Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.

AIMS: Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP. METHODS AND RESULTS: Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not. CONCLUSIONS: Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.

NeuroSAFE in radical prostatectomy increases the rate of nerve-sparing surgery without affecting oncological outcome.

OBJECTIVES: To investigate the impact of intra-operative neurovascular structure-adjacent frozen-section examination (NeuroSAFE) on the rate of nerve-sparing surgery (NSS) and oncological outcome in a large radical prostatectomy (RP) cohort. PATIENTS AND METHODS: Between January 2016 and December 2020, 1756 prostate cancer patients underwent robot-assisted RP, of whom 959 (55%) underwent this with NeuroSAFE and 797 (45%) without (control cohort). In cases where NeuroSAFE showed tumour in the margin, a secondary resection was performed. The effect of NeuroSAFE on NSS and positive surgical margin (PSM) status was analysed using logistic regression. Cox regression was used to identify predictors of biochemical recurrence-free survival (BCRFS). RESULTS AND LIMITATIONS: Patients in the NeuroSAFE cohort had a higher tumour grade (P < 0.001) and clinical stage (P < 0.001) than those in the control cohort. NeuroSAFE enabled more frequent NSS for both pT2 (93% vs 76%; P < 0.001) and pT3 disease (83% vs 55%; P < 0.001). In adjusted analysis, NeuroSAFE resulted in more frequent unilateral (odds ratio [OR] 3.90, 95% confidence interval (CI) 2.90-5.30; P < 0.001) and bilateral (OR 5.22, 95% CI 3.90-6.98; P < 0.001) NSS. While the PSM rate decreased from 51% to 42% in patients with pT3 stage disease (P = 0.031), NeuroSAFE was not an independent predictor of PSM status (OR 0.85, 95% CI 0.68-1.06; P = 0.2) in the entire cohort. Patients who underwent NeuroSAFE had better BCRFS compared to the control cohort (hazard ratio 0.62, 95% CI 0.45-0.84; P = 0.002). This study is limited by its comparison with a historical cohort and lack of functional outcomes. CONCLUSIONS: NeuroSAFE enables more unilateral and bilateral NSS without negatively affecting surgical margin status and biochemical recurrence. This validation study provides a comprehensive overview of the implementation, evaluation and intra-operative decision making associated with NeuroSAFE in clinical practice.

Percentage Gleason pattern 4 and PI-RADS score predict upgrading in biopsy Grade Group 2 prostate cancer patients without cribriform pattern.

PURPOSE: To identify parameters to predict upgrading in biopsy Grade Group (GG) 2 prostate cancer patients without cribriform and intraductal carcinoma (CR/IDC) on biopsy. METHODS: Preoperative biopsies from 657 men undergoing radical prostatectomy (RP) for prostate cancer were reviewed for GG, presence of CR/IDC, percentage Gleason pattern 4, and tumor length. In men with biopsy GG2 without CR/IDC (n = 196), clinicopathologic features were compared between those with GG1 or GG2 without CR/IDC on RP (GG ≤ 2-) and those with GG2 with CR/IDC or any GG > 2 (GG ≥ 2+). Logistic regression analysis was used to predict upgrading in the biopsy cohort. RESULTS: In total 283 men had biopsy GG2 of whom 87 (30.7%) had CR/IDC and 196 (69.3%) did not. CR/IDC status in matched biopsy and RP specimens was concordant in 179 (63.3%) and discordant in 79 (27.9%) cases (sensitivity 45.1%; specificity 92.6%). Of 196 biopsy GG2 men without CR/IDC, 106 (54.1%) had GG ≥ 2+ on RP. Multivariable logistic regression analysis showed that age [odds ratio (OR): 1.85, 95% confidence interval (CI)1.09-3.20; p = 0.025], percentage Gleason pattern 4 (OR 1.54, 95% CI 1.17-2.07; p = 0.003), PI-RADS 5 lesion (OR 2.17, 95% CI 1.03-4.70; p = 0.045) and clinical stage T3 (OR 3.60; 95% CI 1.08-14.50; p = 0.049) were independent parameters to predict upgrading to GG ≥ 2+ on RP in these men. CONCLUSIONS: Age, clinical stage T3, percentage Gleason pattern 4 and presence of PI-RADS 5 lesions are independent predictors for upgrading in men with biopsy GG2 without CR/IDC. These findings allow for improved clinical decision-making on surveillance eligibility in intermediate-risk prostate cancer patients.

Intraoperative assessment and reporting of radical prostatectomy specimens to guide nerve-sparing surgery in prostate cancer patients (NeuroSAFE).

