Effect of a Risk-stratified Grade of Nerve-sparing Technique on Early Return of Continence After Robot-assisted Laparoscopic Radical Prostatectomy

Transcription

1 EUROPEAN UROLOGY 63 (2013) available at journal homepage: Platinum Priority Prostate Cancer Editorial by Declan G. Murphy and Anthony J. Costello on pp of this issue Effect of a Risk-stratified Grade of Nerve-sparing Technique on Early Return of Continence After Robot-assisted Laparoscopic Radical Prostatectomy Abhishek Srivastava a, Sameer Chopra a, Anthony Pham a, Prasanna Sooriakumaran a, Matthieu Durand a, Bilal Chughtai a, Siobhan Gruschow a, Alexandra Peyser a, Niyati Harneja a, Robert Leung a, Richard Lee a, Michael Herman a, Brian Robinson b, Maria Shevchuk b, Ashutosh Tewari a, * a LeFrak Institute of Robotic Surgery and Prostate Cancer Institute, James Buchanan Brady Foundation Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA; b Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA Article info Article history: Accepted July 9, 2012 Published online ahead of print on July 20, 2012 Keywords: Prostate cancer Continence Nerve-sparing Robotic-assisted laparoscopic prostatectomy Abstract Background: The impact of nerve sparing (NS) on urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RALP) has yet to be defined. Objective: To evaluate the effect of a risk-stratified grade of NS technique on early return of urinary continence. Design, setting, and participants: Data were collected from 1546 patients who underwent RALP by a single surgeon at a tertiary care center from December 2008 to October Patients were categorized preoperatively by a risk-stratified approach into risk grades 1 4, with risk grade 1 patients more likely to receive NS grade 1 or complete hammock preservation. This categorization was also conducted for risk grades 2 4, with grade 4 patients receiving a non-ns procedure. Intervention: Risk-stratified grading of NS RALP. Outcome measurements and statistical analysis: Univariate and multivariate analysis identified predictors of early return of urinary continence, defined as no pad use at 12 wk postoperatively. Results and limitations: Early return of continence was achieved by 791 of 1417 men (55.8%); of those, 199 of 277 (71.8%) were in NS grade 1, 440 of 805 (54.7%) were in NS grade 2, 132 of 289 (45.7%) were in NS grade 3, and 20 of 46 (43.5%) were in NS grade 4 ( p < 0.001). On multivariate analysis, better NS grade was a significant independent predictor of early return of urinary continence when NS grade 1 was the reference variable compared with NS grade 2 ( p < 0.001; odds ratio [OR]: 0.46), NS grade 3 ( p < 0.001; OR: 0.35), and NS grade 4 ( p = 0.001; OR: 0.29). Lower preoperative International Prostate Symptom Score ( p = 0.001; OR: 0.97) and higher preoperative Sexual Health Inventory for Men score ( p = 0.002; OR: 1.03) were indicative of early return of urinary continence. Positive surgical margin rates were 7.2% (20 of 277) of grade 1 cases, 7.6% (61 of 805) of grade 2 cases, 7.6% (22 of 289) of grade 3 cases, and 17.4% (8 of 46) of grade 4 cases ( p = 0.111). Extraprostatic extension occurred in 6.1% (17 of 277) of NS grade 1 cases, 17.5% (141 of 805) of NS grade 2 cases, 42.5% (123 of 289) of NS grade 3 cases, and 63% (29 of 46) of NS grade 4 cases ( p < 0.001). Some limitations of * Corresponding author. LeFrak Institute of Robotic Surgery and Prostate Cancer Institute, James Buchanan Brady Foundation Department of Urology, Weill Medical College of Cornell University, 525 East 68th Street, Starr 900, New York, NY 10065, USA. Tel ; Fax: address: ashtewarimd@gmail.com (A. Tewari) /$ see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

2 EUROPEAN UROLOGY 63 (2013) the study are that the study was not randomized, grading of NS was subjective, and possible selection bias existed. Conclusions: Our study reports a correlation between risk-stratified grade of NS technique and early return of urinary continence as patients with a lower grade (higher degree) of NS achieved an early return of urinary continence without compromising oncologic safety. # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. 