1. Predicting toxicity after surgery: erectile dysfunction Francesco Montorsi Andrea Gallina Vita-Salute San Raffaele University URI - Urological Research Institure Milan, Italy

2. Mulhall J. J Urol, 181:462-471, 2009 20-90% Fowler FJ Jr, et al. Urology, 42:622, 1993 Kundu SD, et al. J Urol, 172:2227, 2004 Litwin MS, et al. Urology, 54:503, 1999 Rabbani F, et al. J Urol, 164:1929, 2000 Rozet F, et al. J Urol, 174:908, 2005 Stanford JL, et al. JAMA, 283:354, 2000 Walsh PC, et al. Urology, 55:58, 2000

3. Burnett AL, et al. J Urol, 178:597-601, 2007

7. FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY: 1. PRE-OPERATIVE FACTORS 3. POST-OPERATIVE FACTORS 2. INTRA-OPERATIVE FACTORS a. Extent of NVBV preservation b. Surgical experience c. Surgical technique a. Adequate on demand or rehabilitative treatment a. Pre-operative erectile function b. Patient age c. Age difference between patient and partners d. Comorbidity profile

8. Rabbani et al J Urol ,164:1929-34,2000 >65 vs <60 yrs p=0.0007 PRE-OPERATIVE FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY Age at surgery

9. ERECTILE FUNCTION OUTCOME OF UNTREATED PATIENTS AFTER BILATERAL NERVE SPARING RADICAL PROSTATECTOMY p<0.001 Gallina A, et al. 2011 submitted EF recovery according to age at surgery <55 60.0-64.9 55.0-55.9 65.0-69.9 >70

10. Rabbani et al J Urol ,164:1929-34,2000 PRE-OPERATIVE FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY Partial vs Full p=0.038 Pre-operative erectile function

11. ERECTILE FUNCTION OUTCOME OF UNTREATED PATIENTS AFTER BILATERAL NERVE SPARING RADICAL PROSTATECTOMY >26 22-25 18-21 11-17 1-10 p<0.001 Gallina A, et al. 2011 submitted EF recovery according to pre-operatory IIEF-EF

12. Charlson Comorbity Index p=0.03 ERECTILE FUNCTION OUTCOME OF UNTREATED PATIENTS AFTER BILATERAL NERVE SPARING RADICAL PROSTATECTOMY Gallina A, et al. 2011 submitted 0 2+ 1

13. AGE DIFFERENCE BETWEEN PATIENT AND PARTNER IS A PREDICTIVE FACTOR OF POTENCY RATE FOLLOWING RADICAL PROSTATECTOMY Descazeaud et al, J Urol 2006;176:2594-8 Age difference was an independent predictive factor of overall potency status following RP (p=0.008) 200 consecutive patients treated with RP with a minimum 1-year follow-up ^ Potency was defined as erection sufficient for sexual intercourse with vaginal penetration

15. FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY: 1. PRE-OPERATIVE FACTORS 3. POST-OPERATIVE FACTORS 2. INTRA-OPERATIVE FACTORS a. Extent of NVBV preservation b. Surgical experience c. Surgical technique a. Adequate on demand or rehabilitative treatment a. Pre-operative erectile function b. Patient age c. Age difference between patien and partners d. Comorbidity profile

16. Changes in IIEF-5 score after nerve sparing radical prostatectomy showing significant decrease in IIEF-5 score depending on extent of nerve sparing PREDICTION OF POSTOPERATIVE SEXUAL FUNCTION AFTER NERVE SPARING RADICAL RETROPUBIC PROSTATECTOMY Michl et al. J Urol 2005,176,227-31 INTRA-OP FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY

17. Ayyathurai et al, BJU Int. 2008;101:833-6. FACTORS AFFECTING ERECTILE FUNCTION AFTER RADICAL RETROPUBIC PROSTATECTOMY: RESULTS FROM 1620 CONSECUTIVE PATIENTS UNI AND MULTIVARIABLE ANALYSES PREDICTING EF RECOVERY AFTER SURGERY The proportion of men with a return of EF (erectile function sufficient for intercourse) was directly proportional to the number of previous RRPs performed by the surgeon: 60% of men reported a returned of potency from the first 265 RRPs, compared to 75% from the most recent 265 ( p =0.001).

