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EUROPEAN UROLOGY 70 (2016) 301–311 available at www.sciencedirect.com journal homepage: www.europeanurology.com Collaborative Review – Prostate Cancer A Critical Analysis of the Current Knowledge of Surgical Anatomy of the Prostate Related to Optimisation of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy: An Update Jochen Walz a,*, Jonathan I. Epstein b, Roman Ganzer c, Markus Graefen d, Giorgio Guazzoni e, Jihad Kaouk f, Mani Menon g, Alexandre Mottrie h, Robert P. Myers i, Vipul Patel j, Ashutosh Tewari k, Arnauld Villers l, Walter Artibani m a Department of Urology, Institut Paoli-Calmettes Cancer Centre, Marseille, France; c b Departments of Pathology, Urology, and Oncology, Johns Hopkins d Medical, Baltimore, MD, USA; University of Leipzig, Leipzig, Germany; Martini Clinic, Prostate Cancer Centre, Hamburg, Germany; e Department of Urology, Humanitas Research Hospital, Rozzano, Italy; f Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; g Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA; h Onze Lieve Vrouw Robotic Surgery Institute, Aalst, Belgium; i Institute of Urology, Lahey Hospital and Medical Center, Burlington, MA, USA; j Global Robotics Institute, Florida Hospital Celebration Health, Celebration, FL, USA; k Prostate Cancer Institute, Department of Urology, Weill Cornell Medical College, New York, NY, USA; l Department of Urology, Centre Hospitalier Régional Universitaire de Lille, Lille, France; m Department Urology, University of Verona, Verona, Italy Article info Abstract Article history: Accepted January 18, 2016 Context: In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy. Objective: To provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP). Evidence acquisition: We searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update. Evidence synthesis: We found new evidence for several topics. Up to 40% of the crosssectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence. Conclusions: This update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains Associate Editor: Stephen Boorjian Keywords: Prostate Prostate cancer Anatomy Neurovascular bundle Sphincter Radical prostatectomy Erectile dysfunction Urinary continence Urethra * Corresponding author. Department of Urology, Institut Paoli-Calmettes Cancer Centre, 232, Bd Ste. Marguerite, 13009 Marseille, France. Tel. +33 491223532; Fax: +33 491223613. E-mail address: walzj@ipc.unicancer.fr (J. Walz). http://dx.doi.org/10.1016/j.eururo.2016.01.026 0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved. 302 EUROPEAN UROLOGY 70 (2016) 301–311 complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes. Patient summary: Based on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time. # 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved. 1. Introduction In 2010, we published a review on the current knowledge of the anatomy of the prostate and surrounding tissue with the aim of helping urologists better understanding the diverse structures encountered during radical prostatectomy (RP) and applying the current nomenclature for these structures correctly [1]. We now present an update, taking the most recent research results into consideration as well as the most recently published technical variations of RP and adding topics that we left out of the previous article. 2. Evidence acquisition We searched the PubMed database to identify original and review articles in English that addressed the anatomy of the prostate and relevant structures adjacent to the prostate, with an emphasis on work published after the publication of our previous review (February 2010 to July 2015). The keywords used were prostate, radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters were reviewed, analysed, [(Fig._1)TD$IG]and summarised, with the consensus of all authors. 3. Evidence synthesis Regarding the pubovesical/puboprostatic ligaments, the accessory pudendal arteries, the vesicoprostatic muscle, and the periprostatic fascia, no new anatomic knowledge was acquired (Figs. 1–4). Consequently, we refer to the previous article for this information [1]. 