1. Introduction Prostate cancer is the most common nondermatologic cancer affecting men in the Western world [1]. The gold standard primary treatment option for prostate cancer has been open retropubic radical prostatectomy (RP) [2]. However, robot-assisted laparoscopic prostatectomy (RALP) has become more common, with its lower intraoperative and postoperative complication rates [3,4]. The Nationwide Inpatient Sample found that 60% of RPs from October 2008 to December 2009 were robotic assisted [5]. Urinary incontinence is a well-established adverse effect of this procedure and results in a detrimental impact on patients quality of life (QoL) [6]. Return to continence is sensitive to the surgical technique used, including methods that attempt to preserve the neurovascular bundles (NVBs) [7]. Along with preoperative continence and patient age, nerve sparing (NS) has been demonstrated to be a significant predictor of continence outcomes in patients, with usage of an NS technique associated with improved recovery of urinary continence in a small study [8]; however, this association remains to be shown in a large cohort [8 12]. In this study, we evaluated the effect of our risk-stratified grade of NS technique on early return of urinary continence in 1546 consecutive patients. 2. Patients and methods 2.1. Study cohort This is a case series study of 1546 consecutive men who underwent RALP by a single surgeon (A.T.) at a tertiary care center from December 2008 to October 2011; 129 patients were lost to follow-up at 12 wk and were not available for analysis. All included patients were continent preoperatively. Patients were categorized preoperatively by a risk-stratified approach into risk grades 1 4, with risk grade 1 patients more likely to receive NS grade 1 or complete hammock preservation. This categorization was also conducted for risk grades 2 4, with grade 4 patients receiving a non-ns procedure (Fig. 1) [13]. The lead surgeon (A.T.) ultimately decided the NS grade to be performed based on a risk-stratification algorithm and intraoperative visual cues [14]. This system of defining NS grades was introduced in December 2008, and all patients were graded prospectively on the day of surgery after completion of each case by the lead surgeon Data collection Data for clinicopathologic variables such as age, prostate-specific antigen (PSA) level, body mass index (BMI), clinical stage, NS grade, and biopsy and pathology Gleason sums were collected under an institutional review board approved protocol concerning health-related QoL (HRQoL) in patients undergoing RALP at our institution. Continence function at baseline and all follow-up intervals was assessed using the question, How many pads or adult diapers per day did you usually use to control leakage during the last 4 weeks? Continence was defined as the use of no pads per 24 h. All of the patients also received the International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) questionnaires to assess their preoperative urinary symptom score and sexual function, respectively Patient follow-up A follow-up questionnaire was dispatched to patients through either postal or electronic mail at 6 wk and 12 wk after RALP. A member of the research team contacted subjects via telephone to ensure receipt of the questionnaire. A third party, not involved in patient care, performed data collection and follow-up correspondence in compliance with the US Health Insurance Portability and Accountability Act Statistical methods Categorical distributions are reported as counts (percentages) and continuous variables as medians and interquartile ranges. The chisquare test was used to assess differences in distributions among categorical variables. The Kruskal-Wallis test was used to assess differences in distributions among continuous variables. Univariate and multivariate logistic regression models were constructed to identify predictors of early return of urinary continence. All tests were two-sided, with statistical significance set at p < Statistical analysis was performed using IBM SPSS statistics 19.0 (IBM Corp., Armonk, NY, USA) and the statistical package R v (R Foundation for Statistical Computing, Vienna, Austria) Pathologic data collection Dedicated genitourinary pathologists (B.R., M.S.) from our institution examined the pathologic specimens and commented on the presence or [(Fig._1)TD$FIG] Preopera ve decision making Risk Grade 1 Risk Grade 2 Risk Grade 3 Risk grade 4 PSA <4 PSA 4 10 PSA PSA >20 Clinical stage T1 Clinical stage T2a- T2b Clinical stage T2c Clinical stage T3 Gleason 6 Gleason Gleason Gleason 8 Nega ve MRI Visible tumor on emri Suspicious/micro EPE on emri Confirmed/gross EPE on emri Fig. 1 Algorithm for risk-stratified approach to nerve sparing. Prostatespecific antigen levels in nanograms per milliliter. Risk grade 1: All criteria should be met; risk grade 2 4: any two criteria or magnetic resonance imaging (MRI) findings. If MRI findings are not available, only clinical criteria are used. EPE = extraprostatic extension; emri = endorectal magnetic resonance imaging; PSA = prostate-specific antigen. (From [13,14].)

