Kidney-sparing surgery has equivalent oncological outcomes to radical nephroureterectomy for ureteral urothelial carcinoma.

INTRODUCTION AND OBJECTIVE: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large prospective international UTUC registry. METHODS: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included UTUC patients who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumour features' differences between groups. RESULTS: Of 391 patients with ureteral UTUC, 309 (79.0%) received RNU, and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n=28) or segmental resection (n=54). After PSM, there were no differences in OS (p=0.525), CSS (p=0.487), upper tract RFS (p=0.147), intravesical RFS (p=0.989), PFS (p=0.617), and MFS (p=0.336) between KSS and RNU. Both ureteroscopic ablation and segmental resection had similar OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumour locations following segmental resection. CONCLUSIONS: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumour locations following segmental resection.

Lasers in Transurethral Enucleation of the Prostate-Do We Really Need Them.

The acronym EEP, coding for transurethral Endoscopic Enucleation of the Prostate, was introduced in 2016 by the European Association of Urology (EAU) guidelines panel on management of non-neurogenic male lower urinary tract symptoms (LUTS) and benign prostatic obstruction (BPO). Since then, a laser-based treatment, Holmium Laser Enucleation of the Prostate (HoLEP), and the current-based treatment of bipolar enucleation of the prostate (BipoLEP) are equally appreciated as valuable options for the management of benign prostatic obstruction (BPO). This was mainly inspired by the results of two meta-analyses on randomized controlled trials, comparing open prostatectomy with either Holmium Laser Enucleation of the Prostate (HoLEP) or bipolar enucleation of the prostate (BipoLEP). Prior to that, HoLEP was embraced as the only valid option for transurethral enucleation, although evidence for equivalence existed as early as 2006, but was not recognized due to a plethora of acronyms for bipolar energy-based treatments and practiced HoLEP-centrism. On the other hand, the academic discourse focused on different (other) laser approaches that came up, led by Thulium:Yttrium-Aluminum-Garnet (Tm:YAG) Vapoenucleation (ThuVEP) in 2009 and, finally, transurethral anatomical enucleation with Tm:YAG support (thulium laser enucleation of the prostate, ThuLEP) in 2010. Initially, the discourse on lasers focused on the different properties of lasers rather than technique or surgical anatomy, respectively. In and after 2016, the discussion ultimately moved towards surgical technique and accepting anatomical preparation as the common of all EEP techniques (AEEP). Since then, the unspoken question has been raised, whether lasers are still necessary to perform EEP in light of existing evidence, given the total cost of ownership (TCO) for these generators. This article weighs the current evidence and comes to the conclusion that no evidence of superiority of one modality over another exists with regard to any endpoint. Therefore, in the sense of critical importance, AEEP can be safely and effectively performed without laser technologies and without compromise.

Confocal Laser Endomicroscopy and Optical Coherence Tomography for the Diagnosis of Prostate Cancer: A Needle-Based, In Vivo Feasibility Study Protocol (IDEAL Phase 2A).

BACKGROUND: Focal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information. OBJECTIVE: This study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology. METHODS: In this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy- and optical coherence tomography-based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage 2a recommendations. RESULTS: At present, the study is enrolling patients and results and outcomes are expected in 2019. CONCLUSIONS: Confocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03253458; https://clinicaltrials.gov/ct2/show/NCT03253458 (Archived by WebCite at http://www.webcitation.org/6z9owM66B). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9813.

Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies.

BACKGROUND: Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. OBJECTIVE: The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. METHODS: In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. RESULTS: Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. CONCLUSIONS: For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. TRIAL REGISTRATION: Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central Committee on Research Involving Human Subjects NL55537.018.15; https://www.toetsingonline.nl /to/ccmo_search.nsf/fABRpop?readform&unids=6B72AE6EB0FC3C2FC125821F001B45C6 (Archived by WebCite at http://www.webcitation.org/6wwJQvqWh). Confocal Laser Endomicroscopy in the upper urinary tract: ClinicalTrials.gov NCT03013920; https://clinicaltrials.gov/ct2/show/NCT03013920? term=NCT03013920&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPkjyt0); and Dutch Central Committee on Research Involving Human Subjects NL52989.018.16; https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C).

Comparison of retropubic, laparoscopic and robotic radical prostatectomy: who is the winner?

PURPOSE: This study is a systematic analysis of the evidence regarding oncological, perioperative and postoperative outcomes and the cost of open retropubic radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: Summary data was abstracted from 104 original research articles representing 227,400 patients. PubMed/Medline, Scopus, Google Scholar, EMBASE and the Cochrane Library were reviewed in December 2016. A total of 104 publications were selected for inclusion. The primary outcomes were positive surgical margin (PSM) and major complication rate according to Clavien classifications. Secondary outcomes were operative time, length of hospital stay, estimated blood loss, transfusions, conversions, rate of post-operative erectile dysfunction and incontinence and total cost of procedure. RESULTS: ORP had a significantly higher rate than RALP for PSM (OR: 1.18; 95% CI 1.05-1.32; p = 0.004), but the rate of PSM was not significantly different between ORP versus LRP (OR: 1.37; 95% CI 0.88-2.14; p = 0.17) and RALP versus LRP (OR: 0.83; 95% CI 0.40-1.72; p = 0.62). The major Clavien complication rate was significantly different between ORP and RALP (OR: 2.14; 95% CI 1.24-3.68; p = 0.006). Estimated blood loss, transfusions and length of hospital stay were low for RALP, moderate for LRP and high for ORP. The rate of erectile dysfunction (OR: 2.58; 95% CI 1.77-3.75; p < 0.001) and incontinence (OR: 3.57; 95% CI 2.28-5.58; p < 0.001) were significantly lower after RALP than LRP and equivalent for other comparisons. Total cost was highest for RALP, followed by LRP and ORP. CONCLUSIONS: For PSM and peri- and post-operative complications, RALP showed better results than ORP and LRP. In the context of the biases between the studies, one should interpret the results with caution.

Outcome from 5-year live surgical demonstrations in urinary stone treatment: are outcomes compromised?

PURPOSE: To compare intra- and post-operative outcomes of endourological live surgical demonstrations (LSDs) and routine surgical practice (RSP) for urinary stones. METHODS: Consecutive ureterorenoscopic (URS) and percutaneous (PNL) urinary stone procedures over a 5-year period were reviewed. Procedures were divided into LSDs and RSP. Differences between the groups were separately analysed for URS and PNL. Primary outcomes included intra- and post-operative complication rates and grades. Secondary outcomes were operation time, length of hospital stay, stone-free rate, and retreatment rate. Pearson's Chi-square analysis, Mann-Whitney U test, and logistic and linear regression were used to compare outcomes between LSDs and RSP. RESULTS: During the study period, we performed 666 URSs and 182 PNLs, and 151 of these procedures were LSDs. Among URSs, the overall intra-operative complication rate was 3.2% for LSDs and 2.5% for RSP (p = 0.72) and the overall post-operative complication rate was 13.7% for LSDs and 8.8% for RSP (p = 0.13). Among PNLs, the overall intra-operative complication rate was 8.9% for LSDs and 5.6% for RSP (p = 0.52) and the overall post-operative complication rate was 28.6% for LSDs and 34.9% for RSP (p = 0.40). For both URSs and PNLs, no statistically significant differences in complication grade scores were observed between LSDs and RSP. Operation time was significantly longer for LSD-URS group, but there was no difference between the PNL groups. There were no significant differences in length of hospital stay and stone-free rate. The retreatment rate was higher in the LSD-URS group compared with RSP-URS group but similar between the PNL groups. Multiple logistic regression analyses, adjusting for confounders, revealed no association between LSD and more or less favourable outcomes as compared to RSP. CONCLUSION: Live surgical demonstrations do not seem to compromise patients' safety and outcomes when performed by specialised endourologists.

Irreversible Electroporation for the Ablation of Renal Cell Carcinoma: A Prospective, Human, In Vivo Study Protocol (IDEAL Phase 2b).

