Real-World Treatment Patterns Among French Patients With Metastatic Castration-Resistant Prostate Cancer Under Abiraterone or Enzalutamide.

PURPOSE: Using large French retrospective study cohort of chemotherapy-naïve metastatic castration-resistant prostate cancer patients (mCRPC; n = 10,308) comparing survival between patients who initiated abiraterone (ABI; 64%) and those initiating enzalutamide (ENZ; 36%), the present objective was to describe treatment patterns in the 2 years following initiation. METHOD: Using the national health data system (SNDS) from 2014 to 2018, we first explored the number of treatment lines, and secondly, patterns of patient management using state sequence analysis; cluster analyses were performed on the 0 to 12 month and 13 to 24 month periods. Age, Charlson score, and duration of androgen deprivation therapy (ADT) were obtained for each cluster in the first year of follow-up. RESULTS: Patients with only 1 treatment line accounted for 52%. In the 0 to 12 month sequence analysis, the main clusters among ABI/ENZ new users involved patients who continued the initial treatment (54% of 65% respectively) and discontinued active treatment (14.5% for both). Less than 2 years exposure to ADT prior to ABI/ENZ initiation was frequently observed for noncontrolled mCRPC, as shown in the death and switch from ABI/ENZ to docetaxel clusters. The clusters for a switch ABI/ENZ to ENZ/ABI involved 6% to 11% of the patients. CONCLUSION: Our study suggested fairly similar patterns between ABI and ENZ initiation. The cluster of patients with active treatment discontinuation needs to be further investigated, as well as factors influencing therapeutic choice. Better understanding for the use of second-generation hormone therapy in mCRPC in real life, could improve its implementation by clinicians in the early stages of prostate cancer.

Pattern of Clinical Progression Until Metastatic Castration-Resistant Prostate Cancer: An Epidemiological Study from the European Prostate Cancer Registry.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in men in Europe. The impact of PCa natural history and therapeutic management on the outcomes of castration-resistant prostate cancer patients with metastasis (mCRPC) remains unclear. OBJECTIVE: The objective of this study was to describe retrospectively patterns of clinical progression through diagnosis sequences before the mCRPC stage and to assess how these sequences impacted patients' disease progression and overall survival at mCRPC stage. PATIENTS AND METHODS: Patients with mCRPC were identified from the Prostate Cancer Registry (PCR), an observational study in a real-world setting in 16 countries between 2013 and 2016. Patients were grouped in diagnosis sequences before mCRPC and defined by date of PCa diagnosis, first metastasis, and castration resistance. Distribution of time-to-event variables were estimated using Kaplan-Meier product-limit survival curves for overall survival (OS) and progression-free survival (PFS). Non-adjusted Cox models were conducted for efficacy endpoints (OS, PFS) to estimate hazard ratios between diagnosis sequences. RESULTS: At the end of study, 2859 mCRPC patients were included in this analysis. Among mCRPC four diagnosis sequences were identified: 35% developed metastases (mHSPC) before becoming castration resistant (sequence 1, metachronous mHSPC), 10% developed castration resistance (nmCRPC) before metastases (sequence 2), 27% developed metastases and castration resistance within 4 months (sequence 3) and 28% of patients were de novo mHSPC (sequence 4). Median OS was 17.7 months (interquartile range (IQR): 8.8-29.9) and PFS was 6.4 months (IQR: 3.2-12.0). The univariate analyses showed no correlation between mCRPC patients' OS or PFS and the diagnosis sequence. CONCLUSION: This large European study describe four different patterns of prostate cancer progression to mCRPC stage. Our results indicate that patient survival becomes comparable after progression to mCRPC, regardless of the diagnosis sequence. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.

Hospitalization for adverse events under abiraterone or enzalutamide exposure in real-world setting: A French population-based study on prostate cancer patients.

