Cutting-Edge Urology Department: Robotic Surgery & Quality of Life

1. Ente Ecclesiastico Ospedale Generale Regionale “F. Miulli” Acquaviva delle Fonti Struttura Complessa di Urologia Centro di Chirurgia Robotica - Laparoscopica – Mininvasiva Direttore: Giuseppe Mario Ludovico UROLOGY miUlli DEPARTMENT CHIRURGIA ROBOTICA E QUALITA’ DI VITA Giuseppe Mario Ludovico Martina Franca 15 dicembre 2012

2. UROLOGY miUlli DEPARTMENT The most updates European Association of Urology (EAU) guidelines report about: bilateral nerve-sparing radical retropubic prostatectomy (BNSRP) unilateral nerve-sparing radical retropubic prostatectomy (UNSRP) represent the recommended approach of choise in all men with both a normal preoperative erective-function (EF) and organ confined disease Heidenreich A., Bellmunt J, et all; EAU GUIDELINES; 2011

3. Since the introduction of Patrick Walsh’s tecnique, open radical prostatectomy (RP) is the standard surgical treatment of localised Pca. Walsh PC: J Urol 2000 ...WHICH ARE THE OUTCOMES AFTER RADICAL PROSTATECTOMY FOR A LOCALIZED PROSTATE CANCER ? UROLOGY miUlli DEPARTMENT

4. UROLOGY miUlli DEPARTMENT The current robotic literature reveals 12-months potency outcomes favorable (70 to 80%) with the robotic approach and comparable to even longer term (24 months) data of expert open series (46% to 54%). Berryhill R. Jr, Jhaveri J et al: Urology 2008 Ficarra V., Novara G. et al: Eur Urol. 2012 Box GN Ahlering TE: Curr. Opin. Urol 2006 3-month potency outcomes (46% to 54%) seem to suggest the relatively rapid return of erectile function, Box GN Ahlering TE: Curr. Opin. Urol 2009

5. UROLOGY miUlli DEPARTMENT Comprehensivereviewincluding RRP seriespubblishedbetween 1990 and 2005 showed a wide rangeofrecoveryoferectilefunctionafter a minimunfollow up of 12 mo., in patientswhoreceivedbilateral NSRRP showingpotencyratesrangingfrom 31% to 86%. Dubbelman YD, Dohle GR, etall: Eur Urol 2006 Comprehensivereviewincluding RRP seriespubblishedbefore 2005 showedthat the prevalenceoferectiledysfunctionaccordingtodifferencedefinitionwas 47,8% after RRP and 24,2% after RARP. The cumulative analysisshowed a statisticallysignificantadvantage in favourof RARP ( OR :2,84; 95% CI: 1.48-5,43; p= 0,002). Ficarra V, Novara G et al: BJU Int, 2009 Di Pierro GB, Baumeister P et al: Eir. Urol., 2011 Kim Sc, Song C: Eur urol., 2011 Rocco B., Matei DV et al: BJU Int, 2009

6. UROLOGY miUlli DEPARTMENT How we’ll perform a TRUE NERVE SPARING PROCEDURE? or ..Where are really the NVBs? The real problem isn’t this: If the open radical prostatectomy is better than robotic radical prostatectomy, we’ll obtain or not nerve preservation but this one:

7. UROLOGY miUlli DEPARTMENT New anatomicconcepts distribution and courseof the cavernousnerves, New anatomictecniques anteriorincisionof the periprostatic fascia inter- or intrafascialsurgicalplanes New devices thermal or athermaldissectionof the neurovascularbundles i.e. monopolar vs bipolar vs clips, colddissection, countertraction Surgeon’s experience case-load, high volume centre, learning curve Costs

8. UROLOGY miUlli New «anatomic concepts» DEPARTMENT Initially, Walsh’s description of the anatomic nerve-sparing tecnique in 1982 was based on the concept that the neurovascular bundles (NVBs) are situated posterolaterally and simmetrically to the prostate in the space among the levator fascia, prostatic fascia and Denonvillier’s fascia. Walsh PC, Donker PJ et all.:J. Urol. ,1982 In the last decade, deeper insight into the the distribution and course of the cavernous nerves showed that, especially in men with a small prostate, NVBs may have either an anterolateral position or, rarely, an asymmetric posterolateral position on one side while lateral on the other. Menon M., Tewari A. et al: J Urol 2003 Kiyoshima K. Yokomizo A. et al: Jpn J Clin Oncol, 2004 Tewari A, Rao S. et al: BJU Int, 2008

