UNIVERSITA’ DEGLI STUDI DI PISA
SCUOLA DI SPECIALIZZAZIONE IN UROLOGIA
Direttore: Prof. Cesare Selli
THE COLLAR TECHNIQUE FOR APICAL DISSECTION
IN ROBOT-ASSISTED RADICAL PROSTATECTOMY
Relatore:
Prof. CESARE SELLI
Correlatore:
Dott. ALEXANDRE MOTTRIE
Tesi di Specializzazione di:
FILIPPO MARIA TURRI
Matr. n°489424
ANNO ACCADEMICO 2015-2016
I have perceiv’d that to be with those I love is enough, To stop in company with the rest at evening is enough,
To be surrounded by beautiful, curious, breathing, laughing flesh is enough…
There is something in staying close to men and women and looking on them, and in the contact and odor of them, that pleases the soul well,
All things please the soul, but these please the soul well.
INDEX
1. INTRODUCTION ... 7
2. MALE SPHINTERIC SYSTEM ... 8
2.1 DEVELOPMENT OF THE PREPROSTATIC AND URETHRAL SMOOTH MUSCLE SPHINCTERS ... 8
2.2 ANATOMY OF THE URINARY SPHINCTERS ... 11
2.2.1 Smooth muscle sphincters ... 12
2.2.2 Striated muscle sphincters ... 16
2.2.3 Innervation of the urinary sphincters ... 20
2.3 URINARY CONTINENCE ... 21
3. SURGICAL ANATOMIC AND FUNCTIONAL CONSIDERATIONS ... 22
3.1 THE ANATOMICAL CONCEPT ... 22
3.2 THE PHYSIOLOGICAL CORRELATE ... 25
3.3 CONTRIBUTING FACTORS IN POST-PROSTATECTOMY INCONTINENCE ... 28
4. ROBOT-ASSISTED RADICAL PROSTATECTOMY ... 33
4.1 THE RISE OF ROBOTIC SURGERY ... 33
4.2 OUTCOMES OF ROBOT-ASSISTED RADICAL PROSTATECTOMY 36 4.2.1 Perioperative outcomes ... 36
4.2.2 Oncological outcomes ... 37
4.2.3 Incontinence following RARP ... 42
4.2.4 Potency following RARP ... 44
4.2.5 Impact of the learning curve on the results of RARP ... 46
5. MATERIALS AND METHODS ... 49
5.1 RATIONALE ... 49
5. 2 THE COLLAR TECHNIQUE: STEP BY STEP DESCRIPTION ... 51
5.3 STUDY POPULATION ... 54 5.4 OUTCOMES ... 55 5.5 PATHOLOGICAL EXAMINATION ... 55 5.6 STATISTICAL ANALYSES ... 55 6. RESULTS ... 56 7. CONCLUSIONS ... 65 8. ACKNOWLEDGEMENTS ... 67 9. REFERENCES ... 69
7
1. INTRODUCTION
Apical dissection is the most important step in radical prostatectomy, because it affects not only cancer control, but also postoperative continence and sexual function. Positive surgical margins (PSM) occur frequently in apical lesions and they have a negative impact in prostate cancer control. In contrast, preservation of urethral sphincter length is one of the most important factors for postoperative continence recovery. Apical dissection is therefore a difficult step in radical prostatectomy since a balance must be found between two conflicting needs [1]. The aim of the present study is to describe the Onze Lieve Vrouw (OLV) Hospital technique for apical dissection during Robot-Assisted Radical Prostatectomy (RARP) and to provide an analysis of the oncological and functional results. This technique was developed in 2016 by Dr. Alexandre Mottrie, one of the pioneers of robotic surgery, with whom I have the privilege to work since January 2017.
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2. MALE SPHINTERIC SYSTEM
2.1 DEVELOPMENT OF THE PREPROSTATIC AND URETHRAL
SMOOTH MUSCLE SPHINCTERS [2]
The smooth muscle of the bladder outlet and that of the preprostatic urethra are formed independently but become continuous during subsequent development. Muscle fibers differentiate in layers from mesenchymal cells with the same orientation. Thus, very early in fetal life, three smooth muscle systems can be detected: (1) the musculature of the bladder base, (2) the smooth urethral musculature, and (3) the prostatic smooth musculature, which develops independently of the other two.
Fig. 1
The bladder base segment is composed of the deep and superficial trigonal systems. The circular fibers forming the deep trigone develop first at 3 weeks to form the trigonal ring. A week later, the longitudinal fibers of the superficial trigone related to the ejaculatory ducts and the ureteral musculature appear and extend from the verumontanum to the ureteral orifices.
The urethral smooth muscle that will form the preprostatic sphincter appears around 5 weeks of gestation as two layers: (1) an inner longitudinal and (2) an outer more or less obliquely oriented circular layer. These layers arise separately from those of the bladder and are not connected to the detrusor at this stage. Only later and secondarily do they become continuous with the corresponding longitudinal and circular muscles of the bladder neck.
9 sphincter. The preprostatic sphincter, as noted, is closely related to the formation of the adjacent transition zone.
The prostatic musculature develops in the outer stromal layer of the primitive prostate synchronously with that of the bladder neck. The slender fibers are distinguishable from the coarser smooth muscle of the trigone and the urethra as they surround the urethra except for the dorsomedial wall.
Early development of the striated sphincter
At 5 weeks, before the primitive prostatic ducts are formed, the primordium of the external striated urethral sphincter is in place over the transverse bundles of smooth muscle of the ventral wall of the prostatic urethra. Now clearly striated, the primordium develops dorsally and makes contact with the rectal musculature at the site where the rectourethralis will develop.
Fig. 2
By 9 weeks, the striated sphincter, which will differentiate into the prostatic striated sphincter and the membranous urethral sphincter, covers the ventral side of the urethra all the way to the bladder neck. On the dorsal side, the muscle coat is incomplete because the entry of the müllerian and wolffian ducts limits its proximal distribution. Here, the muscle has the shape of a horseshoe, becoming doughnut-shaped distally as it encircles what will become the membranous urethra. Cranially, the bundles insert into the prostate and their free ends attach to the dorsal raphe.
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Glandular development
The mucosal buds expand from the dorsum of the urethra on both sides and develop into lobes as they intrude against the striated musculature. The two lateral portions of the developing prostate fuse in the midline anteriorly, forming the anterior commissure, which is complete proximally but may be incomplete distally. The growth of the prostate thins the muscle surrounding the prostatic urethra ventrally and laterally.
The striated sphincter not only covers the smooth urethral musculature and immature prostate but also inserts into the prostatic substance in the capsule and is in contact with the circular muscle of the fundus ring.
Development of the striated sphincter after birth
At term, the prostatomembranous sphincter extends along the urethra from the bladder neck to the perineal membrane. The proximal portion of the sphincter, called the prostatic striated sphincter, is most developed over the central part of the prostate, where it extends three-quarters of the way around. At the caudal end, where the distal portion of the sphincter meets the pelvic floor, the membranous striated sphincter lies above the perineal membrane between it and the so-called superior layer of the urogenital diaphragm. Here, the muscle is distributed more uniformly around the urethra but is still relatively deficient dorsally. As the prostate develops bilaterally around the urethra to meet in a ventral commissure, the fibers of both prostatic sphincters are displaced and thinned. These changes account for the difficulties that have been encountered in describing them accurately. Moreover, the prostatic lobes may not join distally at the commissure, thus allowing direct contact between sphincter and urethra.