3.1. Dorsal vascular complex The dorsal vascular complex (DVC) overlies the urethral sphincter ventrally. During its ligation, injury to the sphincter tissue is possible, resulting in potentially decreased postoperative continence. A recent study by Ganzer et al demonstrated that 37% and 30% of the cross-sectional urethral sphincter surface area are laterally overlapped by the DVC at the prostate apex and 5 mm distal to the apex, respectively. The DVC covers the urethral sphincter tissue laterally and dorsally (Fig. 3) [2]. In the case of transverse en bloc ligation of the DVC dorsal to its lateral limits, a substantial portion of the sphincter tissue might be included in the ligation and rendered nonfunctional. To avoid this problem, selective dissection and ligation of the DVC is strongly recommended [2,3]. Fig. 1 – Axial section of prostatic and periprostatic fascia at midprostate. A = apex; AFMS = anterior fibromuscular stroma; B = bladder; DA = detrusor apron; DF = Denonvilliers fascia; DVC = dorsal vascular complex; FTAP = fascial tendinous arch of pelvis; LAF = levator ani fascia; M = midprostate; NVB = neurovascular bundle; PC = pseudocapsule; PPF = periprostatic fascia; PPF/SVF = posterior prostatic fascia/seminal vesical fascia; PRS = perirectal space; PZ = peripheral zone; R = rectum; SV = seminal vesicle; TZ = transition zone; U = urethra; VEF = visceral endopelvic fascia. EUROPEAN UROLOGY 70 (2016) 301–311 [(Fig._2)TD$IG] 303 Fig. 2 – Midline sagittal section of prostate, bladder, urethra, and striated sphincter. B = bladder; CS = colliculus seminalis (verumontanum); DA = detrusor apron; DF = Denonvilliers fascia; DVC = dorsal vascular complex; MDR = medial dorsal raphe; PC = pseudocapsule of prostate; PPF/SVF = posterior prostate fascia/seminal vesicle fascia; PS = pubic symphysis; R = rectum; RU = rectourethralis muscle; SMS = smooth muscle sphincter; SS = striated sphincter; SV = seminal vesicles; U = urethra; VEF = visceral endopelvic fascia; VS = vesical sphincter; VVPM = vesicoprostatic muscle. 3.2. Prostate arterial supply The internal pudendal artery is the prolongation of the internal iliac artery after branching off the obturator artery, [(Fig._3)TD$IG]the vesical arteries, and the superior and inferior gluteal Fig. 3 – Axial section of the sphincteric urethra. A ]FDI$_T[5 = apex; B = bladder; C SMS = circular smooth muscle sphincter; DVC = dorsal vascular complex; EPF = endoplevic fascia; LA = levator ani muscle; LAF = levator ani fascia; L SMS = longitudinal smooth muscle sphincter; M = midprostate; MDR = median dorsal raphe; NVB = neurovascular bundle; PB = pubic bone; PV/PPL = pubovesical/ puboprostatic ligament; R = rectum; SS = striated sphincter; SV = seminal vesicle; U = urethra. arteries. The most frequent origin of prostate arteries is from the internal pudendal artery (35–56%) [4,5]. The common gluteal–pudendal trunk is the next most frequent origin (15– 28%), and less frequently the prostate arteries branch off the obturator artery (10–12%) or the inferior gluteal artery. Per side, there is only one common trunk in most cases (60–76%), and there are anastomoses with the termination of the internal pudendal arteries (24%), contralateral prostate arteries (12%), and superior vesical arteries (8%) [4,5]. After branching off, the artery has a tortuous course obliquely downward in trajectory towards the posterior and inferior part of the bladder and provides several inferior vesical arteries. It terminates with numerous prostate branches, often after a bifurcation, resulting in two main pedicles. The urologist can differentiate a posterior pedicle surrounding seminal vesicles and deferential ducts reaching the prostate base as well as an anterior pedicle surrounding the lateral border of the prostate finally running to the prostate apex as an anterior capsular prostate branch. These latter arteries, when preserved during RP, may relate to postoperative erectile function and penile integrity because they may be responsible for ancillary penile blood flow [6,7]. After reaching the prostate pseudocapsule, the prostate arteries give rise to numerous perforating branches to the prostate, with most penetrations found at the 2 o’clock or 10 o’clock position for the anterolateral pedicle and at the 5 o’clock or 7 o’clock position for the posterolateral pedicle [4]. The anterolateral pedicle vascularises mainly the central gland and the transition zone, whereas the posterior pedicle vascularises most of the peripheral zone and apical area. Note that there is considerable inter- and intraindividual variability in the vascular anatomy. 304 EUROPEAN UROLOGY 70 (2016) 301–311 [(Fig._4)TD$IG] 3.4. Posterior prostatic fascia and seminal vesicles fascia (Denonvilliers fascia) Fig. 4 – Coronal section of the prostate, sphincteric urethra, periprostatic fascia, and associated musculature. CS = colliculus seminalis (verumontanum); CZ = central zone; ED = ejaculatory duct; LA = levator ani muscle; LAF = levator ani fascia; NVB = neurovascular bundle; OI = obturator internus muscle; PC = pseudocapsule of prostate; PF = prostate fascia; PPF = periprostatic fascia; PZ = peripheral zone; SMS = smooth muscle sphincter; SS = striated sphincter; SV = seminal vesicle; U = urethra; VD = vas deferens. 