (IDEC) to optimize the education and follow-up of the patient, but also to provide psychosocial support adapted throughout the patient's care path under hormone therapy. This monitoring and information function by IDEC can be facilitated by new digital solutions., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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

Context: Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear., Objective: To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients., Evidence Acquisition: A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations., Evidence Synthesis: Ten-year biochemical recurrence (BCR)-free, clinical recurrence-free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events., Conclusions: While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients., Patient Summary: Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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

The 2019 Briganti nomogram was developed to calculate the risk of lymph node invasion (LNI) and identify prostate cancer (PCa) patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy who should be considered for an extended pelvic lymph node dissection (ePLND). Since its implementation is still limited by lack of a formal external validation, we aimed to validate this tool in a large contemporary cohort. We identified 487 patients diagnosed using MRI-targeted with concomitant systematic biopsy who underwent radical prostatectomy (RP) and an anatomically defined ePLND at six centers. The external validity of the 2019 Briganti nomogram for estimating LNI risk was assessed via calibration, discrimination, and decision curve analyses (DCAs). A total of 38 (8%) patients had LNI at final pathology. The median number of nodes removed was 18 (interquartile range 14-24). On external validation, the 2019 Briganti nomogram had an area under the receiver operating characteristic curve (AUC) of 79%. Although there was some miscalibration, this was at predicted probabilities >35% and therefore outside the clinically relevant range. DCA demonstrated that the 2019 Briganti nomogram improved clinical risk prediction against LNI threshold probabilities of ≤30%. For a 7% cutoff, 273 (56%) ePLNDs would be spared and only 2.6% LNIs would be missed. The 2019 Briganti nomogram was characterized by higher AUC compared to the 2012 and 2017 Briganti nomograms and the Memorial Sloan Kettering Cancer Center risk calculator (79% vs 75% vs 65% vs 74%) and demonstrated the highest net benefit on DCA. This first multi-institutional validation of the 2019 Briganti nomogram in predicting LNI in PCa patients diagnosed with MRI-targeted biopsy confirms the highest AUC, better calibration and the highest net benefit compared with available tools and should be adopted to identify candidates for ePLND among men diagnosed with MRI-targeted biopsy. PATIENT SUMMARY: We performed the first multi-institutional validation of the first nomogram predicting lymph node invasion specifically developed using data from prostate cancer patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. This nomogram exhibited excellent characteristics on external validation compared with available tools and should be adopted to identify candidates for extended pelvic lymph node dissection among men diagnosed with MRI-targeted biopsy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of the Cancerology Committee of the French Association of urology (CCAFU) is to propose an update of the guidelines in the management of hormone-sensitive metastatic prostate cancer., Methods: A systematic review (Medline) of the literature from 2018 to 2020 was conducted by the CCAFU Findings. Several patterns can be defined at this stage depending on prognostic, metastatic volume, and whether metastases are synchronous or metachronous. Androgenic deprivation therapy (ADT) remains the mainstay of treatment at the metastatic stage. Docetaxel in combination with ADT improves overall 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 have led to the recommendation that ADT should be used in conjunction with a new generation 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. Metastases-directed therapy is being evaluated., Conclusion: This update of the French recommendations should help improve the management of patients with prostate cancer., (Copyright © 2020. Published by Elsevier Masson SAS.)