By 4 years of age, the striated sphincter has extended from the trigonal ring to a point slightly beyond the transverse perineal muscle. Evidence that a true urogenital diaphragm does not form is that the sphincters do not lie above it.
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2.2 ANATOMY OF THE URINARY SPHINCTERS [2]
Although many anatomists have studied and described the male sphincteric mechanisms, it is still difficult to form a unified construction from the various interpretations. The sphincteric muscles are closely interrelated both structurally and functionally, accounting for the problem of separating them by an anatomic approach. The internal sphincter that holds urine above the prostate is considered as part of the vesical neck sphincteric system. Most studies identify some or all of at least five components of the prostatic sphincter mechanism, although by many different names.
SMOOTH MUSCLE
SPHINCTERS STRIATED MUSCLE SPHINCTERS
Preprostatic sphincter involuntary sphincter, vesical neck sphincter, prostatic smooth muscle sphincter, internal sphincter
Prostatomembranous striated sphincter Passive prostatic sphincter passive sphincter,
passive smooth sphincter
Prostatic striated sphincter external striated sphincter, striped compressor of the prostatic urethra (Haines), compressor prostatae (Albinus), sphincter urethrae prostaticae (Kohlrausch), sphincter externe de la vessie (Cadiat)
Membranous urethral sphincter external sphincter, external voluntary sphincter, distal intrinsic urethral sphincter (Gosling), intrinsic external sphincter, intramural external sphincter
Periurethral striated sphincter
(pubococcygeus) external intrinsic striated urethral sphincter, distal intrinsic striated urethral sphincter, extrinsic periurethral musculature, periurethral striated muscle, periurethral levator ani muscle
The greatest anatomic support is found for two smooth muscle sphincters—the preprostatic sphincter and the passive prostatic sphincter—and three striated muscle sphincters—the prostatic striated sphincter, the membranous urethral sphincter (together termed the prostatomembranous urethral sphincter), and the periurethral striated sphincter. The prostate itself maintains the shape of the bladder neck and allows the preprostatic sphincter to assume its role in preserving continence.
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2.2.1 SMOOTH MUSCLE SPHINCTERS a) Preprostatic sphincter and vesical neck
The vesical neck sphincteric system consists of bundles of the middle circular layer of the detrusor that run obliquely forward and down around the urethral orifice to join the deep layer of the anterior longitudinal bundles of the outer coat. This layer appears as concentric, asymmetric rings and forms what has been called the fundus ring or trigonal ring. In addition, the lateral portions of the posterior longitudinal bundle pass around either side to join anteriorly at a lower site, forming an arch that is concave posteriorly, the so-called detrusor arch.
Fig. 3
Even though the vesical neck structurally is not a true sphincter, it can be observed by cineradiography to hold urine at the bladder outlet and so is commonly called the internal sphincter. Its combined smooth muscle and elastic fibers compress the soft mucosal lining to achieve continence.
The preprostatic sphincter is in continuity with the middle circular layer of the bladder that forms the fundus ring but is embryologically, morphologically, and functionally quite different. It consists of a cylinder of smooth muscle with circularly oriented fibers that lies beneath the urethral mucosa inside the transition zone of the prostate. It encircles the urethra for a distance of 1 to 1.5 cm and ends at the upper margin of the verumontanum, where the preprostatic urethra
13 terminates. The proximal portion surrounds the bladder neck and extends into the base of the prostate, where it becomes continuous with the smooth muscle of that organ: a single sphincteric aggregation of smooth muscle is found that consists of a part of the vesical neck musculature and the preprostatic sphincter in continuity distally with the passive prostatic musculature. Thus the male proximal urethra may be viewed as a continuation of the bladder wall, although the elements are developmentally distinct.
Fig. 4
The fibers of the vescical neck and preprostatic sphincter are distinctly different morphologically and functionally from those of the adjacent detrusor. Not only are they smaller in size and mixed with elastic fibers and collagen, but they have a separate innervation composed of sympathetic noradrenergic terminals.
Considered a part of the preprostatic sphincter, the portion of the superficial
trigone in the urethra is a longitudinal band of fine bundles of small diameter
smooth muscle cells. Running on the posterior wall within the circular coat of the preprostatic sphincter, the band extends from its origin in the superficial trigone to the region of the verumontanum, where it becomes continuous with the musculature of the ejaculatory ducts.
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Nerve supply
The preprostatic sphincter is innervated by noradrenergic nerves from the sympathetic system similar to those supplying the smooth muscle of the prostate. Sympathetic nerve stimulation not only empties the prostatic acini but, by closing the preprostatic sphincter, also prevents retrograde flow of ejaculate at the time of contraction of the prostatic musculature. In the presence of sympathetic hyperactivity, the sphincter may not open reflexly on detrusor contraction, resulting in obstruction to voiding.
Sensory input from the vesical outlet enters through the sympathetic and parasympathetic nerves in the inferior hypogastric (pelvic) plexus through the inferior mesenteric ganglia and also through the pelvic nerves via dorsal nerve roots into the dorsal columns of the lumbar and sacral cord.
b) Passive prostatic sphincter
In the male, in addition to the activity of the preprostatic sphincter, continence is aided by a more distal passive sphincter that lies in the prostatomembranous urethra. It is composed of compact fibers of smooth muscle combined with fibroelastic tissue and is distributed semicircularly along the inframontane urethra. These muscle fibers are similar to those found more proximally in the preprostatic sphincter but are intimately related to the striated muscle bundles of the adjacent prostatomembranous sphincter. In addition, an inner longitudinal layer of smooth muscle distal to the verumontanum is continuous with the bundles of the preprostatic sphincter.
The deeper layer of semicircular fibers of the passive sphincter becomes more dense distally near the membranous urethra. Here, the muscle fibers form a ring around the urethra between the inner longitudinal smooth muscle layer and the prostatic striated sphincter external to it. The circular smooth muscle fibers are found mixed with circularly oriented striated fibers. The smooth muscle fibers thin out within the membranous urethra but are still present at the entrance to the bulbar urethra. The smooth muscle in the passive prostatic sphincter does not appear to have a specific sphincteric organization but acts throughout the entire distal prostatic urethral segment as a supplement to the closure capabilities of the passive
15 continence mechanism that is provided by the slow-twitch fibers of the prostatic striated sphincter with which it intermingles. During voiding cystography after prostatic adenomectomy, although on the command to “hold,” the urinary stream can be seen to be at first cut off sharply by voluntary activity at the level of the membranous urethral sphincter, the site of urethral closure is seen to gradually move proximally because of the tone of the passive sphincter.
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2.2.2 STRIATED MUSCLE SPHINCTERS
The voluntary external sphincter mechanism consists of two separate muscular components. One is an intramural prostatomembranous sphincter that itself may be considered to have two parts: a prostatic striated sphincter and a membranous urethral sphincter. The other sphincter is extramural: the periurethral striated sphincter.
a) Prostatomembranous striated sphincter
The prostatomembranous striated sphincter may be divided into a prostatic striated sphincter and a membranous urethral sphincter. Actually, these two sphincters are anatomically and functionally so similar that they may be best considered as the prostatic and membranous portions of a prostatomembranous sphincter. However, each influences a different part of the prostatic urethra, making a distinction necessary.
