Evolution of anxiety management in prostate biopsy under local anesthesia: a narrative review.

INTRODUCTION AND METHODS: Prostate biopsy (PB) is an essential step in the diagnosis and active surveillance of prostate cancer (PCa). Transperineal PB (TP-PB) is now the recommended approach and is mostly conducted under local anesthesia. However, this procedure can potentially cause anxiety for patients, given the oncological context and the fear of peri-procedural pain and complications. The objective of this narrative review is to summarize the currently available tools for the management of peri-interventional anxiety during TP-PB, with a particular emphasis on the potential role of virtual reality (VR) in this setting. RESULTS: In TP-PB, preoperative anxiety can lead to increased pain perception, longer procedure time, and decreased patient satisfaction. Pharmacological and non-pharmacological approaches have been explored to reduce anxiety, such as premedication, deep sedation, education, relaxation techniques, hypnosis, and music therapy, albeit with mixed results. VR has recently emerged in the technological armamentarium for managing pain and anxiety, and the efficiency of this technology has been evaluated in various medical fields, including pediatrics, gastroenterology, urology, gynecology, and psychiatry. CONCLUSION: Despite the paucity of available data, VR appears to be a safe and effective technique in reducing anxiety in many procedures, even in frail patients. No studies have evaluated the role of VR in TP-PB. Future research should thus explore the optimal way to implement VR technology and any potential benefits for TP-PB patients.

[Benign prostatic hyperplasia treatment: Surgical alternatives to transurethral resection of the prostate]. / Traitement de l'hyperplasie bénigne de la prostate - Alternatives chirurgicales à la résection transurétrale de la prostate.

Benign prostatic hyperplasia is one of the most common diseases in ageing men and the most common cause of lower urinary tract symptoms. The gold standard of surgical treatments for benign prostatic hyperplasia for decades has been transurethral resection of the prostate. New minimally invasive techniques have been developed with the aim of reducing morbidity or resecting large prostate volumes endoscopically. In this article, we summarize the different surgical alternatives to transurethral resection of the prostate.

L'hyperplasie bénigne de la prostate est l'une des maladies les plus fréquentes de l'homme âgé et est la principale cause de symptômes du bas appareil urinaire. Depuis des décennies, le gold standard des traitements chirurgicaux pour soulager les symptômes du bas appareil urinaire, dus à l'hyperplasie bénigne de la prostate, est la résection transurétrale de la prostate. De nouvelles techniques mini-invasives se sont développées dans le but de réduire la morbidité ou de pouvoir prendre en charge des volumes prostatiques plus importants par voie endoscopique. Nous résumons dans cet article les différentes alternatives chirurgicales à la résection transurétrale de la prostate.

3-Year results following treatment with the second generation of the temporary implantable nitinol device in men with LUTS secondary to benign prostatic obstruction.

BACKGROUND: To report the 3-year results of a prospective, single arm, multicenter, international clinical study with the second generation of the temporary implantable nitinol device (iTIND; Medi-Tate Ltd®, Israel) on men suffering lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). METHODS: Eighty-one men with symptomatic BPO (IPSS ≥ 10, peak urinary flow <12 ml/s, and prostate volume <75 ml) were enrolled in this study between December 2014 and December 2016. Subjects were washed-out 1 month for alpha-blockers and 6 months for 5-ARIs. The implantation was performed under light sedation and the removal 5-7 days later with topical anesthesia. Perioperative results including OR-time, pain (VAS) postoperative complications (Clavien-Dindo-Grading System), functional results (Qmax, IPSS, PVR) and quality of life (QoL) were assessed at 1, 3, 6 months, 1, 2, and 3 years. Sexual and ejaculatory function were evaluated using two yes/no questions. RESULTS: Thirty-six month functional results were available for 50 patients and demonstrated that iTIND efficacy remained stable through 3 years, with averages IPSS, QOL, Qmax and PVR of 8.55 + 6.38, 1.76 + 1.32, 15.2 + 6.59 ml/s and 9.38 + 17.4 ml, improved from baseline by -58.2, -55.6, +114.7, and -85.4% (all significantly different from their corresponding baseline values, p < 0.0001). Even considering the Intention to Treat analysis (ITT), the 36-month results confirmed significant improvements of the functional outcomes if compared with baselines values (all p < 0.0001). No late post-operative complications were observed between 12 and 36 months. Sexual function was stable through 3 years, with no reports of sexual or ejaculatory dysfunctions. No patients underwent alternative treatments between 24 and 36 months. CONCLUSION: Treatment of BPO-related LUTS with iTIND demonstrated a significant and durable reduction in symptoms and improvement of functional parameters and quality of life at 3 years of follow-up. No late post-operative complications, ejaculatory dysfunction or additional treatment failures were observed between 24 and 36 months.

Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry.

BACKGROUND: Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. OBJECTIVE: Early-medium-term cancer control and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5-36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. INTERVENTION: Focal cryoablation of MR-visible tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. RESULTS AND LIMITATIONS: A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7yr (IQR 64.9-73.8) and preoperative PSA 10.8ng/ml (IQR 7.8-15.6). Overall FFS at 3yr was 90.5% [95% confidence interval (CI) 84.2-97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4-100) in high risk and 93.3% (95% CI 86.8-100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. CONCLUSIONS: Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. PATIENT SUMMARY: In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

Salvage Lymph Node Dissection for Nodal Recurrent Prostate Cancer: A Systematic Review.