3 440 [(Fig._2)TD$FIG] EUROPEAN UROLOGY 63 (2013) Fig. 2 Histology of non-nerve-sparing radical prostatectomy specimen with wide excision of adjacent tissue. Note the distribution of nerve fibers (highlighted in green) in the periprostatic fascial layers. The collapsible veins on the prostate capsule (outlined in blue) are a distinct anatomic landmark; most of the periprostatic nerve fibers lie lateral to these veins. Notice also the area of extraprostatic extension of cancer through the prostate capsule adjacent to these veins. N = nerve; EPE = extraprostatic extension. (From [13,14].) absence of positive surgical margins (PSMs) and extraprostatic extension (EPE). Our specimen handling and fresh tissue banking protocols have been published previously [15]. involves varying degrees of preservation of the nerve fibers in the various fascial planes (Figs. 2 and 3). They are referred to with the following definitions: 2.6. Surgical technique Our risk-stratified grade of NS technique has been described previously [13]. Visual cues were utilized to aid in NS grading decisions intraoperatively [14]. This approach is based on the patient s likelihood of ipsilateral EPE and has been created to address the competing goals of cancer clearance with preservation of potency. The patient s PSA level, biopsy Gleason score, clinical stage, and findings on the endorectal magnetic resonance imaging (MRI) parameters were used for risk [(Fig._3)TD$FIG] stratification of patients (Fig. 1). Our approach to NS during RALP Grade 1 NS: Incision of the Denonvilliers fascia and the lateral pelvic fascia (LPF) is made just outside the prostatic capsule to preserve the neural hammock. This represents the greatest degree of NS possible, and we perform this procedure for patients with no risk to minimal risk of EPE. Grade 2 NS: Incision through the Denonvilliers fascia (leaving deeper layers on the rectum) and the LPF is made just outside the layer of veins of the prostate capsule. This preserves most large neural trunks and ganglia and is used for patients at low risk of EPE. Grade 3 NS (partial/incremental): Incision is made through the outer compartment of the LPF (leaving some yellow adipose and neural tissue on the specimen), excising all layers of Denonvilliers fascia. This is performed for patients with moderate risk of EPE because some of the medial trunks are sacrificed, whereas the lateral trunks are preserved. Grade 4 NS (non-ns): These patients have high risk of EPE and are not candidates for NS. In such cases, we perform a wide excision of the LPF and Denonvilliers fascia containing most of the periprostatic neurovascular tissue. In selected patients, we attempt nerve advancement of the identifiable ends of the NVBs [16]. Patients with different NS grades on each side of the prostate are classified according to the higher NS grade (lesser NS) of the two in the present study. 3. Results Fig. 3 Layers of fascia enveloping prostatic capsule, demonstrating the planes of dissection for differing grades (1 4) of nerve sparing. LPF = lateral pelvic fascia; LF = levator fascia; LA = levator ani. (From [13,14].) Baseline demographics, clinical data, and pathologic data for each of the NS grades are summarized in Table 1. We compared the four grades of NS and documented whether