9. UROLOGY miUlli New «anatomic concepts» DEPARTMENT These new anatomic concepts supported the incision of the periprostatic fascia anteriorly and parallel to the NVBs preserves cavernous nerve located at both the posterolateral and anterolateral surfaces of the prostate. Menon M., Tewari A. et al: J Urol 2003 The multiple compartments that could be developed from the levator fascia to the prostate capsula by entering fascial planes during surgery explain the possibility of realizing a different extension of the nerve-sparing procedure according to cancer risk stratification and patient preoperative characteristics Tewari A., Rao S. et al: BJU Int, 2008

10. UROLOGY miUlli New «anatomic concepts» DEPARTMENT Graefen et al and Montorsi et al demonstred the feasibility of the anterior incision of the periprostatic fascia and the possibility of realizing an interfascial or intrafascial surgical plane in open surgery. Graefen M. Walz J. et al: Eur Urol, 2006 Montorsi F., Salonia A. et al: Eur Urol, 2005 The influence of anterior periprostatic nerve tissue suggests the use of a more anterior incision of the fascia, as Briganti experience Briganti A.,Salonia A. et al.: EAU-EBU Update, 2006 In order to spare these anterior fibres, the surgeon should choose a more ventral incision in the mid-part as suggested similarly by Montorsi et al. with an even higher incision at the 11-1 o'clock position Montorsi F. Salonia A. et al.:Eur Urol., 2005

11. UROLOGY miUlli DEPARTMENT But what is the exact distribution of periprostatic autonomic nerves ?

12. UROLOGY New «anatomic concepts» miUlli DEPARTMENT The largest percentage of periprostatic nerves is located in the dorsolateral position Periprostatic nerve distribution is variable, with a high percentage of nerves in the ventrolateral and dorsal positon in some cases The periprostatic nerve density decreaseto the base towards the apex A significant portion of nerves of the NVB appearsto branchinto the prostate Thehighest densityof capsular nerves is found at the apex Ganzer R., Blana A., et coll: Eur. Urol, 2008

13. UROLOGY miUlli New «anatomic concepts» DEPARTMENT Therefore, it is recommended that the surgeon focus on nerve preservation in particular at the apex, starting in the anterior at the mid section as well as the common posterolateral course Sievert KD., Hennenlotter J. et al.: Eur Urol., 2010 ...the neurovascular bundle appears to be a complex confluence of nerves passing through the posterolateral main track in different inclined courses without forming a distinct bundle of parallel nerves

14. UROLOGY miUlli New «anatomic concepts» DEPARTMENT The role of accessory pudendal artery (APAs) in normal erectile function, and their impact on postoperative potency and eventually on continence has become a topic of increasing interest. Some studies have shown that, when present,APAs may often represent the only arterial supply to the penis Myers RP.: Urol. Clin North Am., 2001 Breza J., Abeserif SR. Et al .: J.Urol., 1989

15. UROLOGY miUlli New «anatomic concepts» DEPARTMENT Iacono e Giannella demonstrated that progressive fibrosis in the corpora cavernosa after RP results from denervation and/or an ischemic process, which is caused in turn by the ligation of anomalous pudendal artery branches or of venous plexuses that drain to or from the corpora cavernosa. Fibrosis and the subsequent loss in elasticity and function of erectile tissue probably togheter cause erectile dysfunction Iacono F., Giannella R. et coll.: J of Urol 2005

16. UROLOGY miUlli New «anatomic concepts» DEPARTMENT The Mayo clinic group emphasized in open bilateral neurovascular bundle preservation (BNVBP) during RRP the potential role of: • HAR, i.e high anterior release of the levator fascia and NVBs • surgical loupe magnification (x 4,3) Hubanks JM, Myers RP et al: Eur Urol, 2012

17. UROLOGY miUlli New «anatomic concepts» DEPARTMENT «When you perform an intrafascial nerve -sparing approach or “veil of aphrodite” tecnique,you make a high lateral incision of the periprostatic fascia in order to preserve the nerve tissuewithin the periprostatic fascia in the lateral and ventrolateral position » Ganzer R., Blana A., et coll: Eur. Urol, 2008