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.

Are clinical guidelines designed according to guidelines? Cross-sectional assessment of quality and transparency of clinical guidelines in urology.

PURPOSE: Guidelines and recommendations become increasingly important in clinical urologic practice. This study aims to inform clinicians using guidelines on how to evaluate the quality of the methodology and transparency of these documents. METHODS: The guidelines on management of castration-resistant prostate cancer of the American Urology Association, European Association of Urology, National Comprehensive Cancer Network, National Institute for Health and Care Excellence, European Society of Medical Oncology were reviewed using the AGREE-II tool (Appraisal of Guidelines for Research and Evaluation). We reported and compared the domain scores for the domains 1 scope and purpose, 2 stakeholder involvement, 3 rigor of development, 4 clarity of presentation, 5 applicability, and 6 editorial independence (100% indicates highest-best quality score). RESULTS: The domains evaluated highest and with lowest variability were 'editorial independence' (92% {88-95%}) and 'clarity of presentation' (83% {72-90%}), while the domains with the lowest scores and most variability were 'stakeholder involvement' (56% {36-79%}) and 'applicability' (40% {30-63%}). Length and extent of detail of guidelines vary considerably, each with its own strengths and limitations and adapted to target users. Standard external review using AGREE criteria may be preferable. A formal search strategy was not performed. Findings may be outdated by guidelines' updates. CONCLUSIONS: Clinicians using practice guidelines need to be aware of the different domains of methodology and transparency used to assess the quality of guidelines contents and recommendations. Urologists increasingly use guidelines for support in evidence-based recommendations in clinical practice. It is very important to know how to assess these documents. This study applies standard criteria to compare the design and background of different available guidelines on prostate cancer no longer responding to hormonal treatment.

New technologies and techniques for prostate cancer focal therapy.

INTRODUCTION: The aim of this study was to review the oncological and functional outcomes of new and established primary focal treatments (FT) for localized prostate cancer (PCa). EVIDENCE ACQUISITION: We performed a systematic search of published studies on FT for localized PCa using electronic databases (Medline and Embase). These studies included reports on hemi-ablation, focal ablation and target-ablation. We excluded salvage focal therapy studies and limited the search to those with a minimum of 12 months of follow-up. EVIDENCE SYNTHESIS: We selected 20 studies with a total of 2523 patients who were treated in the primary setting. The energy sources used were cryotherapy (8), high-intensity focused ultrasound (9), irreversible electroporation (1), photodynamic therapy (1) and focused laser ablation (1), with 65% hemiablation, 25% focal ablation and 10% target-ablation. The median follow-ups ranged from 6 to 44.4 months. Mean age was 60.4-70 years and mean prostate-specific antigen was 4.4-<10 ng/dL; 26-100% had a Gleason Score of 6, and 0-65% had a Gleason Score of 7. Patient selection was carried out by TRUS biopsy in 9 studies, while transperineal template mapping biopsy and mp-MRI were employed in six and 13 studies, respectively. The overall post-treatment positive biopsy rate was 1.2-51% with 1.6-32% patients having a residual disease in the treated area. The post-treatment continence rates were 90-100%, and the rates of erectile dysfunction ranged from 0-53.2%. CONCLUSIONS: Reliable evidence for the partial-gland treatment of PCa is increasing, and encouraging mid-term oncologic outcomes with the preservation of sexual and urinary functions have been reported. Accurate patient selection at the outset of treatment and careful follow-up seem key attributes to achieve excellent functional results and encouraging oncological outcomes.

Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients.

PURPOSE: Treatments with cancer vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T cells in the bladder and tumor-regression in murine bladder cancer models. Here, we determined whether an adjuvanted cancer vaccine can be safely administered with concomitant standard intravesical Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle-invasive bladder cancer (NMIBC). EXPERIMENTAL DESIGN: In a nonrandomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine injections or BCG instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG instillations. RESULTS: The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T cells were induced in blood, irrespective of BCG treatment. Interestingly, such T cells were only detected in urine upon BCG-induced T-cell infiltration. CONCLUSIONS: Cancer vaccines, including strong adjuvants, can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T cells in the bladder upon BCG provides proof-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717-25. ©2016 AACR.

New and Established Technology in Focal Ablation of the Prostate: A Systematic Review.

CONTEXT: Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments. OBJECTIVE: To summarize the evidence regarding sources of energy employed in focal therapy. EVIDENCE ACQUISITION: Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations. EVIDENCE SYNTHESIS: Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity. CONCLUSIONS: Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care. PATIENT SUMMARY: Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.

[Focal therapy in prostate cancer: rationale, results and perspectives]. / Thérapie focale du cancer de la prostate: rationnel, résultats et perspectives.

Focal therapy is a novel treatment strategy in prostate cancer aiming to treat only the area of the gland harbouring clinically significant disease. The overall objective is to maintain the oncological benefit of active treatment while minimising treatment-related morbidity. Leading centres are currently evaluating various minimally invasive technologies in a rigorous manner. Oncological and functional results in mid-term are encouraging with low rate of urinary incontinence and erectile dysfunction. However, the oncological outcome needs to be evaluated in the long-term in the light of the prolonged natural history of the disease.