3.3. Exterior stromal edge of the prostate versus ‘‘prostate pseudocapsule’’ There is an ongoing controversy regarding the outer limits of the prostate. The structure often termed the capsule is the exterior stromal edge of the prostate parenchyma, formed by transversely arranged fibromuscular layers of condensed smooth muscle, with a variable number of glands recognised at the outermost prostate surface [8]. Note that this condensed fibromuscular layer may intermingle with the periprostatic tissue, rendering its appearance quite variable [1]. From a microscopic and pathologic point of view, the correct term for this layer would be condensed smooth muscle or the outer edge of the prostate. Despite this microscopic evidence, from a macroscopic and surgical point of view, the defined and distinct outer edge of the prostate, analogous to a capsule, is visibly and grossly apparent during RP in many cases and is used as a landmark for proper dissection [9]. Consequently, the coauthors agreed that the term pseudocapsule might represent an acceptable compromise to respect its pathologic nature versus the clinical appearance of the prostate outer limits in daily practice. Note that the International Anatomical Terminology refers to capsule (pseudocapsule) [10]. A recent work from Muraoka et al investigated the intraand interindividual variations of the posterior prostatic fascia (PPF) and seminal vesical fascia (SVF) (Figs. 1 and 2). They showed that although its configuration appeared to be a firm membranous structure, it was actually recognised as a fascicle of multiple leaves with interlacing branches, with multiple leaves mainly ventrally, and a disorderly, loose connective tissue mainly dorsally [11]. They observed a fusion between the PPF/SVF and the pseudocapsule near the base of the prostate at the insertion of the seminal vesicles (Fig. 2). The PPF/SVF extended and dispersed laterally into the neurovascular bundle (NVB), and periprostatic nerves ran between multiple leaves and appeared embedded in the fascial complex between PPF/SVF leaves and the pseudocapsule.[11] Another recent work by Kim et al suggests that the tissue quality of PPF/SVF varies among patients as its origin might be induced by tissue tension, created by organ development in the pelvis and not by tissue fusion as suggested previously. As this development can vary substantially from patient to patient, the fascia can have a multilayer configuration, a fragmentation into short pieces, or be composed of a thick leaf [12]. This theory supports the observations from Muraoka et al as well as clinical experience, in which tissue quality varies [13]. 3.5. Neurovascular bundle 3.5.1. Neurovascular bundle and pelvic lymph node dissection In the male, the inferior hypogastric plexus, or pelvic plexus, is responsible for the mechanisms of erection, ejaculation, and urinary continence [14]. The pelvic plexus lies within a fibrofatty, flat, rectangular, sagittally oriented plate between the bladder and the rectum [14–17]. Pelvic lymph node dissection (PLND) might be extended into this area. Currently, a standard PLND is defined as a dissection of the fibrofatty tissue between the landmarks of the external iliac artery and the pelvic musculature laterally, the inner femoral canal distally, the common iliac artery or the bifurcation with the ureter proximally, and the bladder wall medially, including a dissection around the internal iliac artery [18,19]. In a recent lymph node mapping study, such a dissection field allows the urologist to correctly stage patients as N0 or N1 in 94% of all cases and removes 87% of all positive nodes [20]. In the same study, a more limited dissection field (external iliac vessels and obturator fossa) correctly staged only 76% of all patients and removed only 52% of all positive nodes [20]. An extended PLND (ePLND) might extend the dissection up to the common iliac arteries as well as to the presacral areas [18,19]. Such a dissection would correctly stage 97% of all patients, and 99% of all positive nodes would be removed [20]. The pelvic plexus and the erectile nerves are at risk in standard dissection during the medial dissection in the area of the internal iliac artery and towards the bladder wall. During ePLND, the nerves are also at risk at their origin in the presacral area and medial to the common iliac vessels. In fact, decreased EUROPEAN UROLOGY 70 (2016) 301–311 erectile function in patients with a more extended yield of lymph nodes relative to patients with a lower yield or no lymph node dissection has been demonstrated [21,22]. Others could not find any influence from the extent of PLND on erectile function [23]. Nevertheless, from an anatomic point of view, ePLND occurs near or inside the pelvic plexus and thus can lead to injury of proerectile nerves. This should be considered when performing PLND during pelvic surgery. 