Prostate cancer (PCa) remains the most common cancer in men. The proportion of all PCa attributable to high-risk hereditary factors has been estimated to 5-15%. Recent landmark discoveries in PCa genetics led to the identification of germline mutations/alterations (eg. BRCA1, BRCA2, ATM or HOXB13), single nucleotide polymorphisms or copy number variations associated with PCa incidence and progression. However, offering germline testing to men with an assumed hereditary component is currently controversial. In the present review article, we provide an overview about the epidemiology and the genetic basis of PCa predisposition and critically discuss the significance and consequence in the clinical routine. In addition, we give an overview about genetic tests and report latest findings from ongoing clinical studies. Lastly, we discuss the impact of genetic testing in personalized therapy in advanced stages of the disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this article is to present adapted physical activity (APA) and its potential impact on the androgen deprivation therapy (ADT) adverse effects, the limits and measures to promote its use among prostate cancer (PCa) patients treated with ADT., Material and Methods: A non-systematic review of the literature was performed with pubmed referenced articles, using the keywords "prostate cancer", "androgen deprivation" and "physical activity", and the main publications and recommendations of national and international health agencies, published between January 2010 and June 2019., Results: APA represents an effective action to reduce adverse effects of ADT. Its integration into health care of PCa patients treated with ADT remains limited., Conclusion: To promote a APA development in this population, a multidisciplinary collaboration between healthcare and APA professionals is essential. This collaboration should enable implementation of standard and innovative APA programs and therapeutic education tools for patients, as well as development of information and promotion for healthcare professionals., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Context: Identification of early nodal recurrence after primary prostate cancer (PCa) treatment by functional imaging may guide metastasis-directed therapy such as salvage lymph node dissection (SLND)., Objective: The aim of this systematic review was to assess the oncological role and the safety of SLND in the era of modern imaging in case of exclusive nodal recurrence after primary PCa treatment with curative intent., Evidence Acquisition: A systematic literature search in the PubMed and Cochrane databases was performed up to August 2018 according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Overall, 27 SLND series have been selected for synthesis., Evidence Synthesis: Prostate-specific membrane antigen or choline positron emission tomography/computed tomography was the reference detection technique. SLND was performed by open or laparoscopic approach with <10% of grade 3 or more complication rate. Mean follow-up was 29.4 mo. Complete biochemical response after SLND was achieved in 13-79.5%of cases (mean 44.3%). The 2- and 5-yr biochemical progression-free survival rates ranged from 23% to 64% and from 6% to 31%, respectively. Fiver-year overall survival was approximately 84%. Main drawbacks limiting the interpretation of the effectiveness of SLND were the retrospective design of single-center series, heterogeneity between series in terms of adjuvant treatment, endpoints, definitions of progression and study population, as well as the absence of long-term follow-up., Conclusions: A growing body of accumulated data suggests that SLND is a safe metastasis-directed therapy option in nodal recurrence after primary treatment. However, to date, high level of evidence is still missing to draw any clinically meaningful conclusion about the oncological impact of SLND on long-term endpoints., Patient Summary: When imaging identifies exclusive nodal recurrent prostate cancer, surgery directed to the positive lesions is safe and can offer at least a temporary biochemical response. The oncological role assessed by strong clinical endpoints remains uncertain., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: This study sought to compare the incidental prostate cancer (iPCa) detection rate between pathological specimens from green laser enucleation of the prostate (GreenLEP) and open simple prostatectomy (OSP)., Materials and Methods: In two institutions, the charts of all consecutive patients who underwent OSP between January 2005 and December 2010 were retrospectively reviewed, and the data of all consecutive patients who underwent GreenLEP with tissue morcellation between July 2013 and January 2018 were also collected. Preoperative demographics and pathological findings were recorded. iPCa detection rate was retrospectively compared between the GreenLEP and OSP groups in a propensity score model, including all predetermined variables: Age, preoperative PSA level and prostate volume., Results: Of 738 patients, 402 were included in the propensity-score matching analysis, and they were equally distributed among groups. The overall iPCa detection rates were similar in both groups (9.9% vs. 8.5%; p = 0.73), and there were no statistically significant differences in terms of tumour stage, Gleason score or the rate of clinically significant iPCa, although the number of cassettes analysed was significantly higher in the morcellation group than in the OSP group. No predictive factors for iPCa were identified., Conclusions: The results of the present study suggest that the mechanical morcellation of large glands had no influence on iPCa detection. Compared with a specimen from standard OSP, a large morcellated tissue sample allows adequate pathological evaluation and does not alter a pathologist's ability to detect iPCa.

