Oncological outcomes after robot-assisted radical prostatectomy: long-term follow-up in 4803 patients

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1 Oncological outcomes after robot-assisted radical prostatectomy: long-term follow-up in 4803 patients Shyam Sukumar, Craig G. Rogers, Quoc Dien Trinh, Jesse Sammon, Akshay Sood, Hans Stricker, James O. Peabody, Mani Menon and Mireya Diaz-Insua Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA S.S. and C.G.R. contributed equally Objective To evaluate oncological outcomes in patients undergoing robot-assisted radical prostatectomy (RARP) at a high-volume tertiary centre with focus on biochemical recurrence (BCR); previous studies on oncological outcomes for patients undergoing RARP for prostate cancer are limited to small series. Patients and Methods In all, 5152 consecutive patients underwent RARP from 2001 to 2010; 4803 patients comprised the study cohort after exclusions. BCR was defined as a serum prostate-specific antigen (PSA) level of 0.2 ng/ml with a confirmatory value. BCR-free survival (BCRFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and Cox hazards regression models were generated. Results The mean preoperative PSA level was 6.1 ng/ml, pathological Gleason grade and stage were 7 in 68% and pt3 in 34% of patients. There was BCR in 470 patients (9.8%), 31 patients developed metastatic disease (0.7%) and 13 patients died from prostate cancer (0.3%) during a mean (range) follow-up of 34.6 ( ) months. Actuarial 8-year BCRFS, MFS and CSS were 81%, 98.5% and 99.1%, respectively. In patients with node-positive disease, actuarial 5-year BCRFS, MFS, and CSS were 26%, 82%, and 97%. For organ-confined disease, predictors of BCR included pathology Gleason grade (primary Gleason 5 vs 3, hazard ratio [HR] 5.52, P = 0.018; Gleason 4 vs 3, HR 1.97, P = 0.001), preoperative PSA level (10 20 vs 10 ng/ml, HR 2.38, P = 0.001), and surgical margin status (positive vs negative, HR 3.84, P < 0.001) Conclusions RARP appears to confer effective long-term biochemical control. To our knowledge, this is the largest report of oncological outcomes in a RARP series to date. Keywords prostate cancer, biochemical recurrence, robotics, prostatectomy, laparoscopy Introduction Prostate cancer remains the most common solid organ malignancy in men in the USA and the second leading cause of cancer death [1]. Radical prostatectomy (RP) is effective in the management of localised prostate cancer [2,3]. However, biochemical recurrence (BCR) will occur in over a quarter of all patients within 10 years of RP [4 7], with a mean time from BCR to metastasis and metastasis to death of 8 and 5 years, respectively [8]. As there has been a stage migration of prostate cancer secondary to widespread PSA screening [9 11], BCR rates in contemporary practice are not clear. There has been a remarkable increase in the use of robot-assisted RP (RARP) for the treatment of prostate cancer. In 2001 <0.3% of all RPs were performed with robotic assistance; however, by % of all RPs in the USA were performed robotically [12]. While recent reports [12 14] have shown that RARP may compare favourably with open retropubic RP (ORP) for perioperative outcomes (including perioperative mortality); long-term oncological outcomes, as with any radical cancer surgery, still remains the most critical benchmark while evaluating equivalence. An assumption underlying the use of RARP is that it provides comparable cancer control to ORP. However, there are few large-scale BJU Int 2014; 114: wileyonlinelibrary.com BJU International 2013 BJU International doi: /bju Published by John Wiley & Sons Ltd.