3.5.2. is questionable [29]. Nevertheless, several studies proved that the high anterior release concept with preservation of the anterior nerve fibres improves both erectile function and urinary continence relative to patients who did not undergo a high anterior release [36–38]. It remains unclear whether this effect is a result of the nerve fibres that are preserved at the anterolateral aspect of the prostate or whether it is a result of other aspects, such as less traumatic handling of the NVB; better identification of dissection planes; or other, hidden technical details [39]. Anterolateral nerves of the neurovascular bundle Fibres of the pelvic plexus destined for erectile and urinary function surround the lateral aspect of the bladder neck, the proximal prostate, and the seminal vesicles [15,16,24]. During their course lateral to the prostate, several studies confirmed a spraylike distribution of the nerves on the lateral and anterolateral surface of the prostate up to the 2 o’clock and 10 o’clock positions [24–30]. Ganzer et al, using computerised planimetry, identified the largest percentage of periprostatic nerve surface in the posterolateral position. The periprostatic nerve distribution was variable, with up to 19% of the overall nerve surface in the anterolateral position [30]. This finding was corroborated by Alsaid et al, who found that at the midpart the NVBs became more dispersed, with less than two-thirds of the periprostatic nerve fibres remaining in the posterolateral regions and one-third in the anterior and anterolateral regions. At the apex, 60% of the nerves were located posterolaterally, and 40% were located anterolaterally [31]. Clarebrough et al reproduced the methodology of Ganzer et al and showed that the overall proportion of nerve surface on whole-mount sections increased at the anterolateral side of the prostate, from 6.0% at the base to 7.6% at the midpart to 11.2% at the apex, suggesting that especially at the apex nerve fibres are more predominant along the anterolateral aspect of the prostate [32]. All these differing results can be explained by the interindividual variability of the anatomy as well as by the difference in methodology (nerve surface vs number of nerve fibres). 3.5.3. 305 Function of nerves lateral to the prostate The role and function of the anterolateral nerves on the prostate are controversial, despite several studies that included immunohistochemical staining of these nerve fibres. Alsaid et al showed in a foetus aged 17 wk using three-dimensional (3-D) reconstruction that sympathetic, parasympathetic, and sensory nerve fibres are found on the anterolateral aspect of the prostate. Unfortunately, they did not provide nerve counts [33]. Ganzer et al showed that up to 14.6% of all parasympathetic nerve fibres are found anterolaterally, but in their study at the apex, only 1.5% of all parasympathetic nerves were found anteriorly [34]. A similar study by Costello et al demonstrated that only 7% of all parasympathetic nerve fibres are found on the anterolateral aspect of the prostate [35]. As erectile function is assured by parasympathetic fibres, the physiologic nature of these fibres makes participation in erectile function possible, but because of the low percentage of anterolateral parasympathetic fibres, their influence on overall function 3.5.4. Compartmentalisation of the neurovascular bundle Costello et al divided the NVB into the anterior fibres mainly innervating the levator ani and the prostate and the more posteromedial located fibres mainly innervating the corpora cavernosa [16]. Tewari et al proposed a longitudinal trizonal compartmentalisation of the NVB by dividing it into the proximal neurovascular plate, which is synonymous with the already-discussed pelvic plexus; the predominant NVB; and the accessory neural pathways [40]. Accessory neural pathways were noted within the layers of the periprostatic fascia up to the anterolateral aspect of the prostate. Two sets of neural tissue were identified: one superficial that lays inside of the periprostatic fascia and a deeper group of nerves travelling within the pseudocapsule and probably responsible for direct innervation of the prostate [40]. In fact, a recent study by Ganzer et al demonstrated that the total nerve surface decreases by 75% from the level of the seminal vesicles to the urethra, from 50.2 mm2 to 13.3 mm2, suggesting a role for these nerves other than innervation of the corpora cavernosa [41]. Another study by Alsaid et al based on 3D reconstruction demonstrated that at the prostate apex and the urethra, the NVB is separated into two distinct groups: the cavernous nerves and corpus spongiosum nerves [31]. They demonstrated that the cavernous nerve fibres running to the corpora cavernosa were a continuation mainly of the fibres running on the anterior and lateral aspect of the prostate. The corpus spongiosum nerve fibres running to the corpus spongiosum were found to be a continuation of the fibres running at the posterolateral aspect of the prostate [42]. They concluded that the ideal dissection plane during nerve sparing should include the preservation of the anterolateral tissue and fascia to avoid cavernous nerve lesions [31]. It is noteworthy that despite extensive research in the field of prostate anatomy, the exact anatomy of the fascia and the detailed function of the nerve fibres surrounding the prostate remain controversial and at times contradictory. 