NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Negative mpMRI Rules Out Extra-Prostatic Extension in Prostate Cancer before Robot-Assisted Radical Prostatectomy.

Background: The accuracy of multi-parametric MRI (mpMRI) in the pre-operative staging of prostate cancer (PCa) remains controversial. Objective: The purpose of this study was to evaluate the ability of mpMRI to accurately predict PCa extra-prostatic extension (EPE) on a side-specific basis using a risk-stratified 5-point Likert scale. This study also aimed to assess the influence of mpMRI scan quality on diagnostic accuracy. Patients and Methods: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre. Three radiologists retrospectively reviewed mpMRI blinded to RP pathology and assigned a Likert score (1-5) for EPE on each side of the prostate. Each scan was also ascribed a Prostate Imaging Quality (PI-QUAL) score for assessing the quality of the mpMRI scan, where 1 represents the poorest and 5 represents the best diagnostic quality. Outcome measurements and statistical analyses: Diagnostic performance is presented for the binary classification of EPE, including 95% confidence intervals and the area under the receiver operating characteristic curve (AUC). Results: A total of 231 lobes from 121 men (mean age 56.9 years) were evaluated. Of these, 39 men (32.2%), or 43 lobes (18.6%), had EPE. A Likert score ≥3 had a sensitivity (SE), specificity (SP), NPV, and PPV of 90.4%, 52.3%, 96%, and 29.9%, respectively, and the AUC was 0.82 (95% CI: 0.77-0.86). The AUC was 0.76 (95% CI: 0.64-0.88), 0.78 (0.72-0.84), and 0.92 (0.88-0.96) for biparametric scans, PI-QUAL 1-3, and PI-QUAL 4-5 scans, respectively. Conclusions: MRI can be used effectively by genitourinary radiologists to rule out EPE and help inform surgical planning for men undergoing RARP. EPE prediction was more reliable when the MRI scan was (a) multi-parametric and (b) of a higher image quality according to the PI-QUAL scoring system.

Intraoperative Frozen Section for Margin Evaluation During Radical Prostatectomy: A Systematic Review.

CONTEXT: Surgical margin status and preservation of the neurovascular bundles (NVB) are important prognostic indicators for oncological and functional outcomes of patients undergoing radical prostatectomy (RP). Intraoperative frozen section (IFS) has been used to evaluate margin status during surgery with the intention of reducing positive surgical margins (PSMs) and guiding safe preservation of the NVBs during RP, but its value is controversial. OBJECTIVE: To evaluate current literature comparing outcomes of men undergoing RP with IFS versus RP without IFS. EVIDENCE ACQUISITION: Medline, Embase, and Cochrane Library searches for all relevant publications (PROSPERO ID CRD42019125940), including comparative studies reporting on men undergoing RP with and without IFS, were performed. Outcomes of interest were surgical margin status, long-term oncological outcomes, NVB status, and erectile function (EF) recovery. Data were narratively synthesised in light of methodological and clinical heterogeneity of included studies. EVIDENCE SYNTHESIS: After screening 834 publications, 10 nonrandomised retrospective comparative studies (including 16 897 patients) were retrieved. The technique of IFS differed considerably between studies. Eight studies reported a reduction in PSM rates (-1.4% to -14.5%) with IFS, though two studies report higher PSM rates (+0.4% and +10%) with IFS. Three studies reported on long-term oncological outcomes, and no difference was seen with IFS. Three studies reported on the performance of IFS systematically at the posterolateral margin of the prostate (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique). In all these three studies, either NVB preservation or EF recovery was improved. All studies were deemed to be at either a serious or a moderate risk of bias. CONCLUSIONS: No randomised controlled trials were identified, and significant heterogeneity existed with regard to many features of the studies included. Within the limitations of this review, the evidence suggests that IFS during RP can facilitate a modest reduction in PSM rates. There is evidence that IFS performed systematically at the posterolateral margin of the prostate can facilitate more NVB preservation. However, in the main, the lack of prospective, randomised, standardised research with long-term oncological and functional outcomes precludes strong conclusions and highlights the need for such studies. PATIENT SUMMARY: The data of this review suggest that frozen section sampling of the prostate (ie, whilst the patient is still asleep) during prostate cancer surgery can reduce the likelihood of cancer being detected at the edge of the removed prostate. It also finds that a type of frozen section analysis (neurovascular structure-adjacent frozen-section examination [NeuroSAFE] technique) can help allow the nerves around the prostate to be left intact safely during surgery. However, the studies in this review are very different from one another and generally at a high risk of errors. Therefore, comparisons and conclusions must be made carefully.

NeuroSAFE robot-assisted laparoscopic prostatectomy versus standard robot-assisted laparoscopic prostatectomy for men with localised prostate cancer (NeuroSAFE PROOF): protocol for a randomised controlled feasibility study.

INTRODUCTION: Robot-assisted laparoscopic prostatectomy (RALP) offers potential cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are spared during a nerve spare (NS) RALP. There is reluctance, however, to perform NS RALP when there are concerns that the cancer extends beyond the capsule of the prostate into the NVB, as NS RALP in this instance increases the risk of a positive surgical margin (PSM). The NeuroSAFE technique involves intraoperative fresh-frozen section analysis of the posterolateral aspect of the prostate margin to assess whether cancer extends beyond the capsule. There is evidence from large observational studies that functional outcomes can be improved and PSM rates reduced when the NeuroSAFE technique is used during RALP. To date, however, there has been no randomised controlled trial (RCT) to substantiate this finding. The NeuroSAFE PROOF feasibility study is designed to assess whether it is feasible to randomise men to NeuroSAFE RALP versus a control arm of 'standard of practice' RALP. METHODS: NeuroSAFE PROOF feasibility study will be a multicentre, single-blinded RCT with patients randomised 1:1 to either NeuroSAFE RALP (intervention) or standard RALP (control). Treatment allocation will occur after trial entry and consent. The primary outcome will be assessed as the successful accrual of 50 men at three sites over 15 months. Secondary outcomes will be used to aid subsequent power calculations for the definitive full-scale RCT and will include rates of NS; PSM; biochemical recurrence; adjuvant treatments; and patient-reported functional outcomes on potency, continence and quality of life. ETHICS AND DISSEMINATION: NeuroSAFE PROOF has ethical approval (Regional Ethics Committee reference 17/LO/1978). NeuroSAFE PROOF is supported by National Institute for Healthcare Research Research for Patient Benefit funding (NIHR reference PB-PG-1216-20013). Findings will be made available through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03317990.

Early surgical outcomes and oncological results of robot-assisted partial nephrectomy: a multicentre study.

OBJECTIVE: To describe a multicentre experience of robot-assisted partial nephrectomy (RAPN) in northern England, with focus on early surgical outcomes and oncological results. PATIENTS AND METHODS: All consecutive patients undergoing RAPN at four tertiary referral centres in northern England in the period 2012-2015 were included for analysis. RAPN was performed via a transperitoneal approach using a standardized technique. Prospective data collection was performed to capture preoperative characteristics (including R.E.N.A.L. nephrometry score), and peri-operative and postoperative data, including renal function. Correlations between warm ischaemia time (WIT), positive surgical margin (PSM) rate, complication rates, R.E.N.A.L. nephrometry scores and learning curve were assessed using univariate and multivariate analyses. RESULTS: A total of 250 patients (mean age 58.1 ± 13 years, mean ± sd body mass index 27.3 ± 7 kg/m2 ) were included, with a median (range) follow-up of 12 (3-36) months. The mean ± sd tumour size was 30.6 ± 10 mm, mean R.E.N.A.L. nephrometry score was 6.1 ± 2 and 55% of tumours were left-sided. Mean ± sd operating console time was 141 ± 38 min, WIT 16.7 ± 8 min and estimated blood loss 205 ± 145 mL. There were five conversions (2%) to open/radical nephrectomy. The overall complication rate was 16.4% (Clavien I, 1.6%; Clavien II, 8.8%; Clavien III, 6%; Clavien IV/V; 0%). Pathologically, 82.4% of tumours were malignant and the overall PSM rate was 7.3%. The mean ± sd preoperative and immediate postoperative estimated glomerular filtration rates were 92.8 ± 27 and 80.8 ± 27 mL/min/1.73 m2 , respectively (P = 0.001). In all, 66% of patients remained in the same chronic kidney disease category postoperatively, and none of the patients required dialysis during the study period. 'Trifecta' (defined as WIT < 25 min, negative surgical margin status and no peri-operative complications) was achieved in 68.4% of patients overall, but improved with surgeon experience. PSM status and long WIT were significantly associated with early learning curve. CONCLUSION: This is the largest multicentre RAPN study in the UK. Initial results show that RAPN is safe and can be performed with minimal morbidity. Early oncological outcomes and renal function preservation data are encouraging.

A case of laparoscopic ureteric reimplantation in a solitary urinary system.

Ureteric strictures can be caused by traumatic pelvic surgery, urolithiasis and instrumentation. There are various treatment options for ureteric stricture, including laparoscopic ureteric reimplantation. A 56-year-old female with a history of chronic left pelviureteric junction obstruction presented with urosepsis secondary to right-sided urolithiasis. The patient had a left nephrectomy and developed right-sided ureteric stricture following repeated ureteroscopy to manage her stone disease. The treatment with ureteric stenting was unsuccessful. Here we present a case on the feasibility of laparoscopic reimplantation for ureteric stricture in a solitary kidney to preserve renal function and avoid further ureteroscopy or nephrostomies.

Diethylstilboestrol for the treatment of prostate cancer: past, present and future.

The aim of this review was to discuss the most recent data from current trials of diethylstilboestrol (DES) to identify its present role in advanced prostate cancer treatment as new hormonal therapies emerge. The most relevant clinical studies using DES in castration-refractory prostate cancer (CRPC) were identified from the literature. The safety, efficacy, outcomes and mechanisms of action are summarized. In the age of chemotherapy this review highlights the efficacy of oestrogen therapy in CRPC. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

Bladder neck sparing in radical prostatectomy.

The role of a bladder neck sparing (BNS) technique in radical prostatectomy (RP) remains controversial. The potential advantages of improved functional recovery must be weighed against oncological outcomes. We performed a literature review to evaluate the current knowledge regarding oncological and functional outcomes of BNS and bladder neck reconstruction (BNr) in RP. A systematic literature review using on-line medical databases was performed. A total of 33 papers were identified evaluating the use of BNS in open, laparoscopic and robotic-assisted RP. The majority were retrospective case series, with only one prospective, randomised, blinded study identified. The majority of papers reported no significant difference in oncological outcomes using a BNS or BNr technique, regardless of the surgical technique employed. Quoted positive surgical margin rates ranged from 6% to 32%. Early urinary continence (UC) rates were ranged from 36% to 100% at 1 month, with long-term UC rate reported at 84-100% at 12 months if the bladder neck (BN) was spared. BNS has been shown to improve early return of UC and long-term UC without compromising oncological outcomes. Anastomotic stricture rate is also lower when using a BNS technique.

Use of optical dilating trocar for initial access during extraperitoneal laparoscopic radical prostatectomy.

BACKGROUND AND PURPOSE: For fully extraperitoneal laparoscopic radical prostatectomy, open port placement is standard. This takes quite some time, so with the availability of trocars that combine optical control and radial dilation, an easier and faster technique was tested. PATIENTS AND METHODS: In 70 consecutive cases, preperitoneal space creation was attempted with only a 1-cm skin incision, developing further access using an optical dilating trocar with a laparoscope. Open preparation of the subcutaneous fat and incision of the anterior rectus fascia was not necessary. RESULTS: Access was successful on the first attempt in 67 cases. The time from the first skin incision to an established preperitoneal space was <10 minutes. CONCLUSIONS: We believe this technique offers an easier, faster, and safe way to introduce the first port for extraperitoneal laparoscopic radical prostatectomy.

Ureteric embolization: an alternative treatment strategy for urinary fistulae complicating advanced pelvic malignancy.

OBJECTIVE: To report experience with a minimally invasive technique for palliation of urinary fistula/incontinence complicating advanced pelvic malignancy or its treatment. PATIENTS AND METHODS: We used ureteric embolization with permanent nephrostomy drainage in eight renal units in five patients for palliation of symptoms. All procedures were done under local anaesthesia as day-case procedures. Nephrostomy tubes were changed at regular intervals on an outpatient basis. Embolization was repeated when required. RESULTS: The follow-up was 2-84 months; four patients died from the underlying malignancy during the follow-up. All patients were continent and had effective palliation of their symptoms. Two patients required repeat embolization. There were no embolization-related complications. CONCLUSIONS: Ureteric embolization is a safe and effective minimally invasive palliative treatment option in urinary fistulae or incontinence complicating advanced pelvic malignancy.