Fig. 5 Prostatic striated sphincter
The proximal, prostatic part of the prostatomembranous sphincter consists of striated muscle fibers that cover the anterior and lateral surfaces of the prostate, forming the prostatic striated sphincter. The muscle layer is especially thick over the anterior surface of the prostate, becoming thinner as the fibers sweep around laterally and dorsally. The muscle bundles fuse with the anterior fibromuscular stroma, and only with difficulty can they be dissected from the prostate. Near the
17 bladder neck, the muscle fibers often lie posterolateral to the prostate in continuity with the vesical neck fibers and the deep trigone. Distal to the neck, they run obliquely forward over the lateral surfaces of the prostate. About halfway between the bladder neck and the prostatic apex, they become transversely oriented and envelop the anterior surface of the prostate, whereas more distally, the striated muscle sheet almost completely surrounds the apex of the prostate except for a posterior gap.
Distally, the anterior extension of the prostatic striated sphincter merges with the membranous urethral sphincter. The longitudinally oriented puboprostatic muscle, an extramural muscle from the levator system, lies on either side of the prostatic striated sphincter. Although a separate structure, it reinforces the activity of the prostatic sphincters.
If prostatic development about the anterior commissure is deficient, the prostatic portion of the prostatic striated sphincter may lie in direct contact with the urethra at a point distal to the prostatic apex. The intervening smooth muscle layer of the passive sphincter would also be lacking, leaving the striated sphincters exposed to injury during total retropubic prostatectomy.
Membranous urethral sphincter
The membranous portion of the striated sphincter lies distal to the prostatic portion. It may be as long as 2 cm and as thick as 0.6 cm. The fibers are more circularly oriented than those of the prostatic striated sphincter so that they completely surround the urethra from the anterior decussation of the fibers of the prostatic portion of the sphincter to the level of the perineal membrane and the bulbous urethra. The perineal body provides a point of insertion.
Muscle types
The muscles of the prostatomembranous striated sphincter differ from the skeletal muscle of the periurethral striated sphincter, a part of the pubococcygeus. Many of its fibers are one-third as large as those of the pubococcygeus and are fatigue-resistant, slow-twitch fibers that typically have a high content of lipid and mitochondria (Type I fibers). These fibers have a different response to repeated stimulation. They are not only slower to fatigue and thus can maintain tone in the posterior urethra for long periods to maintain continence, but they are also adapted
18
for sustained contraction.
Nerve supply
The prostatic and membranous striated sphincters are innervated solely by motor somatic fibers; there is no autonomic contribution to the striated musculature in humans. The somatic supply comes from the ventral root of S3, with some contribution from S2. It continues in branches of the pelvic (splanchnic) nerve and passes to the pelvic (inferior hypogastric) plexus. This innervation of the intrinsic striated urethral sphincters is in contrast to the supply to the periurethral striated sphincter (pubococcygeus) that is transmitted over the pudendal nerve, principally from the ventral root of S2. Thus pudendal nerve block does not affect function of the intrinsic striated sphincters; it only halts the activity of the periurethral striated sphincter and the pelvic floor.
Sensation from the striated musculature of the urethral sphincters travels through the pudendal nerves via S2, and to a lesser extent S3, to be correlated centrally in the node of Onuf.
b) Periurethral muscle of the levator system
The periurethral striated sphincter is formed from the medial portions of the pubococcygeus. It is distinct from the prostatic and membranous striated sphincters neurologically and also anatomically, being separated from the membranous urethral sphincter by a continuous connective tissue septum.
19 The muscle fibers are a mixture of slow and fast twitch. Many are of greater diameter than those of the more proximal sphincters and contain the larger Type II fast-twitch fibers. These fibers increase the force and speed of closure when they are recruited to assist the prostatomembranous sphincter during coughing and straining and during voluntary cessation of micturition. The majority of fibers, however, are slow-twitch fibers that are concerned with the tone required to maintain elevation of the prostate, bladder, and rectum so that the other sphincteric mechanisms may be effective. This is the main function of the periurethral striated sphincter in combination with the rest of the pubococcygeus and other parts of the levator ani. This function accounts for the continuous background electromyographic activity obtained from the pelvic floor, activity that ceases before voiding. Voluntary relaxation of the pubococcygeus lowers the prostate and bladder and acts as the signal for reflex contraction of the detrusor. Voluntary contraction will stop urination and reverse detrusor contraction. Reflex elevation occurs during straining and coughing. In addition, the periurethral muscle acts as a sphincter, supplementing the action of the striated prostatic sphincters in maintaining urethral closure.
The periurethral striated sphincter, as part of the levator ani system, is innervated principally from the ventral root of spinal nerve S2 by the pudendal nerve.
The difference in the nerve supply to the prostatomembranous and the periurethral striated sphincters has implications for the determination of striated sphincter activity during the evaluation of candidates for a bladder pacemaker. Incorrect interpretation of electromyograms results when electrodes are not placed accurately within the prostatic striated sphincter.
20
2.2.3 INNERVATION OF THE URINARY SPHINCTERS Autonomic nerves
The nerves to the smooth muscle of the preprostatic sphincter and the prostatic smooth musculature are supplied by sympathetic spinal nerves L2 and L3, passing through the ganglia of the sympathetic chain and along the third and fourth lumbar splanchnic nerves to the superior hypogastric plexus and the right and left hypogastric nerves. These are preganglionic neurons that synapse with short alpha-adrenergic sympathetic postganglionic nerves whose cell bodies lie in the pelvic (inferior hypogastric) plexus lateral to the rectum, bladder, prostate, and seminal vesicles.
Fig. 7 Somatic nerves
The nerves to the striated prostatic and membranous sphincters come from spinal nerves S2 and S3 in branches of the pelvic (splanchnic) nerve through the pelvic plexus. Nerve supply to the periurethral striated sphincter (pubococcygeus) arises from spinal root S2 and runs in the pudendal nerve.
21
2.3 URINARY CONTINENCE [2]
Urine is held at the bladder neck by the internal vesical sphincter under noradrenergic sympathetic control. It is probable that some of the longitudinal fibers of the urethral smooth muscle are similarly innervated. With loss of the bladder neck musculature, as occurs after prostatic resection, the circular smooth muscle of the urethra, also controlled by noradrenergic nerves, contracts to act as the passive sphincter. The prostatomembranous sphincter contains both slow-twitch and fast-twitch fibers, the slow-twitch fibers allowing somatic innervation to act somewhat passively. The periurethral striated sphincter is somatically innervated and provides for voluntary cessation of urination.
A continence function can be ascribed to each of these sphincteric mechanisms. In addition, a vesical neck system that is continuous with the preprostatic sphincter may play a role in maintaining continence at the bladder neck. Even though, structurally, the vesical neck sphincter system is not a true sphincter, it is observed to function to hold the urine at that level, at what is commonly called the “internal sphincter.” It is composed of smooth muscle and elastic fibers that compress the soft mucosal lining together for continence. The tone in this “sphincter,” along with that of the preprostatic sphincter, increases reflexly through noradrenergic sympathetic stimulation as the bladder fills. The function of this complex is to maintain continence at the vesical neck and to prevent retrograde seminal ejaculation.