BACKGROUND: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality. OBJECTIVE: The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumors. This study conforms to the recommendations of the IDEAL Collaboration and can be categorized as a phase 2B exploration trial. METHODS: In this prospective clinical trial, IRE will be performed in 20 patients aged 18 years and older presenting with a solid enhancing small renal mass (SRM) (≤4 cm) who are candidates for ablation. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) will be performed at 1 day pre-IRE, and 1 week post-IRE. Computed tomography (CT), CEUS, and MRI will be performed at 3 months, 6 months, and 12 months post-IRE. RESULTS: Presently, recruitment of patients has started and the first inclusions are completed. Preliminary results and outcomes are expected in 2018. CONCLUSIONS: To establish the position of IRE ablation for treating renal tumors, a structured stepwise assessment in clinical practice is required. This study will offer fundamental knowledge on the clinical efficacy of IRE ablation for SRMs, potentially positioning IRE as ablative modality for renal tumors and accrediting future research with long-term follow-up. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02828709; https://clinicaltrials.gov/ct2/show/NCT02828709 (archived by WebCite at http://www.webcitation.org/6nmWK7Uu9). Dutch Central Committee on Research Involving Human Subjects NL56935.018.16.

Ultrasound-contrast-agent dispersion and velocity imaging for prostate cancer localization.

Prostate cancer (PCa) is the second-leading cause of cancer death in men; however, reliable tools for detection and localization are still lacking. Dynamic Contrast Enhanced UltraSound (DCE-US) is a diagnostic tool that is suitable for analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods for the analysis of the bolus convective dispersion process have shown promise to localize angiogenesis. However, independent estimation of dispersion was not possible due to the ambiguity between convection and dispersion. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified. To this end, model-based parameter estimation is employed, that permits extraction of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. Clinical evaluation using data recorded from 25 patients shows that the proposed method can be applied effectively to DCE-US, and is able to locally characterize the hemodynamics, yielding promising results (receiver-operating-characteristic curve area of 0.84) for prostate cancer localization.

Irreversible electroporation: state of the art.

The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate.

Is photodynamic diagnosis ready for introduction in urological clinical practice?

The aim of this review is to provide an up-to-date review of the available literature on photodynamic diagnosis (PDD) for nonmuscle-invasive bladder cancer, to present the technique in a comprehensive approach and, finally, to discuss the relevance of PDD in clinical practice in terms of indications, outcomes and its development trend. A literature search was conducted up to July 2012, using MEDLINE and EMBASE via Ovid databases to identify published studies on PDD for nonmuscle-invasive bladder cancer. Only English-language and human-based full manuscripts that reported on case series and studies with >40 participants, concerning clinical evidence of the technique, its efficacy and safety data were included. Evidence showed that PDD significantly improves detection of bladder cancer compared with standard white-light cystoscopy, having proven to be more effective for the diagnosis of carcinoma in situ. This condition seems to facilitate more complete resections, resulting in a lower residual tumor rate, which, in turn consecutively leads to higher recurrence-free survival rates. The literature search demonstrated that for mid- and long-term follow-up, PDD showed acceptable outcomes in terms of tumor detection, as well as lower residual tumor and lower recurrence rates compared with white-light cystoscopy. It has proven to be safe and well tolerated; the major limitations of PDD are its low specificity and elevated costs.

Follow-up procedures for non-muscle-invasive bladder cancer: an update.

Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients present with a disease that is confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1). The stratification of patients to low-, intermediate- and high-risk groups represents the cornerstone for the indication of adjuvant and follow-up treatment. Owing to the high recurrence rate of bladder tumors, a surveillance protocol is recommended to all patients. Currently, the combination of cystoscopy, imaging and urinary cytology represent the follow-up. A systematic review of the recent English literature on follow-up procedures of non-muscle-invasive bladder cancer is performed. The authors review the existing follow-up procedures, with a focus on novel molecular-targeted approaches. At the present time, the additional use and utility of urine-based molecular markers in the follow-up of patients remains unclear and we have to rely on cystoscopic evaluation adapted to risk group classification.