3.6. Anatomic landmarks for nerve sparing and grading of nerve sparing extent In daily practice, the substantial interindividual and intraindividual variations do not allow the urologist to reproduce the same surgical dissection in every patient, but the multilayered character of the periprostatic fascia allows choice in the dissection between nerves and prostate 306 EUROPEAN UROLOGY 70 (2016) 301–311 pseudocapsule with the aim of leaving a more or less thick tissue layer on the prostate as a safety margin. In cases with a low risk of extraprostatic extension (EPE), a closer dissection and in cases with a higher risk of EPE a wider dissection plane can be chosen. This approach was termed incremental nerve sparing [43,44]. It is known that EPE is in most cases only a matter of millimetres, which could allow a nerve-sparing procedure in selected cases with focal EPE [45]. Inoue et al evaluated the distance between cancer and the NVB at the classical 5 o’clock and 7 o’clock position in prostates without nerve sparing. In patients without EPE, they found a mean distance of 3.3 mm (standard deviation [SD]: 2.6), 3.4 mm (SD: 2.7), and 3.7 mm (SD: 2.4) at the apex, midgland, and base, respectively. In patients with EPE, the distance between cancer and the NVB was 2.0 mm (SD: 1.9), 1.9 mm (SD: 1.9), and 1.8 mm (SD: 2.1) at the apex, midgland, and base, respectively [46]. Note that in an individual case, the nerves could be in direct contact with the NVB. This observation corroborates the possibility of nerve-sparing procedures despite the presence of EPE in well-selected patients. Depending on the dissection plane chosen during the procedure, several technical variations are possible. Previously, we described intrafascial, interfascial, and extrafascial dissection (Fig. 5a and 5b; Table 1) [1]. Intrafascial dissection is considered a dissection that follows a plane on the pseudocapsule, remaining internal to the prostatic fascia at the antero- and posterolateral aspect of the prostate and anterior to the PPF/SVF. The intrafascial approach allows a whole-thickness preservation of the NVB. Interfascial dissection of the NVB is considered a dissection within the thickness or between the leaves of the periprostatic fascia and includes incremental nerve sparing. Depending on anatomic variations, the NVB might be prone to partial resection. This approach allows a greater safety margin around the prostate relative to the intrafascial dissection, presumably resulting in an oncologically safer approach [47,48]. The extrafascial dissection is a dissection [(Fig._5)TD$IG] Fig. 5 – (a) Overview of an axial section of the prostatic and periprostatic fascia at midprostate (prostate rotated counterclockwise). (b) Enlarged axial section with three dissection planes: intrafascial, interfascial, and extrafascial. (c) Enlarged axial section with three dissection planes according to the Pasadena consensus [44]: full, partial, and minimal nerve sparing. (d) Enlarged axial section with four dissection planes according to Tewari et al [40]: 1 = dissection below veins, 2 = dissection on the veins, 3 = dissection distant from the veins, and 4 = extrafascial dissection. (e) Enlarged axial section with five dissection planes according to Schatloff et al [50]: 1 = extrafascial dissection, 2 = sharp dissection distant from arteries, 3 = sharp dissection on arteries, 4 = sharp dissection at the level of arteries, and 5 = blunt dissection below arteries. LA = levator ani muscle; LAF = levator ani fascia; PC = pseudocapsule of prostate; PPF = periprostatic fascia; R = rectum. 307 EUROPEAN UROLOGY 70 (2016) 301–311 Table 1 – Overview of the different dissection planes for nerve sparing during radical prostatectomy and their influence on safety margin and nerve-sparing quality Author Dissection plane Safety margin to avoid PSM Low High [TD$INLE] Nerve-sparing quality Good Previous article Walz et al [1] Pasadena consensus, Montorsi et al [44] Tewari et al [40] Schatloff et al [50] Intrafascial Full nerve sparing Grade 1 Grade 5 Poor [TD$INLE] Interfascial Partial nerve sparing Grade 2 Grade 4 Grade 3 Minimal nerve sparing Grade 3 Grade 2 Extrafascial NA Grade 4 Grade 1 NA = not applicable; PSM = positive surgical margin. carried out lateral to the levator ani fascia and posterior to the PPF/SVF. In this case, the NVB will be completely resected. This approach results in the largest amount of tissue surrounding the prostate and thus is the most oncologically safe dissection, but it carries with it