4 EUROPEAN UROLOGY 63 (2013) Table 1 Baseline demographics and clinical and pathologic data of 1417 patients Variable No. of patients (n = 1417) NS grade 1 (n = 277) NS grade 2 (n = 805) NS grade 3 (n = 289) NS grade 4 (n = 46) p value Age, median (IQR) 60 (55 65) 59 (53 63) 60 (55 65) 62 (56 67) 63 (56 66) <0.001 BMI, median (IQR) 27 (25 29) 26 (24 28) 27 (25 29) 27 (25 30) 26 (24 29) Preoperative PSA, median (IQR) 4 (5 7) 4 (3 6) 5 (4 6) 5 (4 8) 7 (4 10) <0.001 Preoperative IPSS, median (IQR) 7 (3,12) 6 (3 11) 7 (3,11) 6 (3 12) 7 (4 15) Preoperative SHIM, median (IQR) 23 (15 25) 24 (19 25) 22 (16 25) 21 (10 25) 22 (13 25) <0.001 Clinical stage, % <0.001 T T T Biopsy Gleason, % < Prostate volume, median (IQR) 47 (38 59) 45 (35 56) 47 (38 58) 49 (40 63) 48 (40 63) Pathology Gleason, % < Pathology stage, % <0.001 T T PSM, % BMI = body mass index; IPSS = International Prostate Symptom Score; IQR = interquartile range; NS = nerve sparing; PSA = prostate-specific antigen; PSM = postivie surgical margin; SHIM = Sexual Health Inventory for Men. Table 2 Continence and pathology outcomes data in our cohort Variable NS grade 1 (n = 277) NS grade 2 (n = 805) NS grade 3 (n = 289) NS grade 4 (n = 46) p value Baseline continent, no. (%) 277 (100) 805 (100) 289 (100) 46 (100) Early continence, no. (%) 199 (71.8) 440 (54.7) 132 (45.7) 20 (43.5) <0.001 PSM rate, no. (%) 20 (7.2) 61 (7.6) 22 (7.6) 8 (17.4) EPE rate, no. (%) 17 (6.1) 141 (17.5) 123 (42.7) 29 (63.0) <0.001 EPE = extraprostatic extension; NS = nerve sparing; PSM = positive surgical margin. early continence was achieved (Table 2). Overall, 791 of 1417 patients (55.8%) in the study achieved early continence. There was a statistically significant difference across the different NS grades for the percentages of patients who achieved early continence postoperatively ( p < 0.001). Early continence was achieve by 199 of 277 (71.8%) NS grade 1 patients, 440 of 805 (54.7%) NS grade 2 patients, 132 of 289 (45.7%) NS grade 3 patients, and 20 of 46 (43.5%) NS grade 4 patients. We performed a univariate and multivariate analysis with known predictors of postoperative continence outcomes such as age, BMI, preoperative IPSS, preoperative Table 3 Univariate and multivariate analysis of early continence outcomes Univariate analysis Multivariate analysis OR (95% CI) p value OR (95% CI) p value Age 0.96 ( ) < (0.96 1) BMI 1 (1 1.01) (1 1.01) Preoperative IPSS 0.96 ( ) < ( ) Preoperative SHIM 1.05 ( ) < ( ) Prostate volume 0.99 ( ) < (0.99 1) NS grade (ref) 1.00 (ref) ( ) < ( ) < ( ) < ( ) < ( ) < ( ) BMI = body mass index; CI = confidence interval; IPSS = International Prostate Symptom Score; NS = nerve sparing; OR = odds ratio; SHIM = Sexual Health Inventory for Men.