2 Long-term oncological outcomes after RARP studies describing oncological outcomes after RARP [15,16]. The goal of the present study was to evaluate overall oncological outcomes in patients undergoing RARP at a high-volume tertiary care centre with a 10-year experience in RARP. As biochemical relapse and factors predicting this outcome are key concerns in decision making, counselling and risk stratification in randomised studies [17], we examined BCR rates as the primary endpoint in the present study cohort. To our knowledge, this represents the largest RARP series to date with long-term follow-up for BCR. Patients and Methods Data was prospectively collected in 5152 consecutive patients undergoing RARP for clinically localised prostate cancer between September 2001 and December 2010 at a high-volume tertiary care centre and who were followed-up until April After excluding patients who were lacking a recorded postoperative PSA level at 1 month (172 patients), patients receiving neoadjuvant or prior therapy (151), patients with adjuvant treatment (11), and patients with incomplete pathology data (15), a total of 4803 patients remained, constituting the study cohort. All patients had a preoperative PSA level at diagnosis and a minimum of six-core prostate biopsies that were reviewed by a referee pathologist. Covariates evaluated included age, biopsy Gleason grade, tumour volume, clinical stage (American Joint Committee on Cancer 2009 guidelines) and body mass index (BMI). RARP with a pelvic lymph node dissection (PLND) was performed using a standardised technique described by Menon et al. [18 20], with modifications in technique during the study [21]. Patients with low- to intermediate-d Amico risk disease had PLND involving the external iliac and obturator sites, whereas extended PLND was performed for cases with palpable T2b T3 disease, Gleason score 8 10, or a PSA level of >10 ng/ml. Nerve sparing was performed in patients who were potent (Sexual Health Inventory for Men >17) [22]. Pathological Evaluation The Stanford protocol was used to evaluate RP specimens [23]. Pathological variables studied including pathological stage, Gleason grade, prostate weight, presence of LN disease, perineural invasion, angiolymphatic invasion and surgical margins. Extraprostatic extension was defined as invasion of cancer into soft tissue or muscle. A positive surgical margin was defined as extension of cancer to the inked border. All visible and palpable LNs were dissected and submitted for pathological assessment to evaluate for metastasis. Patient Follow-up Follow-up and demographic information was obtained from a prospective electronic database, institutional electronic medical records, hospital billing records, outpatient records, and communication with patients/physicians. All patients were followed prospectively using data from patient visits and via mailed questionnaires. The serum PSA level was typically measured at 6 weeks and quarterly during the first year, semi-annually during the second year, and annually thereafter. The Institutional Review Board of the Henry Ford Hospital approved the study. BCR was defined in accordance with the American Urological Association Localized Prostate Cancer Update Panel report [24]: one PSA value of 0.2 ng/ml with a second PSA value of >0.2 ng/ml. Metastasis was defined as any radiographic evidence of recurrent disease. Statistical Analysis The Kaplan Meier method was used to estimate time-to-event outcomes and the log-rank method was used to compare survival. Cox proportional hazard regression was used to identify prognostic factors, which were employed in a stepwise selection approach. The assumption of proportional hazards was confirmed for each of the input variables. Among the predictors considered were, patient age (coded as 60 or <60 years), BMI and prostate size, preoperative PSA level (coded as <4, 4 10, 10 20, and 20 ng/ml), pathology Gleason grade, final pathological stage, and modifiers such as perineural and angiolymphatic invasion, tumour volume, margin status and nerve-sparing approach. All statistical analyses were performed by a professional statistician (M.D.). All P values are two-sided, and a level of 0.05 was considered statistically significant. Results Baseline clinical and pathological variables for the 4803 patients in the present cohort are shown in