The prostatomembranous striated sphincter apposes the anterior to the posterior wall of the prostatic urethra, providing more effective sphincteric action of the membranous portion. This mechanism works in concert with the periurethral striated sphincter of the pelvic floor that is actuated by the levator ani system. Contraction of the pelvic floor not only raises the bladder base and lengthens the urethra, but probably also constricts the membranous urethra. Contracting it also blocks bladder contractions by reflexively inhibiting the detrusor motor nucleus through pelvic short neurons. Volitionally relaxing the pelvic floor initiates a reciprocal detrusor contraction.
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3. SURGICAL ANATOMIC AND FUNCTIONAL
CONSIDERATIONS
The main advantages of RARP are ease of pelvic access without a significant pelvimetry issue, a relatively dry field due to venous tamponade afforded by carbon dioxide intraperitoneal insufflation, and magnified view in the range of 10x and surgical instruments with microarticulations near the tip that can duplicate motions of the human hand with 7 degrees of freedom. This advantages bring the surgeon very close to the relevant surgical anatomy, but the admonition of Walsh still holds: “You only see what you are looking for and you only look for what you know” [3]. It is therefore of outmost importance to correlate the anatomical description previously provided with the actual intraoperative view.
3.1 THE ANATOMICAL CONCEPT
It is noteworthy that the bladder does not form a sphincter of its own from its musculature. Rather, it is formed exclusively by the urethra. Also, irrespective of all different views about the anatomy of the urethral sphincter complex there has been complete agreement that it is composed of 2 morphologically related but functionally unrelated components, namely an inner lissosphincter of smooth muscle and an outer rhabdosphincter of skeletal muscle. The urethral sphincter complex extends in the form of a cylinder around the urethra from the vesical orifice to the distal end of the membranous urethra. While the outer component of skeletal muscle is most marked and thickest around the membranous urethra, and becomes gradually less distinct toward the bladder, in contrast, the inner component of smooth muscle has its main part at the vesical orifice and is thinner in its further course in the urethra. Also, whereas the lissosphincter forms a complete cylinder of circular and longitudinal muscle fibers around the urethra, the rhabdosphincter does not. From the perineal membrane to the prostatic apex the skeletal muscle fibers unite behind the urethra in a central fibrous raphe, while more proximal they form a cap on the anterolateral side of the prostate [4].
With high magnification (Fig. 9) and under microscopic vision (Fig. 10) we can clearly recognize 3 layers of musculature at the prostatomembranous urethra: the
23 rhabdosphincter, circular smooth muscles and longitudinal smooth muscles [1]. The ventral part of the sphincter is covered by the dorsal vascular complex and ridges of rudimentary striated muscle fibres (detrusor apron), and the lateral and posterior aspects are surrounded by the apex and neurovascular tissue [5]. The rhabdosphincter sometimes invades the pseudocapsule of the prostate or between the glandular tissues at the apex. Thus, dissection in this area can cut into the apex of the prostate. In addition, some anatomical points to be noted while dissecting the apex include lack of a capsule-like structure in the apex, variation in the form of the prostatic apex and variation in the structure of the sphincter complex in the apex [1].
Fig. 9: Intraoperative view demonstrating the rhabdosphincter (light blue), circular smooth muscles (dark blue), longitudinal smooth muscles (red) and urethral mucosa (yellow).
Fig. 10: Microscopic view showing the rhabdosphincter (RH), circular smooth muscles (CSM), longitudinal smooth muscles (LSM).
recognized with high magnification (Fig. 7). To balance oncological and continence outcomes, the urethra at the apex should be clearly distinguished and meticulously dis-sected. The anatomical morphology of the male rhab-dosphincter reportedly shows interindividual variation.81In
aged males, the posterior rhabdosphincter has thinned or is absent in most cases. The rhabdosphincter sometimes invades the pseudocapsule of the prostate or between the glandular tissues at the apex.82Thus, blunt dissection in this
area can cut into the apex of the prostate. In addition, some anatomical points to be noted while dissecting the apex include lack of a capsule-like structure in the apex,45,83
vari-ation in the form of the prostatic apex84and variation in the
structure of the sphincter complex in the apex.65
The DVC should be ligated to prevent intraoperative blood loss in open prostatectomy. However, if the DVC is bunched and ligated before transection, a form of the
rhab-dosphincter deviates and apical dissection seems to become complicated. A method in which sharp transection of the DVC is carried out before ligation was recently reported for RALP. This method is associated with a decreased apical margin-positive rate and earlier return of postoperative continence.85,86
Problems to be solved in the future The appearance of LRP and RALP allowed for precise rec-ognition of the structures related to radical prostatectomy. Furthermore, the anatomical understanding of nerves, fascias and muscles around the prostate has recently made great progress. Membranes that were previously believed to be single or double-layered were proven to be multilay-ered structures. However, even with highly magnified vision, it is still impossible to confirm autonomic nerves in terminal branches during the operation. Thus, more detailed anatomical knowledge is required. The routes of nerves involved in erection and micturition have not been fully elucidated, and the roles of nerves running around the prostate must be clarified from an anatomical viewpoint. Further discussion on appropriate case selection and opera-tive methods is necessary. In addition, studies involving intraoperative visualization of nerves or cancer sites should also be desired. Tewari et al. reported preclinical applica-tion of multiphoton microscopy as a tool for intrasurgical identification of periprostatic structures.87 Further
physi-ological or intraoperative imaging study should also be encouraged.
Conflict of interest None declared.
References
1 Schuessler WW, Schulam PG, Clayman RV, Kavoussi LR. Laparoscopic radical prostatectomy: initial short-term experience. Urology 1997;50: 854–7.
2 Binder J, Kramer W. Robotically-assisted laparoscopic radical prostatectomy. BJU Int. 2001;87: 408–10.
3 Menon M, Shrivastava A, Tewari A et al. Laparoscopic and robot assisted radical prostatectomy: establishment of a structured program and preliminary analysis of outcomes.
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(a) (a) (b) (b) (a) (b) DVCDVC CSM CSM Prostate Prostate Rectum Rectum LA LA CSM CSM DVC DVC LA LA LSM LSM RH RH LSM LSM RH RH DVC CSM Prostate Rectum LA CSM DVC LA LSM RH LSM RH
Fig. 7 Apex of the prostate. (a) Transverse section.
Masson-trichrome staining. The urethral sphincter complex comprises three layers: the RH, CSM and LSM. (b) Intraoperative view. RH, CSM and LSM are clearly distinguished.