AIMS: Safety profiles of abiraterone and enzalutamide rely mainly on Phase III clinical trials. Our objective was to estimate the incidence rate ratio (IRR) for certain adverse events leading in real life to hospitalization (atrial fibrillation, acute heart failure, ischaemic heart disease, acute kidney injury [AKI], ischaemic stroke, torsade de pointe/QT interval prolongation, hepatitis and seizure), comparing abiraterone to enzalutamide. We also set out to discuss previously identified safety signals. METHOD: Using the French National Health Insurance System database, all patients newly exposed to abiraterone or enzalutamide between 2013 and 2017 and followed until 31 December 2018 were targeted. IRRs for each event were estimated using a Poisson model in a sub-population of patients without contraindications or precautions for use for either treatment. RESULTS: Among 11 534 new users of abiraterone and enzalutamide, AKI (IRR 1.42, 95% CI: 1.01-2.00), liver monitoring suggestive of hepatic damage (IRR 3.06, 95% CI: 2.66-3.53) and atrial fibrillation (IRR 1.12, 95% CI: 1.05-1.19) were significantly more often observed with abiraterone than with enzalutamide. CONCLUSION: Our study provides knowledge on abiraterone and enzalutamide real-life safety profiles, especially for events leading to hospitalization. Despite several limitations, including the lack of clinical data, the safety signal for AKI under abiraterone is in line with results of an analysis of the French pharmacovigilance database, which requires further specific investigations. Enlightening the clinicians' therapeutic choices for patients treated for prostate cancer, our study should lead to clinicians being cautious in the use of abiraterone.

Changes in prostate cancer screening practice by blood PSA testing between 2011 and 2017, a French population-based study.

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.

Apalutamide, darolutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer: a meta-analysis.

Aim: Comparison of the efficacy/safety/health-related quality of life of apalutamide, enzalutamide and darolutamide in Phase III clinical trials involving patients with nonmetastatic castration-resistant prostate cancer was performed. Materials & methods: Relevant studies were identified by searching PubMed as well as conference abstracts reporting updated overall survival. Three pivotal trials were identified, SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), and form the basis of this analysis. Results: All three drugs significantly prolonged metastasis-free survival, prostate-specific antigen response and overall survival versus placebo, and were generally well tolerated. Conclusion: Drug selection will likely be influenced by tolerability/safety and other factors, such as the propensity for drug-drug interactions and the presence of comorbidities, that affect the risk-benefit balance in individual patients.

Androgen deprivation therapy prescription, blood and bone-density testing in a French population-based study exploring adherence to the French prostate cancer guidelines.

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.

Overall Survival Among Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer Under Abiraterone Versus Enzalutamide: A Direct Comparison Based on a 2014-2018 French Population Study (the SPEAR Cohort).

Abiraterone acetate (ABI) and enzalutamide (ENZ) are considered to be clinically relevant comparators among chemotherapy-naive patients with castration-resistant prostate cancer. No clinical trials comparing overall survival with ABI versus ENZ in a head-to-head approach have been published so far. A few observational studies with low power suggested a potential benefit of ENZ. We used the French National Health Data System to compare overall survival of new users of ABI and ENZ among chemotherapy-naive patients with castration-resistant prostate cancer in 2014-2017, followed through 2018 (the SPEAR cohort, a 2014-2018 cohort study). With an intent-to-treat approach, a survival analysis was performed, estimating hazard ratios for overall survival with the inverse probability weighted Cox model method. Among 10,308 new users, 64% were treated with ABI and 36% with ENZ. The crude mortality rate was 25.2 per 100 person-years (95% confidence interval (CI): 24.4, 26.0) for ABI and 23.7 per 100 person-years (95% CI: 22.6, 24.9) for ENZ. In the weighted analysis, ENZ was associated with better overall survival compared with ABI (hazard ratio = 0.90 (95% CI: 0.85, 0.96) with a median overall survival of 31.7 months for ABI and 34.2 months for ENZ). When restricting to 2015-2017 new users, the effect estimate shifted up to a hazard ratio of 0.93 (95% CI: 0.86, 1.01).

The surgical learning curve for endoscopic GreenLight™ laser enucleation of the prostate: an international multicentre study.

OBJECTIVES: To investigate the effect of surgical experience on the perioperative outcomes of endoscopic GreenLight™ (Boston Scientific Corporation, Marlborough, MA, USA) laser enucleation of the prostate (GreenLEP). SUBJECTS/PATIENTS AND METHODS: A multicentre retrospective study of the first patients treated with GreenLEP by six surgeons was conducted. For each patient, surgical experience was coded as the total number of procedures performed by the surgeons before the patient's operation. The learning curve was analysed in terms of changes over time for the following variables: enucleation time, morcellation time, occurrence of intraoperative complications (IOCs), 3-month postoperative International Prostate Symptom Score (IPSS) reduction, and the rate of Pentafecta achievement. RESULTS: In total, 922 patients were analysed. At multivariable regression analyses adjusted for case mix, surgical experience was associated with shorter enucleation and morcellation time (P < 0.001), lower IOC rate (P < 0.001), higher 3-month postoperative reduction in IPSS (P = 0.004), and higher probability of Pentafecta achievement (P < 0.001). The relationship between surgical experience and enucleation time/IOCs appeared as non-linear, with a steep slope reduction within the first 100 cases and a plateau observed after 200 cases, whilst the IPSS improved rapidly early in the learning curve process and plateaued after ~100 procedures. Finally, there was a linear improvement in Pentafecta achievement, with a plateau observed after 270 cases. CONCLUSION: Surgical experience has a significant impact on the perioperative outcomes for GreenLEP procedures. After adjusting for patient and prostate characteristics, plateau results were achieved after a long learning curve. A more intensely mentored and structured training schedule might allow quicker and safer adoption of the procedure.

Determinants and prognostic value of post-operative maximum urethral closure pressure after artificial urinary sphincter in men.

PURPOSE: To evaluate the determinants and prognostic value of post-operative maximum urethral closure pressure (MUCP) after AUS implantation in male patients. METHODS: The charts of all male patients who had an AUS implantation between 2008 and 2018 at a single center were reviewed retrospectively for an exploratory study. A post-operative urethral profilometry was performed systematically as part of routine daily practice over the study period to assess the post-operative MUCP with the AUS consecutively closed (c-MUCP) and opened (o-MUCP). The difference between c-MUCP and the manufacturer's theoretical pressure objective determined by the pressure regulating balloon (PRB) was calculated (diff-th-MUCP). The primary endpoint was social continence at 3 months defined as 0-1 protection/day. RESULTS: Ninety patients were included. The median age was 71 years, and the median follow-up was 50 months. The etiology of incontinence was radical prostatectomy in 84% of cases, and endoscopic prostate surgery in 6.6% of patients. There were 74.4% of patients who were socially continent at 3 months. The c-MCUP was significantly higher in the continent group (53 [42.2, 60.2] vs 62 [58, 70] p = 0.02). The diff-th-MUCP did not differ significantly between the two groups (18 [0, 23] vs 1 [- 2, 7.7] p = 0.29). The c-MUCP was not statistically associated with the risk of revision and/or explantation. CONCLUSION: The MUCP after AUS implantation in male patients often differs from the manufacturer's pressure objective. The postoperative c-MUCP might be significantly associated with functional outcomes suggesting that it might be a valuable tool for treatment decision-making. This should be confirmed by larger studies.

Prospective Assessment of the Sexual Function After Greenlight Endoscopic Enucleation and Greenlight 180W XPS Photoselective Vaporization of the Prostate.

OBJECTIVE: To evaluate the impact of Greenlight 180W photoselective vaporization of the prostate (PVP) and endoscopic enucleation of the prostate (GreenLEP) on ejaculatory and erectile functions. MATERIALS AND METHODS: Between January 2014 and September 2016, 440 men with low urinary tract symptoms or complications related to benign prostate obstruction with prostate >80 g and sexually active, underwent a PVP or GreenLEP performed by experienced surgeons at a single institution. Patients were matched in a 1:1 fashion according to preoperative transrectal ultrasonography prostatic volume and cardiovascular risk factors (smoking, diabetes, and hypertension). RESULTS: One hundred patients in each group were included. Mean prostatic volume were 110 g (95%CI: 101-118) and 107 g (95%CI: 99-115) in the GreenLEP and PVP groups, respectively (P = .68). Mean total energy delivered in the PVP group was 4.42 kJ/g (4.2-4.6). Surgical retreatment was required in 9 patients (10.1%) in the PVP group and none in the GreenLEP group (log rank test: P = .002). Mean prostate specific antigen level and International Prostate Symptom Score score were significantly lower in the GreenLEP group than in the PVP group at 3, 12, and 24 months (P <.001). Preserved antegrade ejaculation was reported in 24 patients (26.9%) in the PVP group vs 1 patient (1.2%) in the GreenLEP group at 12 months (P <.001). In multivariate analysis, age, history of coronary artery disease, and surgical treatment with PVP were independent factors of IIEF-5 decline. CONCLUSION: Despite a poor rate of preserved antegrade ejaculation, GreenLEP was associated with better erectile function outcomes possibly due to greater improvement of low urinary tract symptoms.