Table 1 stratified by LN status. The mean (SD) age of our cohort was 60 (7.3) years and the preoperative serum PSA level was 6.1 (4.6) ng/ml. The mean (range) and median (interquartile range) follow-up for the entire cohort were 34.6 ( ) months and 26.4 ( ) months, respectively. There was pathological Gleason 3+4 disease in 67.5% and pt3a disease in 34.4% of the present study cohort. Surgical margins were positive in 375 (11.2%) patients with pt2 disease and in 787 (50.5%) patients with pt3 pt4 disease. The BCR rate for the entire cohort was 9.8% (470 patients) at a median follow-up of 26.4 months, with some patients followed for >9.5 years (range months). Of the patients with BCR, 31 patients developed metastatic disease and 13 patients died from prostate cancer. All-cause mortality rate was 1.5% (70 patients) during follow-up. Actuarial 8-year (standard error) BCR-free survival (BCRFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) were 81 (1.3)%, 98.5 (0.3)% and 99.1 (0.4)%, respectively. In patients BJU International 2013 BJU International 825

3 Sukumar et al. Table 1 Clinical and pathological features of 4803 patients undergoing RARP between 2001 and Characteristics* N0 N1 Number of patients Mean (SD): Age, years 60.0 (7.3) 60.6 (7.9) PSA level, ng/ml (n = 4694) 6.1 (4.6) 12.3 (14.9) BMI, kg/m 2 (n = 4686) 27.8 (3.9) 28.4 (4.5) Prostate mass, g (n = 4698) 49.4 (20.1) 53.3 (20.0) Tumour volume, % (n = 4674) 15.1 (12.2) 31.2 (20.3) N (%): Biopsy Gleason score: (53.5) 4 (4.0) (29.0) 25 (25.3) (9.2) 24 (24.2) (8.3) 46 (46.5) Clinical stage: T (75.5) 53 (53.5) T2a 645 (13.7) 18 (18.2) T2b 179 (3.8) 13 (13.1) T2c 243 (5.2) 10 (10.1) T3 86 (1.8) 5 (5.1) Perineural invasion (biopsy): Absent 4032 (85.9) 61 (61.6) Present 661 (14.1) 38 (38.4) Nerve sparing**: Partial 2252 (47.9) 53 (53.5) Prostatic fascia sparing (unilateral/bilateral) 1886 (45.7) 9 (9.1) Wide excision 303 (6.4) 37 (37.4) Pathological Gleason score: (33.2) 0 (0) (44.3) 18 (18.2) (13.9) 21 (21.2) (8.6) 60 (60.6) Pathological stage: pt2a pt2c 3146 (66.8) 4 (4) pt3a 1315 (28.0) 40 (40) pt3b pt4 243 (5.2) 55 (56) Margins: T2-positive 375 (11.9) 0 T3/T4-positive 787 (50.5) 43 (43.4) Perineural invasion (pathology) 3536 (75.1) 98 (99) Angiolymphatic invasion (pathology) 159 (3.4) 56 (56) *Continuous variables are expressed as mean (SD); **Partial nerve sparing: preservation of the dominant neurovascular distribution on the posterolateral prostate. Prostatic fascia sparing: alternatively described as veil of Aphrodite, intrafascial, and high anterior release. with LN-positive disease, actuarial 5-year (standard error) BCRFS, MFS, and CSS were 26.3 (7.3)%, 77.7 (11.7)%, and 96.1 (2.7)%, respectively (Fig. 1A,B). Adjusted hazard ratios (HRs) for prediction of BCR in multivariable Cox proportional hazards regression models for patients with pathological organ-confined disease (OCD), non-ocd and N1 disease are shown in Table 2. For OCD, significant predictors of BCR included pathological Gleason grade (primary Gleason 5 vs 3, HR 5.52, P = 0.018; Gleason 4 vs 3, HR 1.97, P = 0.001), preoperative PSA level ( vs 10 ng/ml, HR 2.38, P = 0.001) and surgical margin status (positive vs negative, HR 3.84, P < 0.001). For patients with non-ocd, in addition to preoperative PSA level, pathological Gleason grade and margin status, angiolymphatic invasion was a significant predictor of biochemical failure (positive vs negative, HR: 2.76, P < 0.001). Figure 2A,B show the actuarial BCRFS for OCD and non-ocd stratified by primary pathological Gleason grade and margin status. While both primary Gleason grade and margin status were significant predictors of BCR in OCD, in non-ocd, there was more substantial stratification of the curves and a 10 20% difference between each subgroup in absolute BCRFS at 7 years. Notably, for patients with OCD, the combination of positive margin status and primary Gleason 3 disease had equivalent outcomes as patients with negative margins and primary Gleason 4 or 5. Table 3 shows the stepwise Cox regression model providing HR estimates for the predictors of metastasis and cancer-specific death. Significant predictors of metastasis included advanced pathological primary Gleason grade (4 5 vs 3, HR 5.36, P = 0.002), advanced pathological stage (seminal vesical invasion vs OCD/extraprostatic extension, HR 6.64, P < 0.001), high preoperative PSA