5 442 EUROPEAN UROLOGY 63 (2013) SHIM, prostate volume, and grades of NS [7,12,17 22]. We did not include disease characteristics in the multivariate analysis shown, as it directly affects the choice of NS performed. These results are summarized in Table 3. On multivariate analysis, better NS grade was a significant independent predictor of early return of urinary continence when NS grade 1 was the reference variable compared with NS grade 2 ( p < 0.001; odds ratio [OR]: 0.46), NS grade 3 ( p < 0.001; OR: 0.35), and NS grade 4 ( p = 0.001, OR: 0.29). Lower preoperative IPSS score ( p = 0.001; OR: 0.97) and higher preoperative SHIM score ( p = 0.002; OR: 1.03) were marginally predictive of early return of urinary continence. PSM rates in grades 1 4 were 7.2% (20 of 277), 7.6% (61 of 805), 7.6% (22 of 289), and 17.4% (8 of 46), respectively ( p = 0.111). EPE occurred in 6.1% (17 of 277), 17.5% (141 of 805), 42.5% (123 of 289), and 63% (29 of 46) of cases that underwent NS grades 1 4 ( p < 0.001). 4. Discussion Studies demonstrate that the distribution of the NVB is more complex than previously described by Walsh and Donker [2], with Tewari et al. describing the presence of smaller nerves surrounding the prostate located in the periprostatic space and Denonvilliers fascia [23]. Additional studies described a hammock-like distribution of the nerves on which the prostate rests [24 28] as well as a more complex course of fibers of the NVB found beyond the typical distribution at the rectolateral side of the prostate along the ventral circumference of the prostate [29]. Collectively, these studies have changed the view of the cavernous nerves from an NVB to a network of multiple, finely dispersed nerves. Surgical techniques were developed to preserve lateral prostatic fascia in the anterolateral zones [30]. Recently, modalities such as three-dimensional computer-assisted anatomic dissection have provided detailed knowledge of the distribution and distal course of periprostatic nerves to improve functional outcomes after RP [31]. The mechanism for the functional relationship between NS and continence is unclear and is likely to be multifactorial. Both efferent and afferent nerves of the NVB may function in continence restoration. The impact of autonomic innervation on the urethral sphincter was demonstrated by intraoperative stimulation of the NVB; this resulted in a significant increase in urethral pressure [32]. Intact proximal sensation can improve urinary continence by the sensation of urine entering the membranous urethra, causing a spinal reflex or voluntary contraction of the sphincter that will increase the tone of the external urethral sphincter and the pelvic floor [9]. This supports the belief that there is an association between an NS procedure and recovery of urinary continence [33]. Minimal data shows the role of cavernous neural preservation on early recovery of continence. We hypothesize that cavernous nerve preservation contributes to the multifactorial mechanism for the functional relationship between NS and continence. Our study evaluates the impact of risk-stratified grade of NS technique on the early return of urinary continence after RALP. We defined early continence as those patients who used no pads at or before the end of postoperative week 12. In 1546 patients, 55.8% of men achieved early continence and NS technique was an independent predictor of early return of urinary continence. These results support those of prior studies that suggest that NS improves recovery of urinary continence [12,34 39]. A study conducted on 265 patients in 2007 demonstrated that NS and preoperative erectile function led to an earlier return of urinary continence, but the authors did not clarify the number of surgeons performing the procedures, making surgeon experience a confounding problem [40]. A similar study of 135 patients demonstrated the importance of NS on continence and emphasized the importance of preoperative erectile function as a predictor for postoperative urinary continence [41]. This study categorized NS as either bilateral or unilateral. In 2010, Kalble et al. demonstrated that patients who underwent their NS technique were more likely to regain urinary continence than the non-ns group [42]. Our study not only confirmed these findings but showed that the greater the degree of NS, the greater the likelihood of early return to continence. Our study also showed that this could be achieved without compromising PSM rates. A recent study investigated predictors that have an impact on postoperative urinary continence after NS RP