Objective: To evaluate the feasibility of routine outpatient management after robotic-assisted radical prostatectomy (RARP). Prostate cancer is indeed the second most common cancer in men. Surgical technics have evolved from open surgery to robot-assisted surgery with a reduction of postoperative complications. Such technical improvements associated with modern anesthesia allow outpatient surgery in various types of procedures., Material and Methods: After approval of the IRB, this observational prospective and monocentric study was performed in the urology unit at Rennes University Hospital between December 2015 and October 2017. All patients scheduled for RARP performed by one experienced surgeon were consecutively included. The possibility of discharge was evaluated using the Post Anesthesia Discharge Scoring System (PADSS) score until patients had a score of 9 or higher allowing their discharge. Risk factors of delayed discharge were secondarily assessed RESULTS: Ninety-seven patients scheduled for RARP performed by one experienced surgeon were consecutively included. Only 1 patient had a PADSS score ≥ 9 the day of the surgery (day 0). Seventy-four percent of the patients achieved discharge criteria 1 day after surgery whereas, 33% and 66% of the population was effectively discharged on day 2 and day 3, respectively. Patients with a PADSS score ≥ 9 at day 1 experienced significantly less postoperative nausea and vomiting than patients with a PADSS score ≥ 9 at day 2 or 3 (7% vs 28%, P = .01)., Conclusion: Outpatient RARP was not feasible in most patients. However, routine discharge at day 1 seems conceivable. Improving the management of postoperative nausea and vomiting may even allow outpatient management. This progress remains to be confirmed by further studies., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess the economic impact of introducing the prostate health index (phi) for prostate cancer (PCa) detection., Methods: A total of 177 patients who presented in an academic institution with a tPSA between 2 and 10 ng/ml and underwent prostate biopsies within the 3 months were enrolled. With phi and tPSA thresholds of 43 and 4 ng/ml, respectively, probability for each branch of a decision tree model for PCa diagnosis and corresponding mean cost were estimated with "Monte Carlo" simulations. A sensitivity analysis was performed., Results: With a similar sensitivity, phi strategy increased positive predictive value by 13.9 points and negative predictive value by 31.6 points in comparison to tPSA strategy. Mean costs per patient with tPSA and phi strategies were €514 and €528, respectively, for a phi test price at 50€. One-way sensitivity analysis showed that phi strategy was less expensive (508€/patient) than tPSA strategy with a phi test price below 30€. In multi-criteria sensitivity analysis, PPV and the rates of positive phi and tPSA were the parameters with the largest impact on the final cost as opposed to the cost of the biopsy or imaging which have less influence. With an expected rate of positive phi test < 60%, tPSA strategy was more expensive than phi strategy., Conclusions: The introduction of phi index in PCa detection would result in a significant clinical benefit compared to tPSA strategy. In our economic model, the phi strategy was equivalent or slightly more expensive than the current tPSA strategy.

Purpose: The diagnostic strategy implementing multiparametric magnet resonance tomography (mpMRI) and targeted biopsies (TB) improves the detection and characterization of significant prostate cancer (PCa). We aimed to assess the clinical usefulness of systematic biopsies (SB) in the setting of patients having a pre-biopsy positive MRI., Methods: A review of the literature was performed in March 2018. All studies investigating the performance of SB in addition to TB (all techniques) were assessed, both in the biopsy-naïve and repeat biopsy setting., Results: Evidence demonstrates that TB improves the detection of index-significant PCa compared with SB alone, in both initial and repeat biopsy settings. However, the combination of both TB and SB improved the overall (around 30%) and significant (around 10%) PCa detection rates as compared with TB alone. Significant differences between both biopsy approaches exist regarding cancer location favoring SB for the far lateral sampling, and TB for the anterior zone. Main current pitfalls of pure TB strategy are the learning curve and experience required for mpMRI reading and biopsy targeting, as well as the precision assessment in TB techniques., Conclusion: A pure TB strategy omitting SB leads to the risk of missing up to 15% of significant cancer, due to limitations of mpMRI performance/reading and of precision during lesion targeting. SB remain necessary, in addition to the TB, to obtain the most accurate assessment of the entire prostate gland in this sub-group of patients at risk of significant disease.