AIMS: Radical prostatectomy for prostate cancer is frequently complicated by urinary incontinence and erectile dysfunction. Nerve-sparing surgery reduces the risk of postoperative complications and can be optimised by the use of intraoperative frozen sections of the adjacent neurovascular structure (NeuroSAFE). The aims of this study were to evaluate the pathological outcomes of the NeuroSAFE technique and to develop a comprehensive algorithm for intraoperative clinical decision-making. METHODS AND RESULTS: Between September 2018 and May 2019, 491 NeuroSAFE procedures were performed in 258 patients undergoing radical prostatectomy; 74 of 491 (15.1%) NeuroSAFE specimens had positive surgical margins. As compared with the corresponding paraffin sections, NeuroSAFE had a positive predictive value and negative predictive value of 85.1% and 95.4%, respectively. In 72.2% of secondary neurovascular bundle resections prompted by a NeuroSAFE positive surgical margin, no tumour was present. These cases more often had a positive surgical margin of ≤1 mm (48.7% versus 20.0%; P = 0.001) and only one positive slide (69.2% versus 33.3%; P = 0.008). None of the nine patients with Gleason pattern 3 at the surgical margin, a positive surgical margin length of ≤1 mm and one positive slide had tumour in the secondary resection. CONCLUSIONS: This study provides a systematic reporting template for pathological intraoperative NeuroSAFE evaluation, supporting intraoperative clinical decision-making and comparison between prostate cancer operation centres.

Expanding utilization of robotic partial nephrectomy for clinical T1b and complex T1a renal masses.

INTRODUCTION: Partial nephrectomy is the standard of care for cT1a renal masses, offering equivalent oncologic outcomes and lower renal function impairment when compared to radical nephrectomy, with excellent overall survival results. Robot-assisted partial nephrectomy (RAPN) allows to perform a precise tumor excision, simplifying the reconstruction steps of the procedure, especially in the treatment of complex or large renal tumors. Aim of this study was to summarize the available perioperative, functional, and oncological outcomes of RAPN performed for complex and/or large (cT1b) renal cell carcinoma (RCC). MATERIALS AND METHODS: We performed a nonsystematic review of the literature using a free-text protocol in the Medline database, using the terms "robot-assisted partial nephrectomy" and "robotic partial nephrectomy." Two Authors reviewed separately to select RAPN series reporting data about complex and cT1b RCC. Other significant studies cited in the reference lists of the selected papers were also evaluated. EVIDENCE SYNTHESIS: According to the currently available evidences, RAPN offers promising results in terms of perioperative, functional, and oncological outcomes for the conservative management of complex or large renal tumors, even when compared with open and laparoscopic partial nephrectomy. Robot-assisted procedure allows surgeons to treat large and challenging renal masses, even if with higher warm ischemia time, operating time, and estimated blood loss in comparison with those obtained for the treatment of smaller lesions. CONCLUSIONS: In the hands of experienced surgeons, RAPN is a safe and reproducible approach for the treatment of cT1b and more challenging renal tumors, and could represent the way to expand the indications for minimally invasive conservative approach to RCC.

Urinary Incontinence and Sexual Function After the Introduction of NeuroSAFE in Radical Prostatectomy for Prostate Cancer.

BACKGROUND: Nerve-sparing (NS) radical prostatectomy (RP) results in better functional outcomes. Intraoperative neurovascular structure-adjacent frozen section examination (NeuroSAFE) significantly increases the frequency of NS surgery. The effect of NeuroSAFE on postoperative erectile function (EF) and continence is not yet clear. OBJECTIVE: To describe EF and continence outcomes for men undergoing RP with the NeuroSAFE technique. DESIGN, SETTING, AND PARTICIPANTS: Between September 2018 and February 2021, 1034 men underwent robot-assisted RP. Data for patient-reported outcomes were collected via validated questionnaires. INTERVENTION: NeuroSAFE technique for RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Continence was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) or Expanded Prostate Cancer Index Composite short form (EPIC-26) and defined as use of 0-1 pads/d. EF was evaluated using EPIC-26 or the International Index of Erectile Function short form (IIEF-5), with data converted according to the Vertosick method and categorized. Descriptive statistics were used to asses and describe tumor characteristics and continence and EF outcomes. RESULTS AND LIMITATIONS: Of the 1034 men who underwent RP after introduction of the NeuroSAFE technique, 63% and 60% completed a preoperative and at least one postoperative questionnaire on continence and EF, respectively. Of the men who underwent unilateral or bilateral NS surgery, use of 0-1 pads/d was reported by 93% after 1 yr and 96% after 2 yr; the corresponding rates for men who underwent non-NS surgery were 86% and 78%. Overall, use of 0-1 pads/d was reported by 92% of the men at 1 yr and by 94% at 2 yr after RP. Men in the NS group had a good or intermediate Vertosick score after RP more often than the non-NS group. Overall, 44% of the men had a good or intermediate Vertosick score at 1 and 2 yr after RP. CONCLUSIONS: After introduction of the NeuroSAFE technique, the continence rate was 92% at 1 yr and 94% at 2 yr after RP. The NS group had a greater percentage of men with an intermediate or good Vertosick score and a higher continence rate after RP in comparison to the non-NS group. PATIENT SUMMARY: Our study shows that after introduction of the NeuroSAFE technique during removal of the prostate, the continence rate among patients was 92% at 1 year and 94% at 2 years after surgery. Some 44% of the men had a good or intermediate score for erectile function 1 and 2 years after surgery.

Near-infrared fluorescence imaging: emerging applications in robotic upper urinary tract surgery.

BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a technology with emerging applications in urologic surgery. OBJECTIVE: To describe surgical techniques and provide clinical outcomes for robotic partial nephrectomy (RPN) with selective clamping and robotic upper urinary tract reconstruction featuring novel applications of NIRF imaging. DESIGN, SETTING, AND PARTICIPANTS: Data from 90 patients who underwent successful RPN with selective clamping or upper urinary tract reconstruction utilizing NIRF imaging between April 2011 and October 2012 were reviewed. SURGICAL PROCEDURE: We performed RPN utilizing NIRF imaging to aid with selective clamping and upper tract reconstruction with NIRF imaging, the details of which are outlined in this paper and the accompanying video. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient characteristics, perioperative outcomes, and complications were analyzed. RESULTS AND LIMITATIONS: Of the 48 RPN patients for whom selective clamping was attempted successfully, median estimated blood loss was 200.0 ml, warm ischemia time was 17.0 min, and median change in estimated glomerular filtration rate was -6.3%. There was a 12.5% complication rate, and all complications were Clavien grade 1-3 (14.3%). The upper urinary tract reconstruction utilizing NIRF imaging was performed in 42 patients and included pyelopasty (n=20), ureteral reimplant (n=13), ureterolysis (n=7), and ureteroureterostomy (n=2). Radiographic and symptomatic improvement was observed in 100% of the pyeloplasty, ureteral reimplant, and ureteroureterostomy patients and 71.4% of ureterolysis patients, for an overall success rate of 95.2%. This study is limited by the small sample size, the short follow-up period, and the lack of a comparative cohort. CONCLUSIONS: Our technique of RPN with selective arterial clamping and robotic upper urinary tract reconstruction utilizing NIRF imaging is presented. This technology provides real-time intraoperative angiogram to confirm selective ischemia and may be an adjunct technology to confirm well-perfused tissue within a reconstruction anastomosis. Further investigation is needed to evaluate long-term outcomes of NIRF imaging in robotic upper urinary tract surgery and to delineate its indications.

Robot-assisted sacrocolpopexy for pelvic organ prolapse: surgical technique and outcomes at a single high-volume institution.

BACKGROUND: Pelvic organ prolapse (POP) represents a common female pelvic floor disorder that has a serious impact on quality of life. Several types of procedures with different surgical approaches have been described to correct these defects, but the optimal management is still debated. OBJECTIVE: To describe our surgical technique of robot-assisted sacrocolpopexy (RASC) for POP and to assess its safety and long-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of the medical records of 95 consecutive patients who underwent RASC for POP at our centre from April 2006 to December 2011 was performed. SURGICAL PROCEDURE: RASC with use of polypropylene meshes was performed in all cases using a standardised technique with the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) in a four-arm configuration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical data were collected in a dedicated database. Intraoperative variables, postoperative complications, and outcomes of RASC were assessed. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Median operative time was 101 min. No conversion to open surgery was needed. One vaginal and two bladder injuries occurred and were repaired intraoperatively. Only one Clavien grade 3 postoperative complication was observed (bowel obstruction treated laparoscopically). At a median follow-up of 34 mo, persistent POP was observed in four cases (4.2%). One mesh erosion occurred and required robot-assisted removal of the mesh. Ten (10.5%) patients complained de novo urgency after RASC, which resolved in the first few weeks after surgery. No significant de novo bowel or sexual symptoms were reported. CONCLUSIONS: Our technique of RASC for correction of POP is safe and effective, with limited risk of complications and good long-term results in the treatment of all types of POP. The robotic surgical system facilitates precise and accurate placement of the meshes with short operative time, thereby favouring wider diffusion of minimally invasive treatment of POP. PATIENT SUMMARY: We studied the treatment of patients with vaginal prolapse by using a robot-assisted surgical technique to fix the vaginal wall with a synthetic mesh. This technique was found to be safe and effective, with limited risk of complications and good long-term results.

Posterior muscolofascial reconstruction incorporated into urethrovescical anastomosis during robot-assisted radical prostatectomy.

The rationale of posterior musculofascial plate reconstruction during radical prostatectomy is to shorten the time to reach urinary continence recovery and to reduce the risk of bleeding and anastomosis leakage. We describe our original technique incorporating the posterior muscolofascial reconstruction into urethrovesical anastomosis using robot-assisted radical prostatectomy (RARP). For this reconstructive step, we use a 30-cm V-Loc 90 3-0 barbed suture (V-20 tapered needle). Specifically, the free edge of the posterior layer of the Denonvilliers fascia is approximated to the posterior part of the sphincteric apparatus in a running fashion from left to right. The musculature of the urethral wall is incorporated in this first layer of the running suture. This suture is then continued back to the left in a second layer incorporating the anterior layer of the Denonvilliers fascia (or prostatovesical muscle), the bladder neck, and again the urethra, this time also with urethral mucosa. The urethrovesical anastomosis is completed using a second running barbed suture (15-cm V-Loc 90 3-0 barbed suture, V-20 tapered needle). No intraoperative complications were observed during this step of the procedure. Anastomotic leakages were observed only in 2% of cases. Only 12.5% showed urinary incontinence after catheter removal (1-2 pads). At mean follow-up of 9 months, the urinary continence recovery was 95%, and an anastomosis stricture necessitating an endoscopic incision developed in only three (1.5%) patients. Recent systematic reviews of the literature showed only a minimal advantage in favor of posterior musculofascial reconstruction in terms of urinary continence recovery within 1 month after radical prostatectomy. We support the use of this step of RARP because it is simple, reproducible, with a very limited increase in operative time, and with only a slight risk of potential harm to the patient. Moreover, it could improve hemostasis and provide greater support for a delicate anastomosis.

Determinants of ejaculatory dysfunction in a community-based longitudinal study.

OBJECTIVE To analyse the incidence of ejaculatory dysfunction (EJD) and its associated bother, and to determine which factors predispose to incident EJD. SUBJECTS AND METHODS Men aged 50-78 years, registered in the general practices in Krimpen a/d Ijssel, the Netherlands, were recruited. Men were excluded if they had a history of prostatectomy, carcinoma of the bladder or prostate and neurogenic bladder disease. A baseline study and three follow-up assessments (I-III), all with questionnaires, i.e. the Benign Prostatic Hyperplasia impact index, International Prostate Symptom Score, International Continence Society (ICS)male sex questionnaire, and additional measurements, e.g. prostate volume, prostate specific antigen, were made at a mean of 2.2-year intervals. We assessed the objective variables of EJD as the ability to ejaculate, ejaculatory volume, painful ejaculation, and their associated bother (information extracted from the ICSmale sex questionnaire). RESULTS At baseline 671 of 1661 (40.4%) men already had EJD; the cumulative incidence of EJD was 16.5%, 24.7% and 33.1% after follow-up I, II and III, respectively. The mean percentage of men who were bothered with reduced ejaculatory volume or painful ejaculation was 18.3% and 40.6%, respectively. Multivariate analysis showed age, Sickness Impact Profile 'social' (questions on social impairment) and erectile dysfunction to be predisposing factors of EJD (P < 0.05 and R(2) = 0.048). When EJD was defined as a significantly reduced ejaculatory volume or anejaculation only, age and previous transurethral resection of the prostate (TURP) were determinants of EJD (P < 0.05 and R(2) = 0.083). Of the men who had TURP after the follow-up, 51.6% already had EJD at baseline. CONCLUSIONS The cumulative incidence of EJD after 6.5 years of follow-up was significant (33.1%) and EJD was bothersome, especially in men with painful ejaculation. Determinants of EJD were age, social impairment and erectile dysfunction. Predisposing factors of significant reduction of ejaculatory volume and anejaculation were age and TURP, although 51.6% of men already had EJD before TURP. Age appears to be the most significant predisposing factor of EJD.