and found that patient age and preoperative erectile function predict return of urinary continence after NS RP [17]. Age as a predictor of early recovery of urinary continence has also been confirmed in other studies [18 20]. Wei et al. found a significant interaction of nerve sparing with patient age and the effect of nerve sparing, with nerve sparing being more effective in younger patients [12]. Our study has also demonstrated that fewer urinary symptoms and better erectile function preoperatively are independent predictors of return of early continence. In 2012, Ko et al. determined factors that affected the return to early continence after RALP [33]. They identified preoperative and intraoperative factors responsible for continence return. This study had a large sample size of 1299 patients who underwent RALP by a single surgeon. This study concluded that patient age and degree of NS were independent predictors of the return of early continence but found no notable difference when time to recovery was compared between partial NS and bilateral NS. Surgical technique may influence continence. In addition to age and degree of neurovascular resection, Eastham et al. found that surgical technique and anastomotic stricture were significant risk factors for urinary incontinence [7]. It has been shown that functional outcomes can be affected by a learning curve after the adoption of new surgical techniques [43]. In our own cohort, all patients received a total reconstruction technique. Within this cohort, slight surgical variations or modifications of the technique such as retroapical technique or use of barbed suture have not made any difference in continence outcomes (data not shown). Moreover, we are not comparing overall outcomes from before the adoption of the NS grading system and afterward, so the effect of the surgeon s prior experience is evenly

6 EUROPEAN UROLOGY 63 (2013) distributed in all of the comparative subgroups in our study. Similarly, other technical modifications were evenly distributed in all NS grades. Our surgical technique of grade of NS did not change throughout the study period. Conversely, one study suggests that NS is not associated with better continence [44]. The authors viewed potency status as the best indicator of the true extent of NVB preservation and suggested that NVBs should not be preserved in men with baseline sexual dysfunction with an expectation of improving continence. These authors observed results after 24 mo and did not address early continence. Our study shows that NS plays a significant role in the early return of urinary continence. We also did a subgroup analysis in patients with baseline sexual dysfunction and found that lower grade of NS was still associated with better return of early continence (data not shown). In a prior publication, we reported that riskstratified grade of NS technique also affects sexual function recovery [13]. We believe that continence and sexual function are both dependent on the extent of NS. Other studies have shown that men with higher BMI have lower HRQoL scores in most domains [22]; however, no similar effect of BMI was found on early return of urinary continence in our study. In addition, another study found that Charlson comorbidity index and patient age at surgery were independent predictors of the return of urinary continence [21]. Our study did not have patient comorbidity data available and thus we are unable to assess its impact; this is a limitation of the study. Strengths of the present study are that it is one of the largest single-institution and single-surgeon series investigating urinary continence after RALP and it presents a novel approach to NS RALP. However, our study is not without limitations. The extensive experience of the surgeon may have influenced the continence outcomes of the present study, and thus the results cannot be generalized. In addition, continence outcomes were based on one question, the study was not randomized, and there was no control group. The grading of NS is a subjective measure and is not standardized. There is also a possibility of selection bias because potentially younger and more potent patients were selected for a better NS procedure. 