Background: Serum cholinesterase (ChE) a serine hydrolase that catalyses the hydrolysis of esters of choline, is involved in cellular proliferation and differentiation, therefore affecting carcinogenesis. The aim of this study was to understand the prognostic role of preoperative serum ChE in patients with radiation-recurrent prostate cancer (CaP) treated with salvage radical prostatectomy (SRP)., Material and Methods: This retrospective study included 214 patients with radiation-recurrent CaP treated with SRP from January 2007 to December 2015 at 5 academic centers. Patients were considered with abnormal/decreased ChE levels if <5 kU/l. Biochemical recurrence-free and metastases-free (MFS) survival analyses were performed., Results: Median serum ChE level was 6.9 (interquartile range) 6-7.7) kU/l. Serum ChE level (<5 kU/l) was decreased in 25 (11.7%) patients. Decreased serum ChE level was associated with lower body mass index (P = 0.006) and metastasis to lymph nodes (P = 0.004). In multivariable analysis, continuous ChE was an independent predictor of MFS (hazard ratio [HR] 0.48, confidence interval [CI] 0.33-0.71, P < 0.001), overall survival (HR 0.68, CI 0.48-0.96, P = 0.03) and cancer-specific survival (HR 0.41, CI 0.2-0.84, P = 0.01). Serum ChE improved the C-index (by 2.54%) to 87.8% for prediction of overall survival and (by 3%) to 92% for prediction of MFS., Conclusion: Preoperative serum ChE is associated with the development of metastasis in patients with radiation-recurrent CaP who underwent SRP. The biological underpinning of this association with the biological and clinical aggressiveness of CaP needs to be further elucidated., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer., Materials and Methods: We conducted a retrospective analysis of our multi institutional database. Preoperative ChoE was evaluated as continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with biochemical recurrence (BCR)-free survival. We assessed its association with perioperative clinicopathologic characteristics and outcomes. Multivariable models established its independent prognostic value for BCR. Cox proportional hazard coefficients were used to build nomograms for the prediction of early and late BCR. Decision curve analysis was used to assess the clinical impact on decision making of preoperative ChoE., Results: In all, 6,041 patients were available for the analysis. Decreased ChoE was associated with higher biopsy Gleason score, preoperative PSA levels, pathologic Gleason score, pathological stage, lymph node metastasis, positive surgical margin, and lymphovascular invasion at radical prostatectomy (all P < 0.01). Preoperative ChoE ≤ 6.52 U/ml was associated with higher probability of BCR (HR 1.72, 95% CI 1.48-1.99, P < 0.001). Preoperative and postoperative multivariable models that adjusted for the effects of established clinicopathologic features confirmed its independent association with BCR. In decision curve analysis inclusion of preoperative ChoE did not improve the net benefit of preoperative and postoperative models for the prediction of BCR., Conclusions: Despite independent association with clinicopathologic features and BCR, preoperative serum ChoE has no impact on clinical decision making. Future studies should investigate the possible relationship between ChoE activity and neoplastic cell transformation with a rational for targeting., (Copyright © 2018. Published by Elsevier Inc.)

Background: Commercial gene expression assays are guiding clinical decision making in patients with prostate cancer, particularly when considering active surveillance. Given heterogeneity and multifocality of primary prostate cancer, such assays should ideally be robust to the coexistence of unsampled higher grade disease elsewhere in the prostate in order to have clinical utility. Herein, we comprehensively evaluated transcriptomic profiles of primary multifocal prostate cancer to assess robustness to clinically relevant multifocality., Methods: We designed a comprehensive, multiplexed targeted RNA-sequencing assay capable of assessing multiple transcriptional classes and deriving commercially available prognostic signatures, including the Myriad Prolaris Cell Cycle Progression score, the Oncotype DX Genomic Prostate Score, and the GenomeDX Decipher Genomic Classifier. We applied this assay to a retrospective, multi-institutional cohort of 156 prostate cancer samples. Derived commercial biomarker scores for 120 informative primary prostate cancer samples from 44 cases were determined and compared., Results: Derived expression scores were positively correlated with tumor grade (rS = 0.53-0.73; all P < 0.001), both within the same case and across the entire cohort. In cases of extreme grade-discordant multifocality (co-occurrence of grade group 1 [GG1] and ≥GG4 foci], gene expression scores were significantly lower in low- (GG1) versus high-grade (≥GG4) foci (all P < 0.001). No significant differences in expression scores, however, were observed between GG1 foci from prostates with and without coexisting higher grade cancer (all P > 0.05)., Conclusions: Multifocal, low-grade and high-grade prostate cancer foci exhibit distinct prognostic expression signatures. These findings demonstrate that prognostic RNA expression assays performed on low-grade prostate cancer biopsy tissue may not provide meaningful information on the presence of coexisting unsampled aggressive disease., Funding: Prostate Cancer Foundation, National Institutes of Health (U01 CA214170, R01 CA183857, University of Michigan Prostate Specialized Program of Research Excellence [S.P.O.R.E.] P50 CA186786-05, Weill Cornell Medicine S.P.O.R.E. P50 CA211024-01A1), Men of Michigan Prostate Cancer Research Fund, University of Michigan Comprehensive Cancer Center core grant (2-P30-CA-046592-24), A. Alfred Taubman Biomedical Research Institute, and Department of Defense.