probable complete erectile dysfunction if done bilaterally [47]. Alternate terminology for dissection planes has been suggested by a consensus panel using the terms full, partial, and minimal nerve sparing for the intrafascial, interfascial, and ‘‘sub’’ extrafascial dissection, respectively (Fig. 5c; Table 1) [44]. Note that the estimation of nerve-sparing extent is subjective, especially in the category of interfascial or partial nerve sparing. Recent studies pushed this concept even further and suggested subdividing the interfascial dissection into near and far interfascial dissection planes relative to the pseudocapsule, proposing grading systems to define the extent of tissue margin on the prostate [6,43]. Tewari et al proposed a grading system based on four grades of dissection [43]. They used the veins on the lateral aspect of the prostate as vascular landmarks for the definition of the dissection planes as well as a scaling system, with 1 being maximal nerve sparing and 4 being no nerve sparing (Fig. 5d; Table 1). A dissection between the periprostatic veins and the pseudocapsule of the prostate is considered a grade 1 dissection. Cases in which the dissection is performed just on the veins are considered grade 2 dissection. When leaving more tissue on the veins and the prostate, it is considered a grade 3 dissection, and an extrafascial dissection is a grade 4 dissection [43]. Using the Tewari system, Srivastava et al demonstrated that the early return of continence was associated with the grade of nerve sparing, in which 72% of patients with grade 1 nerve sparing had early continence versus 55%, 46%, and 44% for grades 2, 3, and 4, respectively [49]. Data on erectile function were not available. Patel and coworkers proposed an inverse five-grade scale of dissection, in which grade 5 represents optimal nerve sparing and grade 1 no nerve sparing (Fig. 5e; Table 1) [50]. They used the arterial periprostatic vasculature as a landmark, with a ‘‘landmark artery’’ running on the lateral border of the prostate as either a prostate or capsular artery. Those arteries were identified in 73% of all prostate halflobes [6]. Maximum nerve sparing was termed a grade 5 dissection, and the dissection is performed without the need for sharp dissection between this artery and the pseudocapsule outside the prostatic fascia. A grade 4 dissection is performed using sharp dissection in a plane between the artery and the prostatic pseudocapsule across the NVB. Intraoperatively, the dissection is confirmed by the presence of a strip of adipose tissue over the prostate and an absence of arterial vessels. For a grade 3 dissection, the plane of nerve sparing is created at the artery’s lateral aspect; therefore, the artery is clipped at the level of the prostate pedicle. Intraoperatively, the dissection is identified by the presence of a strip of adipose tissue over the prostate, with the artery on top. For a grade 2 dissection, nerve sparing is performed several millimetres lateral to the artery, following the prostatic contour. Intraoperatively, the dissection is identified by the presence of a thick fat strip over the prostate, with arteries embedded. Finally, for a grade 1 dissection, an extrafascial dissection is performed [50]. Using this grading system, Schatloff et al reported on the amount of nerve tissue on the prostate according to the degree of nerve sparing. They could confirm that with increasing degrees of nerve sparing, the amount of nerve tissue on the prostate decreased [50]. Further studies evaluating the impact of different grades of nerve sparing on functional outcomes are awaited. Bearing in mind that the anatomy of the nerves may vary substantially, the concept of different dissection planes aims more for an incremental security margin on the prostate to avoid positive surgical margins (PSMs) than for true incremental nerves sparing. Incremental nerve sparing would imply that the course and location of erectile nerve fibres can reliably be identified, which is not the case because of their microscopic nature and the varying anatomy. The degree of nerve sparing with this approach is uncertain, and the true extent of nerve fibre preservation in an individual patient cannot reliably be controlled or predicted. In contrast, the amount of tissue remaining on the prostate to avoid a PSM can be well controlled during the procedure, with the aim of achieving an incremental safety margin to cover the pseudocapsule and cancer, if 308 EUROPEAN UROLOGY 70 (2016) 301–311 present. For this reason, the term incremental safety margin instead of incremental nerve sparing may better reflect this technical variation [39]. So far, there is no consensus on which grading system should be used, and a standard system would need clear and reproducible landmarks to provide comparability and reproducibility [44]. Moreover, selection of patients for such an incremental safety margin approach depends on patient and cancer characteristics and is the fundamental concern with this technique. Address this issue is beyond the scope of this review but needs to be taken into consideration when these variations in surgical techniques are applied in daily practice. 