5. Conclusions Our study reports a correlation between risk-stratified grade of NS technique and early return of urinary continence, as patients with lower grade (higher degree) of NS achieved an early return of urinary continence without compromising oncologic safety. Author contributions: Ashutosh Tewari 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. Study concept and design: Srivastava, Tewari. Acquisition of data: Durand, Gruschow, Peyser, Chughti, Harneja. Analysis and interpretation of data: Srivastava, Chopra, Lee, Sooriakumaran, Durand, Herman, Chughti, Leung, Lee, Pham, Robinson, Shevchuk, Tewari. Drafting of the manuscript: Srivastava, Chopra, Lee, Sooriakumaran, Herman, Chughti, Leung, Lee, Pham, Robinson, Shevchuk, Tewari. Critical revision of the manuscript for important intellectual content: Srivastava, Chopra, Lee, Sooriakumaran, Herman, Chughti, Durand, Leung, Lee, Pham, Robinson, Shevchuk, Tewari. Statistical analysis: Srivastava, Chopra. Obtaining funding: None. Administrative, technical, or material support: Leung, Tewari. Supervision: Tewari. Other (specify): None. Financial disclosures: Ashutosh Tewari 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: Dr. Ashutosh Tewari is the principal investigator on research grants from Intuitive Surgical, Inc. (Sunnyvale, CA, USA), the Prostate Cancer Foundation, and the National Institute of Bioimaging and Bioengineering (RO1EB ); he is also the endowed Ronald P. Lynch Professor of Urologic Oncology and director of the LeFrak Institute of Robotic Surgery, Weill Cornell Medical College. Funding/Support and role of the sponsor: None. References [1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61: [2] Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128: [3] Tewari AK, Srivastava A, Menon M. A prospective comparison of radical retropubic and robot-assisted prostatectomy: experience in one institution. BJU Int 2003;92: [4] Tewari A, Sooriakumaran P, Bloch DA, Seshadri-Kreaden U, Herbert AE, Wiklund P. Positive surgical margin and perioperative complication rates of primary surgical treatments for prostate cancer: a systematic review and meta-analysis comparing retropubic, laparoscopic, and robotic prostatectomy. Eur Urol 2012;62:1 15. [5] Trinh QD, Sammon J, Sun M, et al. Perioperative outcomes of robotassisted radical prostatectomy compared with open radical prostatectomy: results from the nationwide inpatient sample. Eur Urol 2012;61: [6] Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 2008;358: [7] Eastham JA, Kattan MW, Rogers E, et al. Risk factors for urinary incontinence after radical prostatectomy. J Urol 1996;156: [8] Nandipati KC, Raina R, Agarwal A, Zippe CD. Nerve-sparing surgery significantly affects long-term continence after radical prostatectomy. Urology 2007;70: [9] Burkhard FC, Kessler TM, Fleischmann A, Thalmann GN, Schumacher M, Studer UE. Nerve sparing open radical retropubic prostatectomy does it have an impact on urinary continence? J Urol 2006;176: [10] Choi WW, Freire MP, Soukup JR, et al. Nerve-sparing technique and urinary control after robot-assisted laparoscopic prostatectomy. World J Urol 2011;29:21 7. [11] Mottrie A, Gallina A, De Wil P, Thuer D, Novara G, Ficarra V. Balancing continence function and oncological outcomes during robot-assisted radical prostatectomy (RARP). BJU Int 2011;108: [12] Wei JT, Dunn RL, Marovich R, Montie JE, Sanda MG. Prospective assessment of patient reported urinary continence after radical prostatectomy. J Urol 2000;164:744 8.

7 444 EUROPEAN UROLOGY 63 (2013) [13] Tewari AK, Srivastava A, Huang MW, et al. Anatomical grades of nerve sparing: a risk-stratified approach to neural-hammock sparing during robot-assisted radical prostatectomy (RARP). BJU Int 2011;108: [14] Tewari AK, Patel ND, Leung RA, et al. Visual cues as a surrogate for tactile feedback during robotic-assisted laparoscopic prostatectomy: posterolateral margin rates in 1340 consecutive patients. BJU Int 2010;106: [15] Dev H, Rickman D, Sooriakumaran P, et al. Biobanking after roboticassisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies. J Transl Med 2011;9:121. [16] Martinez-Salamanca JI, Rao S, Ramanthan R, et al. Nerve advancement with end-to-end reconstruction after partial neurovascular bundle resection:a feasibility study. J Endourol 2007;21: [17] Gandaglia G, Suardi N, Gallina A, et al. Preoperative erectile function represents a significant predictor of postoperative urinary continence recovery in patients treated with bilateral nerve sparing radical prostatectomy. J Urol 2012;187: [18] Takenaka A, Soga H, Kurahashi T, Miyake H, Tanaka K, Fujisawa M. Early recovery of urinary continence after laparoscopic versus retropubic radical prostatectomy: evaluation of preoperative erectile function and nerve-sparing procedure as predictors. Int Urol Nephrol 2009;41: [19] Sacco E, Prayer-Galetti T, Pinto F, et al. Urinary incontinence after radical prostatectomy: incidence by definition, risk factors