18. UROLOGY miUlli New «anatomic concepts» DEPARTMENT Shikanov et al analyzed the impact of the extension of the nerve-sparing procedure, comparing pts that received intrafascial nerve sparing versus extrafascial nerve preservation observing a significant advantages in term of mean potency rate at 3,6 and 12 in favour of intrafascial nerve sparing procedures Shikanov S., Woo J et al: Urology 2009

19. UROLOGY miUlli DEPARTMENT New «anatomic concepts» H. Huland et Al: Eur Urol 2011

20. DETRUSOR APRON UROLOGY miUlli DEPARTMENT The Myers detrusor apron is an extension of the anterior longitudinal smooth muscle of the bladder (detrusor) in front of the anterior commissure (isthmus) of the prostate.It is a conglomerate of groups longitudinal smooth muscle and veins.Its thickness is greater in the midline of the bladder neck. Laterally, it blends with the arch of the pelvic fascia tendon.Represents a direct continuity of the front wall of the bladder with pubis, through the puboprostatic ligaments

21. UROLOGY miUlli DEPARTMENT Pubo prostatic ligaments Detrusor apron Pelvic floor CONTINENCE ERECTION Myers, Menon, Walz, Montorsi, Rocco et Al Eur Urol 2010

22. UROLOGY APEX DISSECTION miUlli DEPARTMENT Urethral functional lenght 1,5 – 2,4 cm Intra apex localization near colliculus Omega shape Outer layer of striated muscle Inner layer of smooth muscle Surrounding structures do not allow for anatomic urethral dissection H. Huland et Al: Eur Urol 2011

23. UROLOGY APEX DISSECTION miUlli DEPARTMENT When the prostate apex covers the urethral muscles Shortening functional urethra Incontinence SE Lee et Al. Urology 2006 H. Huland et Al: Eur Urol 2011

24. UROLOGY APEX DISSECTION miUlli DEPARTMENT ANTERIOR WALLcovered by the DVC and striated muscle detrusor apron DORSO LATERAL WALL made from the apex and neurovascular tissue POSTERIOR WALL related to medial dorsal raphe SE Lee et Al. Urology 2006 H. Huland et Al: Eur Urol 2011

25. UROLOGY miUlli APEX DISSECTION DEPARTMENT ventral dissection of urethral sphincter V shaped SE Lee et Al. Urology 2006 H. Huland et Al: Eur Urol 2011

26. UROLOGY APEX DISSECTION miUlli DEPARTMENT Posterior urethra incised cranially colliculus Ventral sutures past supported with the segment of detrusor apron SE Lee et Al. Urology 2006 H. Huland et Al: Eur Urol 2011

27. UROLOGY miUlli DEPARTMENT Anatomic working angles ? RRP LRP RALP

28. UROLOGY miUlli INTERFASCIAL SURGICAL PLANE DEPARTMENT

29. UROLOGY INTRAFASCIAL SURGICAL PLANE miUlli DEPARTMENT

30. UROLOGY miUlli NERVE SPARING DEPARTMENT

31. UROLOGY miUlli ACCESSORY PUDENDAL ARTERY DEPARTMENT

32. UROLOGY APEX miUlli DEPARTMENT

33. UROLOGY ANASTOMOSIS miUlli DEPARTMENT

34. Some studies evaluated the difference between thermal and athermal dissection of the neurovascular bundles: Ahlering et al compared pts receiving cautery nerve sparing versus cautery-free cavernous nerve preservation patients observing a significant advantages in favor of athermal dissection 24 mo. after the procedures. Ahlering TE, Rodriguez E et al: J. Endourol, 2008 Samadi et al compared patients who received an anterograde cautery nerve- sparing procedure using the bipolar device with two other groups who underwent atherml dissection using clips and a «curtain» tecnique observing that mean potency rate at 3,6 and 12 were 44%, 50% and 66%, respectively. Samadi DB, Munter P.et al: J Endourol, 2010 UROLOGY New devices miUlli DEPARTMENT

35. UROLOGY New devices miUlli DEPARTMENT Finley et al. evaluated the potential role of cold dissection of the cavernous nerves ( plus an endorectal cooling balloon cycled with 4 C°) observing a statistically significant better 12-mo potency rates Finley DS, Osann K.: J Endourol, 2009 Kowalczyk et al reported weak statistical significant advantages in favor of patients receveing a nerve sparing tecnique without cauterysation 5 mo after RARP. Kowalczyk KJ; Huang Acet al: Eur Urol, 2011 This study confirmed two aspects related to the nerve sparing procedure : • the effect of mechanical trauma on the function of the cavernous nerves during the early follow-up • The short time of this negative effect during the robotic procedure