18. INTRAFASCIAL NERVE SPARING RADICAL PROSTATECTOMY Eichelberg C et al . Eur Urol. 2007;51:105-10 Montorsi F et al Eur Urol 2005;48:938–45 Masterson TA, et al. BJU Int. 2008; 101 : 1217-22 . Nielsen ME, et al J Urol. 2008 180:2557-64 MSKCC series: 6-month EF recovery rates 67% vs 45%, respectively (p=0.01)

19. RALP VS OPEN RADICAL PROSTATECTOMY: RETROSPECTIVE COMPARISON OF A SINGLE CENTER Log rank p<0.001 RALP (n=289) 533 patients treated with bilateral intra-fascial nerve sparing radical prostatectomy RRP (n=244) Buffi N et al, Eur Urol Suppl 2010;58, abstract#81

20. Low risk of ED (age ≤ 65 years, IIEF-EF ≥ 26, CCI ≤ 1) p < 0.001 RALP VS OPEN RADICAL PROSTATECTOMY: RETROSPECTIVE COMPARISON OF A SINGLE CENTER Intermediate risk of ED (age 66-69 years or IIEF-EF 11-25,CCI ≤1) RALP RRP p < 0.001 High risk of ED (age ≥70 years or IIEF-EF ≤10 or CCI ≥2) RALP RRP p = 0.3 RALP RRP

21. COMPARISON OF OPEN AND ROBOTIC-ASSISTED LAPAROSCOPIC RADICAL PROSTATECOMY WITH A BILATERAL INTRAFASCIAL NERVE-SPARING APPROACH: RESULTS OF A HIGH VOLUME SINGLE SURGEON SERIES. Gallina et al. 2011, submitted KM curves predicting EF recovery according to surgical approach 6 months 12 months 24 months Open IBNS 28% 42% 51% RALP-IBNS 61% 69% 69%

22. COMPARISON OF OPEN AND ROBOTIC-ASSISTED LAPAROSCOPIC RADICAL PROSTATECOMY WITH A BILATERAL INTRAFASCIAL NERVE-SPARING APPROACH: RESULTS OF A HIGH VOLUME SINGLE SURGEON SERIES. Gallina et al. 2011, submitted Only preop fully potent patients (IIEF-EF ≥ 26) , aged <65 years 6 months 12 months 24 months Open IBNS 38% 57% 68% RALP-IBNS 71% 81% 81%

23. FACTORS PREDICTING RECOVERY OF ERECTIONS AFTER RADICAL PROSTATECTOMY: 1. PRE-OPERATIVE FACTORS 3. POST-OPERATIVE FACTORS 2. INTRA-OPERATIVE FACTORS a. Extent of NVBV preservation b. Surgical experience c. Surgical technique a. Adequate on demand or rehabilitative treatment a. Pre-operative erectile function b. Patient age c. Age difference between patient and partner d. Comorbidity profile

25. RECOVERY OF SPONTANEOUS ERECTILE FUNCTION AFTER NSRRP WITH AND WITHOUT EARLY INTRACAVERNOUS INJECTIONS OF ALPROSTADIL: RESULTS OF A PROSPECTIVE, RANDOMIZED TRIAL. Complications in patients treated with alprostadil injections: 3 cases (19%) Montorsi F et al. J Urol.158:1408-10,1997 Group 2 Group 1 p value Recovery of spontaneous erection sufficient for satisfactory sexual intercourse 8 (67%) 3 (20%) <0.001

28. Effects of nightly sildenafil treatment on recovery of spontaneous erections: results *Responders: patients with combined IIEF Q3/4 score of ≥ 8 and positive response to question: “ Over the past 4 weeks, have your erections been good enough for satisfactory sexual activity? ” at 8 weeks after discontinuation of drug Nightly sildenafil (50 – 100 mg) vs placebo after 36 weeks of treatment in 123 patients with normal preoperative EF, wishing to return to sexual activity Placebo n=25 Sildenafil n=51 † p=0.0156 Responders %* † Padma-Nathan et al. Int J Impot Res;20:479-86,2008

29. REINVENT: IIEF-EF domain score ≥22 after 2 months of open-label on-demand vardenafil treatment n=138 n=142 n=146 Patients previously on: Patients with IIEF-EF score ≥22 (%) Montorsi et al. Eur Urol. 2008;54:924-31 Placebo Vardenafil nightly Vardenafil on-demand