level (>20 vs 20 ng/ml, HR 3.18, P = 0.008) and angiolymphatic invasion (positive vs negative, HR 2.61, P = 0.019). Significant predictors of cancer-specific death included advanced pathology primary Gleason grade (4 5 vs 3, HR 17, P = 0.009) and advanced pathological stage (seminal vesical invasion vs OCD/extraprostatic extension, HR 12.79, P < 0.001). Discussion There have been significant changes in the diagnosis and surgical management of prostate cancer, with increased use of PSA screening, a downward migration of prostate cancer stage and grade [25,26], and the broad adoption of minimally invasive surgical approaches. RARP has become the most frequently performed extirpative treatment for localised prostate cancer in the USA [12] and yet there are few large-scale studies including patients with long-term oncological outcomes [15,16]. Badani et al. [15], in the first study of large-scale oncological outcomes after RARP, reported a BCR rate of 7.3% in 2766 patients undergoing RARP at a median follow-up of 22 months. However, no detailed analysis of predictors of BCR was undertaken at that time. Menon et al. [16], reported BCR rates in 1384 patients with a median follow-up of 5 years. In that study, the probability of BCR was 13.6% at 5 years. Although some patients in the present study are included in that previous report, that study included only patients eligible for 5-year follow-up thereby excluding both the substantial majority of our patients and the statistical element of censoring in evaluating time-to-event outcomes like BCR. We now extend our analysis of BCR to present our entire updated experience and additionally address the burden of LN disease with its attendant effect on oncological outcomes. In the present analysis, the long-term BCRFS rate was 81% at 8 years after 826 BJU International 2013 BJU International

4 Long-term oncological outcomes after RARP Fig. 1 (A) Actuarial BCRFS, MFS, and CSS in 4704 RARP patients with LN-negative disease ( ). (B) Actuarial BCRFS, MFS, and CSS in 99 RARP patients with LN disease (N1; ). a Cancer control outcomes among 4,704 N0 patients after RARP Survival Probability year rates (SE) BFS: 81.0% (1.3) MFS: 98.5% (0.3) CSS: 99.1% (0.4) 0.0 BFS CSS MFS + Censored b Follow-up time, months Outcome BFS CSS MFS BFS = biochemical-recurrence free survival, MFS = metastasis-free survival, CSS = prostate-cancer specific survival; SE: standard error Cancer control outcomes among 99 N1 patients after RARP + Censored 0.8 Survival Probability year rates (SE) BFS: 26.3% (7.3) MFS: 77.7% (11.7) CSS: 96.1% (2.7) 0.0 BFS CSS MFS Follow-up time, months Outcome BFS CSS MFS BFS = biochemical-recurrence free survival, MFS = metastasis-free survival, CSS = prostate-cancer specific survival; SE: standard error RARP (Fig. 1A). Other studies of BCR after RARP include Murphy et al. [27], who reported on 400 patients with a BCRFS of 87% at a median follow-up of 22 months, Barocas et al. [28], who reported a 3-year BCRFS rate of 84%, at a median follow-up of 8 months, Suardi et al. [29] who reported 3- and 5-year BCRFS rates of 94% and 86% in 184 patients with a minimum follow-up of 5 years. More recently, Sooriakumaran et al. [30], reported a BCRFS rate of 84.8% at a median follow-up of 6.3 years and Liss et al. [31] reported a BCRFS rate of 84.9% at 5 years. Several studies have also shown reasonable BCR rates for RP using other surgical approaches. Eastham et al. [32], in a study of 1577 patients undergoing ORP, reported a BCR rate of 9% within 5 years. Roehl et al. [33], in a series of 3478 patients treated with ORP between 1983 and 2003 reported 10-year BCRFS, CSS and OS rates of 68%, 97% and 83%, respectively. The Montsouris group [34] reported a 3-year BCRFS rate of 91% in 1000 consecutive patients undergoing laparoscopic RP. Touijer et al. [35] evaluating their 10-year experience with laparoscopic RP in 1564 patients between 1998 and 2007 BJU International 2013 BJU International 827