Anatomy for radical prostatectomy
© 2012 The Japanese Urological Association 267
14 R.P. Myers
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Eichelberg C, Erbersdobler A, Michl U et al (2007) Nerve distribution along the prostatic capsule. Eur Urol 51:105–110
Epstein JI (2001) Pathologic assessment of the surgical specimen. Urol Clin North Am 28:567–594 Federative Committee on Anatomical Terminology (1998)
Terminologia anatomica: international anatomical ter-minology. Thieme, Stuttgart
Ganzer R, Blana A, Gaumann A et al (2008) Topographical anatomy of periprostatic and capsular nerves: quanti fi cation and computerised planimetry. Eur Urol 54:353–360
Gil Vernet S (1968) Morphology and function of vesico-prostato-urethral musculature. Canova, Treviso Hollabaugh RS Jr, Dmochowski RR, Steiner MS (1997)
Neuroanatomy of the male rhabdosphincter. Urology 49:426–434
a b
c
Fig. 1.13 Urethral stump, axial section. ( a ) Striated sphincter ( red ) around membranous urethra with circum-ferential smooth muscle (Masson trichrome). ( b ) Urethral
mucosal “seal” from mucosal invaginations (Masson trichrome). ( c ) Signi fi cant elastic tissue ( black ) within membranous urethra (elastic tissue stain)
24
Anatomic and functional studies have shown that the length of the functional urethra is in the range of 1.5–2.4 cm and that a considerable part is located intraprostatically between the prostatic apex and the colliculus seminalis. The prostate develops from the urethra and grows into the overlying striated sphincter muscle, later overgrowing the anterior portion of the urethra and the associated sphincter muscle. At the onset of puberty, the developing prostate further invades the sphincter muscle while overlying some of the sphincter and incorporating it within the prostatic perimeter, resulting in an intraprostatic and extraprostatic portion of the striated sphincter. It is important to note that the apical prostate shape varies significantly. As a result, depending on the individual apex shape, between 10% and 40% of the functional urethra is covered by parenchymal apex tissue among individuals (Fig. 11). To preserve the maximum length of the functional urethra, these anatomic variations have to be considered during individualised preparation of the apical structures. Therefore, it is important to know that because of the above-mentioned developmental processes, the functional parts of the intraprostatically located urethra are not intergrown with the prostatic parenchyma. By thorough anatomic preparation strictly along anatomic landmarks, the intraprostatically located structures of the sphincter can be appropriately and safely separated from the surrounding prostatic tissue without the need for sharp dissection [5].
Fig. 11: The anatomical morphology of the male rhabdosphincter reportedly shows interindividual variation.
25
3.2 THE PHYSIOLOGICAL CORRELATE
Passive Continence by the Lissosphincter [4]
There is good reason to believe and much evidence to show that passive continence is primarily and exclusively a function of the urethral lissosphincter:
1) Urine is normally held at the level of the vesical orifice, which is a smooth muscle function. Also, after transurethral prostatectomy urine is held at the lower limit of the prostatic cavity, where the lissosphincter is intact, and well proximal to the membranous urethra, where the main part of the rhabdosphincter is located.
2) Post-prostatectomy incontinence results from resecting a few mm in depth distal to the verumontanum, which obviously injures the lissosphincter but leaves the more distal rhabdosphincter intact.
3) After posterior anastomotic urethroplasty, which includes excision of the main part of the rhabdosphincter, continence is achieved only by the bladder neck and supramontanal urethra, where the proximal part of the lissosphincter is located, and only scattered and insignificant striated muscle fibers are present.
4) There is no effect on passive continence after rhabdosphincter paralysis by curare injection.
All of this evidence leads to the inescapable conclusion that continence at rest primarily depends on the lissosphincter. On the other hand, the presence of the rhabdosphincter does not guarantee continence and its loss does not cause incontinence in the presence of an intact lissosphincter. The lissosphincter maintains continence at rest by contraction of its muscle fibers, resulting in closure of the vesical orifice and concentric narrowing of the posterior urethra. Maximum closure may be assumed to be at the level of the vesical orifice, where the lissosphincter is most thick, and in the membranous urethra, where the urethra is most narrow. The presence of the whole length of the lissosphincter is not essential to maintain continence. This may be accomplished by the proximal or the distal part of the sphincter alone, as demonstrated in patients after posterior urethroplasty or prostatectomy, respectively. Of course, a minimal length of lissosphincter is crucial for this function, below which incontinence is inevitable. This length is suggested
26
to be more than 1.5 cm.
Genitourinary Function of the Rhabdosphincter [4]
The rhabdosphincter has a dual genitourinary function. The arrangement of muscle fibers in its caudal and cranial parts determines the urinary and genital roles, respectively. The attachment of the caudal part of the muscle to its posterior median raphe would result in movement of the anterior urethral wall toward the posterior wall with contraction. Denonvilliers’ fascia and the rectourethralis muscle together form a relatively rigid posterior plate, against which compression of the pliable anterior urethral wall produces a transversely flattened urethral lumen. This results in a larger surface area of coaptation than could be achieved by concentric contraction of the lissosphincter, thus, creating much higher urethral resistance. This forceful occlusion of the urethra is the principle of active continence, such as that which occurs during events of increased intra-abdominal pressure or during voluntary interruption of micturition. This is confirmed by the finding that it is a mixed slow and fast twitch striated muscle with fast twitch fibers more predominant in the caudal part of the sphincter.
The arrangement of the muscle fibers of the prostatic rhabdosphincter, whether as a distinct muscle cap in children or as indistinctly scattered fibers in adults, would prohibit it from having a significant role in urinary continence. Contraction of this part of the rhabdosphincter would only produce side-to-side compression of the prostatic urethra, which is not sufficient to produce continence but could result in antegrade propulsion of semen in the presence of a closed vesical orifice. Accordingly the prostatic rhabdosphincter has essentially a sexual function.
To summarize, in the light of the aforementioned observations, we can conclude that:
1) Continence at rest is primarily a function of the lissosphincter.
2) An intact rhabdosphincter does not guarantee continence and its absence does not produce incontinence in the presence of an intact lissosphincter. 3) The whole length of the urethral sphincter is not essential to maintain
27 4) A minimal length of the urethral sphincter complex is essential to maintain continence, below which incontinence is inevitable. This length is suggested to be more than 1.5 cm.
5) The main urinary function of the rhabdosphincter is to maintain continence during stress conditions.
All these considerations therefore confirm the great importance of preservation of urethral length at the time of radical prostatectomy in order to preserve continence. Preservation that has to be invariably weighted against the need to avoid positive surgical margins: we need not to forget that radical prostatectomy is in first place an oncological procedure.
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3.3 CONTRIBUTING FACTORS IN POST-PROSTATECTOMY
INCONTINENCE
The preservation of urinary continence is a fundamental goal for patients undergoing radical prostatectomy. The natural history of urinary function recovery after RP is such that most patients regain urinary continence within the first year, however, modest improvement in urinary continence can still be observed through the second year [6].
In a 2012 systematic review and meta-analysis of more than 8000 men who underwent RARP, laparoscopic prostatectomy, or retropubic prostatectomy, for a ‘‘no pad’’ definition of urinary continence, rates of incontinence at 1 year have been shown to range from 4% to 31%, with a mean of 16%. Age, body mass index (BMI), comorbidity index, lower urinary tract symptoms (LUTS), and prostate volume were the most relevant preoperative predictors of urinary incontinence. Regarding operative predictors, surgeon experience, surgical technique, nerve-sparing procedures, bladder neck preservation, preservation of anterior urethral ligaments, urethral length, and proper urethrovesical reconstruction were the most relevant factors [7].