30. KAPLAN-MEIER CURVES PREDICTING EF RECOVERY ACCORDING TO THE TYPE OF TREATMENT IN THE OVERALL POPULATION TREATED WITH BNSRP (N=435) CHRONIC PDE5-I (n=95) ON-DEMAND PDE5-I (n=147) p=0.1 NO TREATMENT (n=193) p<0.001 Briganti A et al, AUA, 2009 % 1 yr % 2 yrs Chronic PDE5-I 62.4 78.5 On demand PDE5-I 48.0 66.9 No treatment 28.1 35.8

31. KAPLAN-MEIER CURVES: EF RECOVERY ACCORDING TO THE TYPE OF TREATMENT IN PTS AT LOW RISK OF ED (age ≤ 65 yrs, IIEF-EF ≥ 26, CCI ≤1 ; N=184) p=0.04 p=0.5 CHRONIC PDE5-I ON-DEMAND PDE5-I NO TREATMENT NO TREATMENT p=0.02 p=0.8 ON-DEMAND PDE5-I CHRONIC PDE5-I KAPLAN-MEIER CURVES : EF RECOVERY ACCORDING TO THE TYPE OF TREATMENT IN PTS AT HIGH RISK OF ED (age ≥ 70 yrs or IIEF-EF ≤ 10 or CCI ≥ 2; N=136) Briganti A et al, AUA, 2009 % 1 yr % 2 yrs Chronic PDE5-I 77.1 87.1 On demand PDE5-I 74.5 89.8 No treatment 67.2 69.5 % 1 yr % 2 yrs CHRONIC PDE5-I 37.4 67.8 ON DEMAND PDE5-I 30.9 63.7 NO TREATMENT 20.2 23.5

32. KAPLAN-MEIER CURVES PREDICTING EF RECOVERY ACCORDING TO THE TYPE OF TREATMENT IN PATIENTS AT INTERMEDIATE RISK OF ED (age 66-69 yrs or IIEF-EF 11-25, CCI≤1 ; N=115) p=0.04 p=0.02 NO TREATMENT CHRONIC PDE5-I ON-DEMAND PDE5-I Briganti A et al, AUA, 2009 % 1 yr % 2 yrs CHRONIC PDE5-I 33.2 74.5 ON DEMAND PDE5-I 28.1 52.9 NO TREATMENT 33.3 39.4

34. Initial challenge with sildenafil citrate (4 attempts with 100 mg) Sildenafil 100 mg 3 times/week Erection sufficiently hard for penetration Trimix (papaverine 30 mg/mL, phentolamine 1 mg/mL and PGE1 10 μg/mL) 3 times/week Mulhall et al. BJU Int 2010; 105:37-41

35. Mulhall et al. BJU Int 2010; 105:37-41 Delaying the start of rehabilitation of EF was associated with poorer outcomes for EF

38. AT LEAST ONE PDE5 INHIBITOR DOSE PER WEEK SHOULD BE TAKEN IN ORDER TO IMPROVE ERECTILE FUNCTION RECOVERY AFTER BILATERAL NERVE SPARING RADICAL PROSTATECTOMY Gallina A et al. AUA meeting 2011 <1 pill per week ≥ 1 pill per week Log rank p<0.001 KM curves predicting EF recovery according to the number pills taken

41. Müller A et al. J Sex Med 2009; 6:2806–12

42. Stepwise logistic regression analysis predicting failure to recover natural erections sufficient for intercourse Müller A et al. J Sex Med 2009; 6:2806–12

44. AVAILABLE TOOLS FOR PREDICTING ERECTILE FUNCTION RECOVERY AFTER RADICAL PROSTATECOTMY

46. Briganti et al. J Sex Med 2010;7:2521–25 Erectile function recovery in the overall population

47. Briganti et al. J Sex Med 2010;7:2521–25 Erectile function recovery according to the novel risk stratification

48. Briganti et al. J Sex Med 2010;7:2521–25 Novel risk stratification according to post-operative treatment No therapy Pro-erectile therapy

49. Briganti et al. J Sex Med 2010;7:2521–25 Multivariable cox regression analyses predicting EF recovery

52. Eastham JA et al J Urol. 179:2207-10, 2008 Probability of attaining and maintaining trifecta in patient after RP

53. AUC:77.3% Eastham JA et al J Urol. 179:2207-10, 2008