and temporal trend in a large series with a long-term follow-up. BJU Int 2006;97: [20] Kundu SD, Roehl KA, Eggener SE, Antenor JA, Han M, Catalona WJ. Potency, continence and complications in 3,477 consecutive radical retropubic prostatectomies. J Urol 2004;172: [21] Novara G, Ficarra V, D Elia C, et al. Evaluating urinary continence and preoperative predictors of urinary continence after robot assisted laparoscopic radical prostatectomy. J Urol 2010;184: [22] Anast JW, Sadetsky N, Pasta D, et al. The impact of obesity on health related quality of life before and after radical prostatectomy (data from CaPSURE). J Urol 2005;173: [23] Tewari A, Peabody JO, FIscher M, et al. An operative and anatomic study to help in nerve sparing during laparoscopic and robotic radical prostatectomy. Eur Urol 2003;43: [24] Srivastava A, Grover S, Sooriakumaran P, Tan G, Takenaka A, Tewari AK. Neuroanatomic basis for traction-free preservation of the neural hammock during athermal robotic radical prostatectomy. Curr Opin Urol 2011;21: [25] Kiyoshima K, Yokomizo A, Yoshida T, et al. Anatomical features of periprostatic tissue and its surroundings: a histological analysis of 79 radical retropubic prostatectomy specimens. Jpn J Clin Oncol 2004;34: [26] Costello AJ, Brooks M, Cole OJ. Anatomical studies of the neurovascular bundle and cavernosal nerves. BJU Int 2004;94: [27] Costello AJ, Dowdle BW, Namdarian B, Pedersen J, Murphy DG. Immunohistochemical study of the cavernous nerves in the periprostatic region. BJU Int 2011;107: [28] Sievert KD, Hennenlotter J, Laible IA, Amend B, Nagele U, Stenzl A. The commonly performed nerve sparing total prostatectomy does not acknowledge the actual nerve courses. J Urol 2009;181: [29] Eichelberg C, Erbersdobler A, Michl U, et al. Nerve distribution along the prostatic capsule. Eur Urol 2007;51: [30] Savera AT, Kaul S, Badani K, Stark AT, Shah NL, Menon M. Robotic radical prostatectomy with the veil of Aphrodite technique: histologic evidence of enhanced nerve sparing. Eur Urol 2006; 49: [31] Alsaid B, Bessede T, Diallo D, et al. Division of autonomic nerves within the neurovascular bundles distally into corpora cavernosa and corpus spongiosum components: immunohistochemical confirmation with three-dimensional reconstruction. Eur Urol 2011; 59: [32] Nelson CP, Montie JE, McGuire EJ, Wedemeyer G, Wei JT. Intraoperative nerve stimulation with measurement of urethral sphincter pressure changes during radical retropubic prostatectomy: a feasibility study. J Urol 2003;169: [33] Ko YH, Coelho RJ, Chauhan S, et al. Factors affecting return of continence 3 months after robot-assisted radical prostatectomy: analysis from a large, prospective data by a single surgeon. J Urol 2012;187: [34] Kessler TM, Burkhard FC, Perimenis P, et al. Attempted nerve sparing surgery and age have a significant effect on urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution. J Urol 2004;172: [35] Abel EJ, Masteron TA, Warner JN, Valentine K, Dechet C. Nervesparing prostatectomy and urinary function: a prospective analysis using validated quality-of-life measures. Urology 2009;73: [36] Tseng TY, Kuebler HR, Cancel QV, et al. Prospective health-related quality-of-life assessment in an initial cohort of patients undergoing robotic radical prostatectomy. Urology 2006;68: [37] Kessler TM, Burkhard FC, Studer UE. Nerve-sparing open radical retropubic prostatectomy. Eur Urol 2007;51:90 7. [38] Greco F, Hoda MR, Wagner S, et al. Bilateral vs unilateral laparoscopic intrafascial nerve-sparing radical prostatectomy: evaluation of surgical and functional outcomes in 457 patients. BJU Int 2011;108: [39] Namiki S, Saito S, Nakagawa H, Sanada T, Yamada A, Arai Y. Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study. J Urol 2007;178: [40] Kubler HR, Tsent TY, Sun L, Vieweg J, Harris MJ, Dahm P. Impact of nerve sparing technique on patient self-assessed outcomes after radical perineal prostatectomy. J Urol 2007;178: [41] Takenaka A, Soga H, Sakai I, et al. Influence of nerve-sparing procedure on early recovery of urinary continence after laparoscopic radical prostatectomy. J Endourol 2009;23: [42] Kalble T, Schmitt C, Bartschat T, Alt B, Yiakoumos T. Descending nerve-sparing radical prostatectomy results and consequences. Aktuelle Urol 2010;41(Suppl 1):S66 9. [43] Vickers AJ, Cronin AM, Masterson TA, Eastham JA. How do you tell whether a change in surgical technique leads to a change in outcome? J Urol 2010;183: [44] Marien TP, Lepor H. Does a nerve-sparing technique or potency affect continence after open radical retropubic prostatectomy? BJU Int 2008;102: