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.

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).

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.

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.

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.

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.

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.

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.

Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech.

Haralick textural features on T2 -weighted MRI are associated with biochemical recurrence following radiotherapy for peripheral zone prostate cancer.

PURPOSE: To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. MATERIALS AND METHODS: In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T2 -weighted sequences (T2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. RESULTS: Three T2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T2 -w contrast, T2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. CONCLUSION: T2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:103-117.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

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.

MRI assessment of tissue effects after 180-W XPS greenlight laser vaporization of the prostate.

BACKGROUND AND OBJECTIVE: Photoselective vaporization of the prostate (PVP) is an alternative to transurethral resection of the prostate (TURP) in the surgical management of Benign Prostate Obtruction (BPO), with a better hemostatic effect due to a coagulation depth of several millimeters. The objective of this study was to prospectively assess the tissue effects of PVP by Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: From December to February 2014, ten patients were included in a prospective study and underwent PVP performed by a single surgeon with the Greenlight™ laser 180-W XPS. A multiparametric MRI of the prostate (Siemens 3T Verio) was achieved the day before the procedure and post-operatively (2 days, 7 days, 3 and 6 months after the procedure). The prostate volume after tissue removal was determined. The depth of necrosis in the prostatic and peri-prostatic tissues were assessed at six different locations. RESULTS: The median age and pre-operative prostate volume were 70 years (64-76) and 48.1 ml (19-74.4), respectively. Median prostate volume significantly decreased post-operatively (P < 0.001): At 6 months, median prostate volume reduction was 44.2% (38.7-49.5) (P = 0.001) compared to pre-operative setting. Two and 7 days after the procedure, mean depths of necrosis were 2.5 mm (0-3) and 1.3 mm (0-2.4), respectively. No necrosis was reported 3 and 6 months after the procedure. CONCLUSIONS: PVP with Greenlight™ XPS 180-W is associated with a significant reduction of prostate volume. The depth of necrosis is low and homogeneous, resulting in a limited risk of peri-operative complications. Lasers Surg. Med. 49:577-581, 2017. © 2017 Wiley Periodicals, Inc.

The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years.

OBJECTIVES: To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. PATIENTS AND METHODS: The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × âˆšt-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). RESULTS: In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter and the base model + PHI were equivalent with threshold probability and net benefit nearing those of the ANN. For significant cancers the ANN was the strongest parameter in DCA. CONCLUSION: The present multicentre study showed that %p2PSA and PHI have a superior diagnostic performance for detecting prostate cancer in the PSA range of 1.6-8.0 ng/mL compared with t-PSA and %f-PSA at initial and repeat biopsy and for predicting significant prostate cancer in men aged ≤65 years. They are equally superior for counselling patients before biopsy.

Artificial urinary sphincter implantation in women with stress urinary incontinence: preliminary comparison of robot-assisted and open approaches.

INTRODUCTION AND HYPOTHESIS: We aimed to compare outcomes of open and robot-assisted artificial urinary sphincter (AUS) implantation in female patients. METHODS: The charts of all female patients who underwent an AUS implantation between 2008 and 2014 in a single center were retrospectively reviewed. From 2008 to 2012, AUS were implanted using an open approach and from 2013 to 2014 using a robot-assisted approach. Perioperative and functional parameters were compared between groups. The primary endpoint was continence status. RESULTS: Twenty-four women were assessed: 16 in the open group and eight in the robot-assisted group. Three patients had neurogenic stress urinary incontinence. Most patients had undergone previous procedures for urinary incontinence (15 in the open group and seven in the robotic group). Mean operative time was similar in both groups (214 vs. 211 min; p = 0.90). Postoperative complicationsrate was lower in the robot-assisted group (25 vs. 75 %; p = 0.02). There was a trend toward a lower intraoperative complication rate (37.5 vs. 62.5 %; p = 0.25), decreased blood loss (17 ml vs. 275 ml; p = 0.22), and shorter length of stay (3.5 vs. 9.3 days; p = 0.09) in the robot-assisted group. Continence rates were comparable in both groups (75 vs. 68.8 %; p = 0.75). Three AUS explantations were needed in the open group (18.8 %) compared with one in the robot-assisted group (12.5 %; p = 0.70). CONCLUSIONS: In female patients, the robot-assisted approach compared with open AUS implantation could decrease intraoperative and postoperative complication rates, length of hospital stay, and blood loss.

Prospective evaluation of ambulatory laser vaporization of the prostate for benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVE: Photoselective vaporization of the prostate (PVP) is an alternative to transurethral resection of the prostate in the surgical treatment of benign prostatic hyperplasia (BPH). Our objective was to prospectively evaluate the feasibility, safety, and efficacy of ambulatory photoselective vaporization of the prostate for benign prostatic hyperplasia. MATERIALS AND METHODS: We prospectively collected data of all consecutive patients who underwent ambulatory PVP with the Greenlight(®) laser 180-W XPS at two centers between May 2012 and June 2013. Patients' characteristics, perioperative data, postoperative outcomes, complications, and patient's satisfaction were evaluated. Successful ambulatory care procedure was defined as the ability to leave the hospital in the evening of the operation. RESULTS: The ambulatory procedure was intended in 134 patients. Mean age was 67 years. Mean prostate volume was 54 ml, and Median American Society Anesthesiologists (ASA) score was 2. Ambulatory procedure was successful in 121 patients (90%). At 3 months, International Prostate Symptom Score (7.3 ± 4.9), maximal urinary flow rate (20.8 ± 7.6 ml/s), postvoid residual urine (19.2 ± 71 ml), and quality of life (1.6 ± 1.4) were significantly improved (P < 0.001). Fourteen patients (10.5%) had complications that were all minor (Clavien ≤ 2). Two patients had to be readmitted to the hospital. The majority of patients (89%) were satisfied with ambulatory care. Failure to complete ambulatory procedure was mostly related to logistical problem (70% of the cases). CONCLUSIONS: Ambulatory PVP is feasible with functional results and complications comparable to that of traditional hospitalization. Ambulatory care yields high patient's satisfaction.

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

PURPOSE: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). METHODS: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. RESULTS: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). CONCLUSIONS: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer.

BACKGROUND: Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [-2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA × âˆštPSA, was evaluated in a multicenter study for detecting PCa. METHODS: A total of 1362 patients from 4 different study sites who had tPSA values of 1.6-8.0 µg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS: The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score. CONCLUSIONS: The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6-8.0 µg/L (i.e., approximately 2-10 µg/L in traditional calibration) and is better able to detect aggressive PCa.

Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy.

PURPOSE: We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS: We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS: At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS: Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

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.