5 Sukumar et al. Table 2 Multivariable models predicting biochemical recurrence in 4803 patients undergoing RARP between 2001 and 2010, as stratified by pathological stage and LN status. Covariate* OCD Non-OCD N1 No. of events/no. at risk (%) 124/3133 (4.0) 284/1556 (18.3) 58/99 (58.6) HR (95% CI) P Preoperative PSA level, ng/ml: 10 Referent Referent Referent ( ) ( ) ( ) > ( ) Biopsy Gleason: 2.14 ( ) 1.68 ( ) Referent Referent Referent ( ) 1.67 ( ) 1.86 ( ) Pathology primary Gleason: 3 Referent Referent Referent ( ) ( ) 2.52 ( ) ( ) ( ) 2.53 ( ) Margins: negative Referent Referent Referent positive 3.84 ( ) 2.20 ( ) 1.13 ( ) Angiolymphatic invasion: negative Referent Referent Referent positive 1.59 ( ) ( ) 0.92 ( ) Number of positive LNs: 1 Referent ( ) ( ) *Significant predictors are in bold. reported overall 5- and 8-year BCRFS rates of 78% and 71%, respectively (BCR definition: PSA level of 0.1 ng/ml with confirmatory value or initiation of secondary therapy). Putting the results of the present study in context with the previously mentioned studies, oncological outcomes appear to be primarily determined by the biology of the disease and less so by surgical approach. Pathological features predictive of treatment failure in the present study included preoperative PSA level, Gleason score, and margin status with pathological Gleason grade being the strongest predictor. Despite a predominantly high-to-intermediate risk cancer cohort (pathological Gleason grade of 7 in 68% of patients, and pathological stage of pt3 in 34% of patients), the present BCR rate of 9.8% and actuarial 5- and 8-year BCRFS rates of 87% and 81%, respectively are consistent with reports from large ORP series [4 6,32]. The lack of tactile feedback with RARP has been a matter of much debate and concern, especially as there have been no reports on long-term oncological safety. The present study reports long-term oncological outcomes that are in accordance with other RP techniques. The present study represents the largest RARP series to date, including patients with the longest follow-up for RARP. For the first time in an RARP series, we also report long-term (8 years) CSS and MFS. Thus, the present study, along with other ORP series reporting long-term follow-up [36], represent an important step forward in addressing the extremely pertinent issue of long-term oncological outcomes after RP performed in the contemporary PSA era. However, there are several points that deserve special mention. As a high-volume tertiary referral centre, predominantly treating patients with moderate- to high-risk disease, the present results may not be reliably extrapolated to other therapeutic settings. The present study included our learning curve, which could have influenced the results. 828 BJU International 2013 BJU International

6 Long-term oncological outcomes after RARP Fig. 2 (A) Actuarial BCRFS for patients with OCD stratified by primary Gleason grade and margin status. (B) Actuarial BCRFS for patients with non-ocd stratified by primary Gleason grade and margin status. a Biochemical recurrence-free survival for organ confined disease by margin status and Gleason score Survival probability Censored log-rank P < Follow-up time, months Group 1: R0G3 2: R0G4 3: R1G3 4: R1G4 G3 = primary Gleason 3; G4 = primary Gleason 4 or 5; R0 = margins negative; R1 = margins positive b Biochemical recurrence-free survival for non-organ confined disease by margin status and Gleason score + Censored log-rank P < Survival probability Follow-up time, months Group 1: R0G3 2: R0G4 3: R1G3 4: R1G4 G3 = primary Gleason 3; G4 = primary Gleason 4 or 5; R0 = margins negative; R1 = margins positive Outcomes from the present series indicate that RARP appears to confer effective long-term oncological control in patients with localised prostate cancer treated at a high-volume centre. While there was pathological Gleason 3+4 disease in 68% and pt3a disease in 34%, only 9.8% of patients undergoing RARP had a BCR, with an 8-year actuarial BCRFS rate of 81%. The strongest predictor of BCR was pathological Gleason grade. To our knowledge, this is the largest report of long-term oncological outcomes in a RARP series to date. BJU International 2013 BJU International 829