A 2016 review of 128 articles gives an in-depth insight of the contributing factors in post-prostatectomy incontinence (PPI) [6]:
1) Pre-existing LUTS: pre-RP baseline continence is a significant predictor of post-RP continence.
2) Age: older patients are expected to have pre-existing LUTS before RP because of an enlarging prostate and/or age-related functional changes in the urinary bladder and urethra. Patients who recovered their continence 1 year after surgery are significantly younger than patients in the incontinent group.
3) BMI: higher BMI is an independent predictor of worse continence outcomes at 6 and 12 months follow-up.
4) Urethral sphincter complex: the internal sphincter maintains continence during normal activity when there is little stress on the bladder outlet. Its smooth muscle maintains tone for long periods with minimal exertion. The external urethral sphincter is a muscle that is very strong but becomes
29 fatigued very quickly. The action of the external urethral sphincter is often seen when performing cystoscopy after RP and asking the patient to contract. The ability of a patient to circumferentially coapt the urethra on command implies that the muscle tissue and innervations are intact and no hampering fibrosis is present. The two-component model of the urethral sphincter also explains why techniques to spare the bladder neck lead to higher continence rates. Sparing the bladder neck is thought to preserve the majority of the internal sphincter. Preserving this part of the sphincter complex, which is responsible for passive continence, results in earlier return to continence and lower rates of PPI.
5) Supporting structures of the membranous urethra:
a. The anterior urethral support structures contain the pubourethral ligaments, comprising the pubovesical ligament (PVL), the puboprostatic ligament (PLL), and the tendinous arch of the pelvic fascia.
b. The posterior support consists of the perineal body (central perineal tendon), Denonvillier’s fascia, the rectourethralis muscle, and the levator ani complex.
c. The third support structure is the pelvic floor, composed of the levator ani muscle and the surrounding fascia.
It is postulated that the overall role of the support structures is to provide all-round stability and suspensory support for the urethral sphincter complex. Normally the omega-shaped urethral rhabdosphincter has its anchoring points dorsally at the so-called conjoined fibrous tissue. This conjoined fibrous tissue acts like a fulcrum for the anterior forces exerted by the rhabdosphincter. It compresses the urethra in an anteroposterior direction. If the prostate is dissected, attempts to restore these anchoring properties are generally made to allow proper sphincter functioning. This is usually in the form of puboprostatic ligament–sparing or a stitch to anchor the dorsal venous complex. Reconstruction of the posterior musculofascial plate of Denonvilliers or the posterior fibrous raphe, also known as the Rocco stitch seems to improve PPI [8]. It also relieves tension on the
30
anastomosis and improves mucosal coaptation at the anastomosis site. There has been much recent debate about the so-called hypermobility of the bulbous urethra that causes PPI and the restoration of continence by correction of this hyper-mobility and repositioning of the bulbous urethra in males. This is analogous to the hammock theory for women
6) Neural component: a prospective study from Studer shows that neurovascular bundle preservation may improve the chance of remaining continent after open RRP. Incontinence was found in 13.7% of patients without, in 3.4% with unilateral and only in 1.3% with bilateral nerve sparing. The proportional differences were highly significant in favor of a nerve sparing technique (p 0.0001). The precise mechanism behind the functional relationship between nerve sparing and continence remains elusive and it is most likely multifactorial. Neurovascular bundle preservation may influence continence not only by maintaining efferent, but also afferent innervation. The effect of autonomic innervation on the sphincteric mechanism was convincingly shown by intraoperative stimulation of the neurovascular bundle during open RRP. This results in significant increases in urethral pressure. In addition to the efferent autonomic and somatic nerve fibers innervating the sphincteric musculature, intrapelvic afferents from the membranous urethra contribute to urinary continence. Intact proximal sensation leads to improved urinary continence due to a conscious or unconscious sensation of urine entering the membranous urethra. This induces a spinal reflex or voluntary sphincter contraction, resulting in increased tone of the external urethral sphincter and pelvic floor. These afferent nerve fibers from the membranous urethra are postulated to run in branches of the pelvic plexus and/or intrapelvic pudendal nerve, which are prone to iatrogenic damage during radical pelvic surgery. To successfully achieve nerve sparing it is of the utmost importance to minimize trauma to the neurovascular bundle by coagulation, pulling, squeezing or tearing during surgery. Early mobilization along the lateral aspect of the prostate and descending mobilization before transection of the urethra allow better discrimination at the apex than retrograde preparation.
31 Another crucial factor is preservation of the urethral sphincter, without which nerve sparing is of little or no avail [9].
7) Prostate size and membranous urethral length: urethral length preservation during RP improves continence outcomes. In patients with a large prostate, RP is theoretically associated with excision of relatively longer parts of the urethra, which might impact continence outcomes. The 6-months post-RP continence rate was significantly lower for men with prostate size >75 ml than for those with prostate size <75 ml. The continence rates equalized across all prostate size categories at 24-months follow-up. The group of Tewari observed that longer urethral length is significantly associated with quicker postoperative recovery of continence. Longer preoperative and postoperative length was also associated with higher continence rates. Preoperative urethral sphincter length measured with MRI is approximately 14 mm. The continence rate at 6 months in the shorter sphincter group (less than 14 mm) was 47% for the control technique, 81% for anterior reconstruction and 90% for total reconstruction. The continence rate in the longer sphincter group (more than 14 mm) was 80% for the control technique and 83% for anterior reconstruction, while it approached 99% for total reconstruction. With the control technique the average time to achieve continence was significantly different between the shorter and longer sphincter groups (25 vs 12 weeks). Continence recovery at 1 year was 89% among patients with urethral length >12mm postoperatively, compared to 77% for patients with urethral length <12 mm [10].
8) Fibrosis: incidence of fibrosis is much greater in patients with PPI than in patients without.
9) Urothelium: at the junction of the inferior bladder and the proximal urethra, the urothelium becomes a key component of sphincter function. The elastic components of the proximal urethral wall are responsible for coaptation of the urothelium (zone of coaptation). This proper adhesion of the urethral wall provides primary resistance to the urine to maintain continence. Little is known about the optimal length of the zone of coaptation. It is hypothesized that it should be at least 5–10 mm to ensure continence.
32
10) Functional bladder changes: functional changes including detrusor overactivity and reduced compliance may develop after RP due to denervation or devascularization of the urinary bladder. Some findings also attributed the deterioration in storage symptoms among their patients to a reduction in maximum cystometric capacity.
11) TURP before RP: PPI incidence is up to 50% among men who underwent TURP 4 weeks to 4 months before RP. It has been recommended to wait 4 months after TURP prior to RP.