3.7. this paper as the urethral sphincter (musculus sphincter urethrae) [55]. This terminology seems more appropriate as most of the vesical sphincter tissue is found at the level of the (caudal) urinary bladder, and its function is to close the storage organ bladder at the bladder level and not at the urethral level. Moreover, the vesical sphincter helps separate the storage organ bladder form the genital part of the genitourinary tract that then serves for its genital function (ejaculation). At the same time, the urethral sphincter has its function at the level of the urethra as it closes the urethra at a distance to the bladder when activated [55]. Consequently, the terms vesical sphincter and urethral sphincter will be used in the following text to replace the terms internal and external urethral sphincter, respectively. Pelvic floor musculature 3.8.1. The innermost muscle of the anterior pelvis is the levator ani muscle. Close to the urethral sphincter, it has been termed the puboperinealis muscle and represents the anteromedial component of the levator ani [3,51,52]. Voluntary contraction of the puboperinealis muscle pulls the urethra and prostate forward and upward, resulting in closure of the urethra [51,53]. Innervating this muscle are fibres of the long pelvic nerve, or levator ani nerve, which runs on the levator ani surface just lateral to the fascial tendinous arch (Fig. 6) [54]. For full functional integrity of the puboperinealis and the quick-stop mechanism, this nerve needs to be identified and preserved. It might be injured by incision of the endopelvic fascia and by mobilisation of the levator ani laterally away from the prostate [54]. 3.8. Bladder neck and urinary sphincter There are two well-recognised urinary sphincter systems: (1) a proximal internal urethral sphincter, referred to in this paper as the vesical sphincter (musculus sphincter vesicae), and (2) the distal external urethral sphincter, referred to in [(Fig._6)TD$IG] Fig. 6 – Intraoperative picture of the long pelvic nerve or the levator ani nerve (arrow) on the left side of the prostate. Picture taken at the moment of the endopelvic fascia opening (pelvic wall on the left side, prostate on the right side). Reproduced with permission from V. Patel, Ohio State University (Columbus, OH, USA). Bladder neck and vesical sphincter The bladder neck is the anatomic area of the urinary bladder outlet and the entrance to the prostatic urethra. It is formed by several structures, including detrusor muscle, the vesical sphincter, and adjacent proximal prostatic tissue. The detrusor muscle consists of a densely interwoven network of three recognised smooth muscle layers: an inner longitudinal layer, a middle circular layer, and an outer longitudinal layer [55,56]. The detrusor is anteriorly and laterally in close contact with the bladder neck, but there is no participation of any of the three layers in the formation of the vesical sphincter. Some anterior fibres of the outer longitudinal muscle layer reach out over the prostate to reach the os pubis in puboprostatic/pubovesical ligaments. This sheath of smooth muscle is also termed the anterior detrusor apron (Fig. 2) [1,57]. Posterior fibres of the outer longitudinal muscle layer cover the trigone posteriorly and reach out over the bladder neck to penetrate the posterior aspect of the prostate. This structure is also termed the vesicoprostatic muscle or posterior detrusor apron (Fig. 2) [1,58,59]. These muscle bundles attach the urinary bladder in the pelvis but do not participate in the sphincter system. The trigone is a creaseless, triangular area extending anteriorly from the two ureteral orifices to the urethral opening, with superficial submucosal longitudinal smooth muscle fibres [55]. This smooth muscle extension is the site of formation of middle-lobe benign prostatic hyperplasia (BPH). At its cranial border, the trigone consists of a transverse, submucosal band formed by the prolongation of ureteral muscle, extending from one ureteral orifice to the contralateral orifice [55]. The main part of the trigone is formed by fibres of the vesical sphincter, which is an elliptic structure formed by circular smooth muscle fibres surrounding the urethral opening circumferentially. The urethral opening is eccentrically positioned and located in the anterior third of the ellipsis. Posteriorly, the circular muscle fibres reach almost to the ureteral orifices (Fig. 2) [55]. This muscular structure is part of the vesical sphincter that