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

Introduction: The purpose of the present study was to investigate the association of smoking with biochemical recurrence (BCR) and metastasis in radiation-recurrent prostate cancer (PCa) patients undergoing salvage radical prostatectomy (SRP)., Patients and Methods: A total of 214 patients treated with SRP for radiation-recurrent PCa in 5 tertiary referral centers were included from January 2007 to December 2015. Kaplan-Meier analyses were used to assess the time to BCR and metastasis. Pre- and postoperative multivariable Cox proportional hazard regression models were fitted., Results: Overall, 120 (56.1%), 49 (22.9%), and 45 (21%) patients were never, former, and current smokers, respectively. Low-, medium-, and high-cumulative smoking exposure was registered in 59.8%, 16.4%, and 23.8% of cases, respectively. Patients with high cumulative smoking exposure had a significantly greater rate of a pathologic Gleason score of ≥ 8 (P = .01) and extracapsular extension (P = .004). Smoking status, cumulative smoking exposure, intensity, and duration were significantly associated with BCR-free survival (P < .001 for all). Smoking status, cumulative smoking exposure, and smoking intensity were significantly associated with metastasis-free survival (P = .03 for all). High cumulative smoking exposure was independently associated with BCR in both pre- (hazard ratio, 2.23; P = .001) and postoperative (hazard ratio, 1.64; P = .04) multivariable models adjusted for the effects of established clinicopathologic features. Smoking cessation did not affect either BCR- or metastasis-free survival (P = .56 and P = .40, respectively)., Conclusion: High cumulative smoking exposure was associated with the biologic and clinical aggressiveness of PCa in patients treated with SRP for radiation-recurrent disease. Smoking is a modifiable risk factor that detrimentally affected the outcomes, even in patients with advanced PCa., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP)., Materials and Methods: Records of 6,041 patients who were treated with RP between 2000 and 2011 for clinically nonmetastatic PCa were, retrospectively, analyzed from prospectively collected datasets. BCR-free survival rates were assessed using univariable and multivariable cox-regression analyses., Results: Median patient age was 61 years (interquartile range [IQR]: 57-66) with a median preoperative prostrate specific antigen of 6ng/ml (IQR: 4-9). Overall, 28% of patients had Gleason score (GS) 6, 0.3% GS 6 + TGP, 33% GS 7 (3 + 4), 0.2% GS 7 (3 + 4) + TGP, 22% GS 7 (4 + 3), 0.2% GS 7 (4 + 3) + TGP, 0.1% GS 8 and 0.4% GS 9 or 10. Median follow-up was 45 months (IQR: 31-57). Harboring a TGP was associated with higher rates of positive surgical margins, lymphovascular invasion, extraprostatic extension, and seminal vesicle invasion than their counterparts within the same GS group as well as in the next higher GS group (all P ≤ 0.05). At 5 years post-RP, BCR estimates were 5% for patients with GS 6, 13% for patients with GS 6 + TGP, 6% for patients with GS 7 (3 + 4), 22% for patients with GS 7 (3 + 4) + TGP, 16% for patients with GS 7 (4 + 3), 41% for patients with GS 7 (4 + 3) + TGP, 38% for patients with GS 8 (4 + 4) and 46% for patients with GS 9 or 10. Patients harboring a TGP had higher BCR rates than the patients in the next higher GS group: GS 6 + TGP vs. GS 7 (3 + 4), HR = 1.6, P = 0.02 and GS 7 (3 + 4)+TGP vs. GS 7 (4 + 3), HR = 1.4, P = 0.03. Patients with a TGP in the GS 7 (4 + 3) group had comparable BCR rates as patients with GS = 8 (P = 0.4) and GS 9 to 10 (P = 0.2). On multivariable analysis that adjusted for the effects of preoperative prostrate specific antigen, nodal involvement, positive surgical margin, extraprostatic disease (pT3a), seminal vesicle invasion (pT3b) and different institution, harboring a TGP showed higher risk of developing BCR within the same GS group and comparable risk of developing BCR with the next higher GS group., Conclusion: Patients with TGP at RP have adverse clinicopathological features when compared to their counterparts in the same and the next higher GS group without TGP. Risk of developing BCR increases with the presence of TGP within the same GS group. This risk seems to be comparable between patients with TGP and their counterparts in the next higher GS group without TGP. Knowledge of TGP in RP specimens is likely to improve risk stratification, patient counseling and follow-up scheduling. Further prospective studies that control significant clinical endpoints such as metastasis and mortality are necessary for more significant predictions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 <10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans., Results: FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid., Conclusion: These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness., (Copyright © 2017 Elsevier Ltd. 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.)