Outpatient Robot-assisted Radical Prostatectomy: A Feasibility Study.

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.

Cost analysis of prostate cancer detection including the prostate health index (phi).

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.

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study.

OBJECTIVE: To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer. PATIENTS AND METHODS: We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design. RESULTS: A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8. CONCLUSION: Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2 years with 5-ARIs should be informed about the increased risk of development of high grade disease.

Radical Prostatectomy after Vascular Targeted Photodynamic Therapy with Padeliporfin: Feasibility, and Early and Intermediate Results.

PURPOSE: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. MATERIALS AND METHODS: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. RESULTS: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. CONCLUSIONS: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings.

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2-20ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2-10ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n=397) and for PSA 10-20ng/ml (n=439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used. PATIENT SUMMARY: The Prostate Health Index (PHI) blood test helps to identify individuals at higher risk of prostate cancer among Asian and European men, and could significantly reduce unnecessary biopsies and overdiagnosis of prostate cancer. Different PHI reference ranges should be used for different ethnic groups.

Does mechanical morcellation of large glands compromise incidental prostate cancer detection on specimen analysis? A pathological comparison with open simple prostatectomy.

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.

Stopping or maintaining oral anticoagulation in patients undergoing photoselective vaporization of the prostate (SOAP) surgery for benign prostate obstruction: study protocol for a multicentre randomized controlled trial.

BACKGROUND: Lower urinary tract symptoms related to benign prostatic obstruction (BPO) are frequent in men aged > 50 years. Based on the use of innovative medical devices, a number of transurethral ablative techniques have recently been developed for the surgical treatment of BPO. In recent years, GreenLight photoselective vaporization of the prostate (PVP) has been considered as a non-inferior alternative to transurethral resection of the prostate. The GreenLight PVP is usually considered as an interesting surgical option for patients treated via oral anticoagulants (OACs) with regard to its haemostatic properties. The aim of this study was to assess the impact of maintaining OAC treatment in patients undergoing PVP. METHODS: This study is a multicentre, open-label, randomized controlled trial (RCT) designed to show the non-inferiority of PVP surgery in patients with BPO treated with OACs. This study is designed to enrol 386 OAC-treated patients (treated with vitamin K antagonists and direct oral anticoagulants) who are undergoing PVP for BPO. Patients will be randomized (1:1) to either maintain or stop OAC treatment during the perioperative course. The intervention group will maintain OAC treatment until the day before surgery and resume OAC treatment the day after surgery, whereas the control group will stop OAC treatment (with or without low-molecular-weight heparin bridging therapy) according to the anaesthesia guidelines. The primary outcome of interest to be assessed is the 30-day complications rate according to the Clavien-Dindo classification. The secondary endpoint will examine the 30-day rate of haemorrhagic and thrombotic events. This study will provide 80% power to show non-inferiority, defined as not worse than a 10% (non-inferiority margin) inferior change in the proportion of patients with good outcomes (Clavien-Dindo score < 2), using two-tailed 95% confidence intervals. DISCUSSION: This first multicentre RCT in the field is underway to evaluate the safety and efficacy of PVP in patients with ongoing OAC therapy. The study results could influence the perioperative management of OACs in BPO surgery with a high level of evidence. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03297281 . Registered on 29 September 2017.

Management of non-metastatic castrate-resistant prostate cancer: A systematic review.

Management of non metastatic castrate resistant prostate cancer is challenging for clinicians due to the heterogeneity of the disease and to the scarce clinical data available in this setting. Recent results obtained with the new generation hormone therapies (NGHT) apalutamide and enzalutamide bring a new perspective for the treatment strategy. The authors present here a systematic review of the treatment options.

Systemic treatments for high-risk localized prostate cancer.

The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. However, although the combination of androgen deprivation therapy and radiotherapy is a standard of care in high-risk localized or locally advanced prostate cancer, the benefit of chemotherapy or chemohormonal therapy has yet to be demonstrated outside of the metastatic setting. Moreover, the benefit of neoadjuvant and/or adjuvant systemic therapies in combination with radical prostatectomy has not been proved. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials.

Fatty acid profile in peri-prostatic adipose tissue and prostate cancer aggressiveness in African-Caribbean and Caucasian patients.

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.