36. Surgeon’s experience UROLOGY miUlli DEPARTMENT A common refrain from busy robotic surgeons, residents and community urologists is that RALP IS EASY TO LEARN COMPARED TO LRP OR EVEN RRP. Certainly, the laparoscopic surgeon may require only 12 to 20 cases to develop comfort with the platform and the steps of the procedure J.A. Cadeddu: J. Urol., 2010 However, is this the real learning curve? Herrel et al reported that results comparable to RRP were not attained until 150 cases and that “self-perception” of a comparable degree of comfort with RALP and RRP was not recognized until greater than 250 RALP procedures. Herrel SD, Smith JA Jrs: Urology, 2005

37. UROLOGY miUlli DEPARTMENT MIULLI ROBOTIC CENTER RALP Volume Feb 2006 – Dec 2008 serie pioneristica 136 3 bracci April 2009 – Sep 2012 serie matura 633 4 bracci

38. UROLOGY APR 2009 – JUL 2012 600 PAZIENTI RALP miUlli DEPARTMENT Follow-up medio 18 mesi (3 – 39)

39. UROLOGY Dati Intervento miUlli DEPARTMENT

40. UROLOGY miUlli Outcomes patologici DEPARTMENT

41. UROLOGY miUlli Outcomes patologici DEPARTMENT

42. Nerve Sparing Scoring System UROLOGY miUlli Perfect nerve sparing Minor damage Moderate damage Complete resection DEPARTMENT GLOBAL NSSS ≤ 4 Nelson J Urol 2009

43. UROLOGY miUlli Erection Hardness Score DEPARTMENT 0 Penis not enlarge 1 Penis is larger but not hard 2 Penis is hard but non enough for penetration 3 Penis is hard enough for penetration but not completely hard 4 Penis is completely hard and fully rigid REF ≥ 3 Mulhall J Sex Med 2007

44. Outcomes funzionali UROLOGY miUlli DEPARTMENT Protocollo riabilitativo PDE5-I Erection Hardness Score 0 Penis not enlarge 1 Penis is larger but not hard 2 Penis is hard but non enough for penetration 3 Penis is hard enough for penetration but not completely hard 4 Penis is completely hard and fully rigid REF ≥ 3 Mulhall MD 2007

45. UROLOGY miUlli Outcomes funzionali DEPARTMENT

46. UROLOGY Intrafasciale Bladder neck sparing miUlli DEPARTMENT Outcomes funzionali G.M. Ludovico S.I.U. 2012

47. UROLOGY Tasso globale complicanze miUlli RALP - literature Tasso globale complicanze 1 – 21% High volume 10% DEPARTMENT Miulli Clavien Clavien I 8% Calvien II 5% Clavien III 0,8% Clavien IV 0,15%

48. UROLOGY Tasso globale complicanze miUlli DEPARTMENT Conversione open nessuna 0 Sanguinamento 16 2,6% Cateterismo prolungato 8 1,3 no V-lock Deiscenza anastomosi nessuna 0 Stenosi Anastomosi 4 0,7% no V-lock Embolia 1 0,15% Lesione retto 1 0,15 Ematoma parete 4 0,7% Linfocele 25 4,16% Exitus nessuno 0 Follow-up breve Post dimissione Analisi prognostica relativa al rischio che si verificassero

49. UROLOGY miUlli CONCLUSIONS DEPARTMENT Surgeon experience Surgical institutional volume Anatomic working angles Robotic team Better outcomes

50. UROLOGY miUlli CONCLUSIONS DEPARTMENT RALP is displacing RRP as the gold standard surgical approach for clinically localised prostate cancer in the United States and is also being increasingly used in Europe and other parts of the world. This trend has occurred despite the paucity of high-quality evidence to support its relative superiority to more-established treatment modalities. Recent in-depth systematic reviews of the literature have compared the results of RRP versus LRP/RALP. Systematic review indicates that RALP is advantageous in preservation of continence and potency recovery Ficarra V, Eur Urol 2012. Coelho RF;J Endourol 2010. Kang DC, Eur Urol 2010.