assures continuous urinary continence as well as bladder neck closure during ejaculation to avoid retrograde ejaculation. Inferiorly, circular fibres of this muscle surround the proximal prostatic urethra down to the colliculus seminalis. This part of the sphincter is modified by and interspersed with the development of BPH, and the 309 EUROPEAN UROLOGY 70 (2016) 301–311 intravesical part may be displaced upward, in this case into the bladder lumen. The so-called bladder neck–sparing technique is performed in this anatomic area to improve postoperative continence. To date, there is a controversy regarding the effect of bladder neck sparing on urinary continence, and no clear conclusion for or against bladder neck sparing can be drawn [44,60–62]. results at the same time. Today, RP is no longer an all-in-one procedure but rather an individualised operation that should take many details into consideration. 3.8.2. Study concept and design: Walz, Artibani. Urethral sphincter The urethral sphincter complex is found primarily distal to the prostate apex. It is in close relationship with but independent from the levator ani muscle (pars puboperinealis) and thus independent of the pelvic floor musculature [47,63,64]. The urethral sphincter itself consists of two muscle types (Fig. 2 and 3). First, the outer striated muscle fibres, described to be omega shaped and extending to the apex and the anterior surface of the prostate [65–68]. Recently, an extension of the striated muscle not only on the outside of the apex but also inside the apex was suggested [69]. Second, an inner muscle layer of the urethral sphincter surrounds the urethra completely and consists of smooth muscle fibres (outer circumferential and an inner, longitudinally oriented layer) and elastic tissue [64]. The smooth muscle layer has its proximal limits at the level of the colliculus seminalis or verumontanum (Fig. 2) [30,65]. The shape of the prostate at the apex may vary substantially, directly influencing the form and length of the urethral sphincter after emerging from the apex because parts of the urethral sphincter can be found inside the prostate apex as a distinct structure surrounded by prostatic tissue [47,69]. The apex may overlap the urethral sphincter circumferentially, symmetrically bilaterally, asymmetrically unilaterally, anteriorly only, or posteriorly only, or it can end bluntly above the sphincter [70]. Significant overlap might render the preservation of the entire urethral sphincter difficult. Based on the above anatomy, Schlomm et al described a full-length preservation of the urethral sphincter by identifying and dissecting the distinct striated and smooth muscle part of the sphincter inside the prostate apex until the colliculus seminalis is encountered [69]. This technique allows preservation of the entire length of the urethral sphincter system irrespective of the apical shape. This approach resulted in early continence results of 50% 1 wk after catheter removal and 97% at 12 mo [69]. To date, it is unclear whether dissection proximal to the colliculus seminalis or just distal to the colliculus results in a significant difference in the results [69,71], but full-length preservation of the urethral sphincter up to the colliculus seminalis clearly preserves a longer urethral sphincter and thus may result in better continence. 4. Conclusions Recent focus on the anatomy of the prostate and its surrounding tissue has produced expanded details applicable to surgical technique. Based on detailed anatomy and its variations, the surgeon should individualise the dissection in a patient according to cancer characteristics by altering the technique to improve both oncologic and functional Author contributions: Jochen Walz had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Acquisition of data: Walz, Ganzer. Analysis and interpretation of data: Walz, Epstein, Ganzer, Graefen, Guazzoni, Kaouk, Menon, Mottrie, Myers, Patel, Tewari, Villers, Artibani. Drafting of the manuscript: Walz. Critical revision of the manuscript for important intellectual content: Walz, Epstein, Ganzer, Graefen, Guazzoni, Kaouk, Menon, Mottrie, Myers, Patel, Tewari, Villers, Artibani. Statistical analysis: Walz. Obtaining funding: None. Administrative, technical, or material support: Walz, Villers, Tewari, Myers, Patel. Supervision: Artibani. Other (specify): None. Financial disclosures: Jochen Walz certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. References [1] Walz J, Burnett AL, Costello AJ, et al. A critical analysis of the current knowledge of surgical anatomy related to optimization of cancer control and preservation of continence and erection in candidates for radical prostatectomy. Eur Urol 2010;57:179–92. [2] Ganzer R, Stolzenburg JU, Neuhaus J, Weber F, Burger M, Brundl J. 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