Background: Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series., Methods: Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model., Results: Median follow-up was 48 months (95% CI = [45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4 years, HR = 1.97, 95% CI = [1.71; 2.27], p < 0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p < 0.0001). In multivariate analysis, primary Gleason score of 4 (HR = 1.81, 95% CI = [1.55; 2.12], p < 0.0001) and PPBC ≥ 50% (HR = 1.26, 95% CI = [1.02; 1.56], p = 0.0286) were significant preoperative predictors for worse PSA-RFS., Conclusions: This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

External radiotherapy is a major clinical treatment for localized prostate cancer. Currently, computed tomography (CT) is used to delineate the prostate and to plan the radiotherapy treatment. However, CT images suffer from a poor soft-tissue contrast and do not allow an accurate organ delineation. On the contrary, magnetic resonance imaging (MRI) provides rich details and high soft-tissue contrast, allowing tumor detection. Thus, the intraindividual propagation of MRI delineations toward the planning CT may improve tumor targeting. In this paper, we introduce a new method to propagate MRI prostate delineations to the planning CT. In the first step, a random forest classification is performed to coarsely detect the prostate in the CT images, yielding a prostate probability membership for each voxel and a prostate hard segmentation. Then, the registration is performed using a new similarity metric which maximizes the probability and the collinearity between the normals of the manual registration (MR) existing contour and the contour resulting from the CT classification. The first study on synthetic data was performed to analyze the influence of the metric parameters with different levels of noise. Then, the method was also evaluated on real MR-CT data using manual alignments and intraprostatic fiducial markers and compared to a classically used mutual information (MI) approach. The proposed metric outperformed MI by 7% in terms of Dice score coefficient, by 3.14 mm the Hausdorff distance, and 2.13 mm the markers position errors. Finally, the impact of registration uncertainties on the treatment planning was evaluated, demonstrating the potential advantage of the proposed approach in a clinical setup to define a precise target.

Background: There are no clear data regarding the association between body mass index (BMI) and outcomes after radical prostatectomy (RP). This study aimed to investigate the association between BMI and biochemical recurrence (BCR) after RP in a large international contemporary cohort of patients with prostate cancer., Methods: We retrospectively analyzed data from 6,519 patients who underwent RP at 5 institutions. BMI was analyzed as both a continuous and categorical variable (<25kg/m 2 , 25-29.9kg/m 2 [overweight], and≥30kg/m 2 [obese]). The associations of continuous and categorical BMI with BCR were evaluated using univariable and multivariable Cox models, and prognostic accuracy was assessed using Harrell׳s C-index., Results: The median BMI was 28kg/m 2 (interquartile range: 24-32kg/m 2 ); 2,155 patients (33.1%) had a BMI = 25 to 29.9kg/m 2 and 2,462 patients (37.7%) had a BMI≥30kg/m². Overweight and obese status were associated with extracapsular extension (P = 0.001) and seminal vesicle invasion (P = 0.005). The median follow-up was 28 months, and the estimated 5-year BCR-free survival rates for patients with a BMI<25kg/m 2 , 25 to 29.9kg/m 2 , and≥30kg/m² were 92%, 86%, and 79%, respectively (P<0.001). Multivariable analyses (adjusted for preoperative prostate-specific antigen levels, biopsy Gleason score, and clinical stage) revealed that obesity was associated with the risk of extracapsular extension (P<0.001), seminal vesicle invasion (P<0.001), and BCR (hazard ratio: 1.37, P<0.001). BMI and obesity remained associated with BCR after adjusting for postoperative characteristics. Addition of BMI slightly increased the discrimination of the multivariable clinical prognostic model (from 79.9%-80.9%)., Conclusions: Overweight and obese status was associated with adverse pathological features and BCR after RP. However, the addition of BMI did not significantly improve the prognostic accuracy of a model that was based on established predictors., (Copyright © 2017. Published by Elsevier Inc.)

Background: We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP)., Methods: Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index., Results: Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model)., Conclusions: We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.