33
4. ROBOT-ASSISTED RADICAL PROSTATECTOMY
4.1 THE RISE OF ROBOTIC SURGERYThe years since the turn of the millennium have seen unprecedented infiltration of technology into daily life. In urology this change has been punctuated with the widespread adoption of robot-assisted surgery. At the time that he published his landmark paper, Clement-Claude Abbou was chairman of Urology at the Henri Mondor Hospital in Creteil, a suburb of Paris, and a gifted laparoscopic surgeon. Binder and Kramer, two German urologists, had previously performed robotic prostatectomy albeit with ports placed through a small laparotomy but had not yet published their results. Abbou thought he could incorporate the robot into the laparoscopic procedure which he had already performed with remarkable success. Borrowing a da Vinci robot from cardiac surgery, he performed the world’s first complete robot-assisted radical prostatectomy, reporting this first in the French journal, Progres en Urologie, and subsequently in The Journal of Urology. At the time, there were fewer than 10 robots in the world, all in cardiac surgery, and a single mobile robot that was moved from center to center in Europe exploring the use of robotics in other surgical disciplines. Abbou’s work inspired Rassweiler in Germany and Vallancien in Paris to perform small case series of robotic prostatectomies with the mobile da Vinci system. The next several years saw collaborative efforts from teams on both sides of the Atlantic. In September 2000 Menon was in Paris exploring ways in which he could establish a laparoscopic prostatectomy program in Detroit with the collaboration of the French surgeons. Abbou, Vallancien and Menon met at La Cloiserie des Lilas in Paris, a restaurant once frequented by the likes of Cezanne, Hemingway, Picasso and Sartre (prophetically Abbou picked the location). Over lunch, Abbou and Vallancien suggested that Menon consider incorporating robotic assistance into his planned laparo- scopic prostatectomy program. Not that Menon required much persuasion. He considered himself laparoscopically challenged and the gifted laparoscopic surgeons who had attempted laparoscopic prostatectomy in the United States had reported somber results. To Menon, the robot seemed to make sense. However, urologists did not have easy access to the technology as all robotic surgical systems
34
installed in the U.S. were housed in departments of cardiac surgery. Menon’s first move was to negotiate the purchase of a da Vinci robot for urology, which he did within 3 days of FDA approval of robotics for abdominal surgery. At Henry Ford Hospital Vattikuti Urology Institute, he created the first structured program in the world for robotic radical prostatectomy. This work had a major role in the rapid expansion of robotic surgery. Building upon the skills learned while developing the robot-assisted radical prostatectomy, the technology was implemented in other areas of urological oncology such as radical cystectomy, partial nephrectomy and renal transplantation [11].
Since publication of Abbou’s paper, the robot-assisted approach has become the dominant mode of surgical removal of the prostate, with more than 85% cases of prostatectomies being nowadays performed robotically (Fig. 12) [12].
Fig. 12
In 2000, before the development of robotic prostatectomy, Intuitive Surgical, the manufacturer of the da Vinci system, was struggling with 18 systems worldwide, largely unused. By now there are more than 3,900 systems (Fig. 13) worldwide and more than 4,000,000 operations performed [13].
35
Fig. 13
The story began with a single operation using a borrowed robot, lunch in a Parisian bistro and a case report in The Journal of Urology. It morphed into a nearly ubiquitious procedure in urology, and has paved the way for technology and surgical innovation in many surgical fields and for many years to come.
“In my opinion, there is no way back from robotic surgery.” Pier Cristoforo Giulianotti, February 2013
36
4.2 OUTCOMES OF ROBOT-ASSISTED RADICAL PROSTATECTOMY 4.2.1 PERIOPERATIVE OUTCOMES
The prospective controlled trial LAPPRO (Laparoscopic Prostatectomy Robot Open) in 2014 compared the short-term results and adverse events in 2506 men following RRP or RARP (778 RRP, 1847 RARP). All patients were operated by experienced surgeons (>100 procedures). The robot-assisted surgery group had less perioperative bleeding (185 vs 683 ml, p <0.001) and shorter hospital stay (3.3 vs 4.1 d, p < 0.001) than the open surgery group. Operating time was shorter with the open technique (103 vs 175 min, p < 0.001) compared with the robot-assisted technique (Fig. 14) [14].
Fig. 14: Comparison of perioperative outcomes of RRP and RARP
Reoperation during initial hospital stay was more frequent after open surgery after adjusting for tumor characteristics and lymph node dissection (1.6% vs 0.7%, odds ratio [OR] 0.31, 95% confidence interval [CI 95%] 0.11–0.90). Men who underwent open surgery were more likely to seek healthcare (for one or more of 22 specified disorders identified pre-study and grouped as: infection, cardiovascular, surgical, gastrointestinal, and psychological) compared to men in the robot-assisted surgery group (p = 0.03). It was more common to seek healthcare for cardiovascular reasons in the open surgery group than in the robot-assisted surgery group, after adjusting for non-tumor and tumor-specific confounders, (7.9% vs 5.8%, OR 0.63, CI 95% 0.42–0.94). The readmission rate was not statistically different between the groups [14].
37
4.2.2 ONCOLOGICAL OUTCOMES
To date there is only one study reporting 10 years long terms outcomes of RARP published in 2015 by the group of Menon, including 483 consecutive men with localized prostate cancer who underwent RARP at a high-volume tertiary center from 2001 to 2003. Biochemical recurrence–free survival (BCRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) were calculated and actuarial rates are estimated via Kaplan-Meier, showing how RARP confers effective 10-years cancer control. There were 108 patients with BCR at a median follow-up of 121 months (Fig. 15, Fig. 16). Actuarial BCRFS, MFS, and CSS rates at 10 years were 73.1%, 97.5% and 98.8%, respectively, results in line with the open RP series. On multivariable analysis, D’Amico risk groups or pathologic Gleason grade, stage, and margins were the strongest predictors of BCR depending on whether preoperative or postoperative variables were considered. The value of the detectable PSA together with disease severity were independent predictors of receipt of salvage therapy, together with a persistent PSA for metastases [15].
Fig. 15: BCRFS based on the postoperative risk group
38 Follow-up months
3 6 9 12 18 24 36 48 60 72 84 96 108 120
Group 1: (mean time = 41.2 months, std. err. = 0.3)
At risk 157 153 152 151 144 143 135 132 127 112 106 93 81 53 Events 1 1 1 1 1 1 2 3 3 3 3 3 3 3 BCRFS probabil ity 0.99 4 0.99 4 0.99 4 0.99 4 0.99 4 0.99 4 0.98 6 0.97 9 0.97 9 0.97 9 0.97 9 0.97 9 0.97 9 0.97 9
Group 2: (mean time = 102.8 months, std. err. = 2.2)
At risk 170 168 167 165 156 153 145 137 128 106 94 84 60 31 Events 2 2 2 3 7 8 9 13 15 19 23 26 26 27 BCRFS probabil ity 0.98 8 0.988 0.988 0.982 0.958 0.952 0.946 0.919 0.905 0.875 0.840 0.813 0.813 0.795
Group 3: (mean time = 85.2 months, std. err. = 4.4)
At risk 108 99 98 96 89 85 80 74 70 52 47 42 30 18 Events 5 7 8 10 15 19 23 28 29 37 37 39 41 44 BCRFS probabil ity 0.95 4 0.93 5 0.92 5 0.90 7 0.85 9 0.82 0 0.78 1 0.73 2 0.72 2 0.63 6 0.62 2 0.60 8 0.57 8 0.50 8
Group 4: (mean time = 54.6 months, std. err. = 7.4)
At risk 48 33 34 32 29 27 24 20 17 14 12 8 5 4 Events 9 13 13 14 17 19 22 25 27 28 30 32 32 33 BCRFS probabil ity 0.80 9 0.72 3 0.72 3 0.70 2 0.63 6 0.59 2 0.52 6 0.46 0 0.41 4 0.39 0 0.33 4 0.27 0 0.27 0 0.21 6
Fig. 16: BCRFS probability according to group stratification (Risk group 1 group corresponds to patients with pT2, Gleason 3 + 3, and negative margins (n = 157). Risk group 2 (n = 170) combines patients with pT2, Gleason 7, and negative margins or pT2, Gleason 6, and positive margins. Risk group 3 (n = 108) combines patients with pT2, Gleason 8, and negative margins or patients with pT2 but Gleason 3 + 4 and positive margins or patients with pT3–pT4, Gleason 3 + 4, independent of margin status. All patients in risk group 4 (n = 48) have primary Gleason 4. In addition, they present pT2 with positive margins or pT3–pT4)
A population based observational cohort study of the SEER-Medicare linked database compared a total of 6.430 robot-assisted radical prostatectomies and 9.161 open radical prostatectomies performed during 2003 to 2012. The use of robot-assisted radical prostatectomy increased from 13.6% in 2003 to 2004 to 72.6% in 2012. After a median follow-up of 6.5-years RARP was associated with an equivalent risk of all-cause mortality and similar cancer specific mortality of open radical prostatectomy (Fig. 17). RARP was also associated with less use of additional treatment [16].
39
Fig. 17: CSS of RRP (light grey) and RARP (black)
Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon's skill. The apex and posterolateral regions are the most common locations for PSM in RRP. Posterolateral margins are often the result of efforts to preserve the neurovascular bundles, as this region broadly describes where intrafascial or interfascial dissection occurs for nerve sparing, and reports
described a greater effect of a posterolateral margin on BCR rates. A
multi-institutional study involving 4,001 RARP patients operated at 3 major treatment centers, prospectively conducted between January 2002 and October 2013, gives us an insight on the prevalence and clinical significance of PSM in RARP. When comparing a PSM with negative margin cases, chi-squared differences revealed a higher preoperative PSA level, smaller prostate volume, and higher stage and grade disease. Overall PSM were found in 486 patients, meaning 12.5% of all cases, with the following location: posterolateral (3.62%), base (0.87%), apical (3.15%), anterior (0.72%) and multifocal (3.12%). 37% of the PSM cases went onto develop BCR compared with just 10% of NSM cases. Multifocal, apical, and posterolateral regions contributed to the greatest number of PSMs (27%, 27%, and 32%, respectively), and the greatest number of BCR among PSM cases. On both the regression analyses, a PSM was associated with a greater risk of BCR relative to a NSM (HR=1.81, 95% CI: 1.47–2.22). Multifocality and a margin length of >3 mm
40
both carry an increased risk of time to BCR compared with NSM. On analysis of the PSM-only cohort, only margin length >3 mm remains a significant predictor of higher recurrence, with a 2.18-fold greater risk of time to BCR compared with margins <3 mm in length (95% CI: 1.34–3.57). On multivariable regression analysis of only the positive margin cohort, apical margins were the only margin location that significantly predicted BCR, with an HR of 2.03 (95% CI: 1.01–4.09) relative to a basal margin; interestingly, posterolateral margins showed no significant difference [17].
A 2015 single institution study comparing the rate of PSMs in a large population of 4,404 patients treated with open RRP (71.1%) or 1,790 RARP (28.9%) found that overall, 1,335 (21.6%) patients had PSMs. The positive margins rate was 291 (16.3%) and 1,044 (23.7%) for patients who underwent RARP and who underwent RRP, respectively (p <0.001). When patients were stratified according to preoperative risk groups, RARP showed a statistically significant lower rate of PSMs in low-risk patients (11.5% vs. 15.4%, P = 0.01) as well as in intermediate-risk patients (18.9% vs. 23.5%, p = 0.008). However, the most benefit of the robotic approach was seen in high-risk patients, where the rate of PSMs in patients treated with RARP was 19.7% vs. 30.1% in patients treated with RRP (p < 0.001) [18]. According to a 2012 meta-analysis the prevalence of PSMs after RARP ranged from 6.5% to 32%, with a mean value of 15%. The mean PSM rate was 9% (range: 4–23%) in pT2 cancers, 37% (range: 29–50%) in pT3 cancers, and 50% (range: 40– 75%) in pT4 cancers. Surgical margins were positive at the prostate apex in 5% (range: 1–7%) of the cases, anteriorly in 0.6% (range: 0.2–2%), at the bladder neck in 1.6% (range: 1–2%), and posterolaterally in 2.6% (range: 2–21%). Finally, multifocal PSMs were detected in 2.2% (range: 2–9%) of the cases. Cumulative analyses showed only non–statistically significant differences in overall PSM rates following RRP and RARP (21% and 20%; OR: 1.21; 95% CI, 0.91–1.63; p = 0.19). Figure 18 shows a forest plot comparing PSM rates in pT2 cancers following RRP and RARP. PSM rates in pT2 cancers were similar following RRP and RARP (12% and 11%; OR: 1.25; 95% CI, 0.81–1.93; p = 0.31) [19].
41
42
4.2.3 INCONTINENCE FOLLOWING RARP
In a 2012 systematic review and meta-analysis of more than 8000 men who underwent RARP, laparoscopic prostatectomy, or retropubic prostatectomy, for a ‘‘no pad’’ definition of urinary continence, rates of incontinence at 1 year following RARP have been shown to range from 4% to 31%, with a mean of 16%. After 24– 36 months, urinary incontinence rates of 5% to 12% have been reported. Age, body mass index (BMI), comorbidity index, lower urinary tract symptoms (LUTS), and prostate volume were the most relevant preoperative predictors of urinary incontinence. Regarding operative predictors, surgeon experience, surgical technique, nerve-sparing procedures, bladder neck preservation, preservation of anterior urethral ligaments, urethral length, and proper urethrovesical reconstruction were the most relevant factors [7].
When comparing RARP with open RRP, the median time to continence in RARP patients was found to be 1.6 months, significantly lower in comparison with the value of 4.3 months reported in the RRP patients (p < 0.001). The cumulative analysis evaluating the 12-months urinary continence recovery after RARP or RRP shows an absolute risk of urinary incontinence of 11.3% after RRP (105 of 923 cases) and 7.5% after RARP (38 of 509 cases), with an absolute risk reduction of 3.8%. For the first time, the present cumulative analysis showed significant advantages for RARP in comparison with RRP in terms of 12-months urinary continence rates (OR: 1.53; 95% CI, 1.04–2.25; p = 0.03) (Fig. 19) [7]. Conversely the LAPPRO trial did not show any difference at 12 months: after RALP, 366 men (21.3%) were incontinent, as were 144 (20.2%) after RRP, with an adjusted OR of 1.08 (95% confidence interval [CI], 0.87–1.34) [20].
43 Interestingly, when comparing posterior reconstruction versus the standard technique, the analyses showed only a small statistical advantage in favor of posterior reconstruction only after 1 month and no influence at 3 and 6 months. Although the impact of posterior musculofascial reconstruction on early continence is possibly less accentuated than initially thought, the technique is simple and 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 [7].
The use of barbed suture was recently proposed with the aim of reducing the time needed to perform the reconstructive steps of the RARP procedure. A 2011 RCT showed that the use of barbed monofilament suture was associated with overlapping urinary continence recovery in comparison with the standard monofilament [21].