7 Sukumar et al. Table 3 Univariable and multivariable models predicting MFS and CSS in 4803 patients undergoing RARP between 2001 and Covariate* Univariable MFS Multivariable MFS Univariable CSS Multivariable CSS No. of events (%) 31 (0.6%) 31 (0.6%) 13 (0.3%) 13 (0.3%) HR (95% CI) P LNs Positive vs negative ( ) ( ) Pathology stage: SVI vs OCD+EPE ( ) 6.64 ( ) ( ) ( ) Pathology primary Gleason: 4 5 vs ( ) 5.36 ( ) ( ) ( ) Preoperative PSA level, ng/ml: >20 vs ( ) Angiolymphatic invasion: Positive vs negative ( ) Margins: Positive vs negative 8.26 ( ) 3.18 ( ) ( ) ( ) 4.70 ( ) ( ) 9.38 ( ) Univariable proportional hazards model for MFS and CSS; Multivariable stepwise proportional hazards model for MFS and CSS; *Significant predictors are in bold; SVI, seminal vesical invasion; EPE, extraprostatic extension. Conflict of Interest None declared. References 1 SiegelR,NaishadhamD,JemalA.Cancer statistics, CA Cancer J Clin 2012; 62: Bill-Axelson A, Holmberg L, Filen F et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. JNatlCancerInst2008; 100: Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. NEnglJMed2011; 364: Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol 2001; 165: Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am 2001; 28: Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 2002; 167: Bianco FJ Jr, Scardino PT, Eastham JA. Radical prostatectomy: long-term cancer control and recovery of sexual and urinary function ( trifecta ). Urology 2005; 66 (Suppl.): Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281: Farkas A, Schneider D, Perrotti M, Cummings KB, Ward WS. National trends in the epidemiology of prostate cancer, 1973 to 1994: evidence for the effectiveness of prostate-specific antigen screening. Urology 1998; 52: Jhaveri FM, Klein EA, Kupelian PA, Zippe C, Levin HS. Declining rates of extracapsular extension after radical prostatectomy: evidence for continued stage migration. J Clin Oncol 1999; 17: Mettlin CJ, Murphy GP, Ho R, Menck HR. TheNationalCancerData Base report on longitudinal observations on prostate cancer. Cancer 1996; 77: Trinh QD, Sammon J, Sun M et al. Perioperative outcomes of robot-assisted radical prostatectomy compared with open radical prostatectomy: results from the nationwide inpatient sample. Eur Urol 2012; 61: Kowalczyk KJ, Levy JM, Caplan CF et al. Temporal national trends of minimally invasive and retropubic radical prostatectomy outcomes from 2003 to 2007: results from the 100% Medicare sample. Eur Urol 2012; 61: Sukumar S, Sammon J, Sun M, Karakiewicz PI, Trinh QD. Adoption of robotic surgery: an analogy from urologic oncology. J Clin Oncol 2012; 30: Badani KK, Kaul S, Menon M. Evolution of robotic radical prostatectomy: assessment after 2766 procedures. Cancer 2007; 110: Menon M, Bhandari M, Gupta N et al. Biochemical recurrence following robot-assisted radical prostatectomy: analysis of 1384 patients with a median 5-year follow-up. Eur Urol 2010; 58: Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. JNatlCancerInst1998; 90: Menon M, Tewari A, Peabody J. Vattikuti Institute prostatectomy: technique. J Urol 2003; 169: Menon M, Tewari A, Baize B, Guillonneau B, Vallancien G. Prospective comparison of radical retropubic prostatectomy and robot-assisted 830 BJU International 2013 BJU International

8 Long-term oncological outcomes after RARP anatomic prostatectomy: the Vattikuti Urology Institute experience. Urology 2002; 60: Menon M, Shrivastava A, Kaul S et al. Vattikuti Institute prostatectomy: contemporary technique and analysis of results. Eur Urol 2007; 51: Menon M, Shrivastava A, Bhandari M, Satyanarayana R, Siva S, Agarwal PK. Vattikuti Institute prostatectomy: technical modifications in Eur Urol 2009; 56: Menon M, Kaul S, Bhandari A, Shrivastava A, Tewari A, Hemal A. Potency following robotic radical prostatectomy: a questionnaire based analysis of outcomes after conventional nerve sparing and prostatic fascia sparing techniques. J Urol 2005; 174: Stamey TA, Yemoto CM, McNeal JE, Sigal BM, Johnstone IM. Prostate cancer is highly predictable: a prognostic equation based on all morphological variables in radical prostatectomy specimens. J Urol 2000; 163: Cookson MS, Aus G, Burnett AL et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 2007; 177: Han M, Partin AW, Piantadosi S, Epstein JI, Walsh PC. Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer. J Urol 2001; 166: Sengupta S, Slezak JM, Blute ML et al. Trends in distribution and prognostic significance of Gleason grades on radical retropubic prostatectomy specimens between 1989 and Cancer 2006; 106: Murphy DG, Kerger M, Crowe H, Peters JS, Costello AJ. Operative details and oncological and functional outcome of robotic-assisted laparoscopic radical prostatectomy: 400 cases with a minimum of 12 months follow-up. Eur Urol 2009; 55: Barocas DA, Salem S, Kordan Y et al. Robotic assisted laparoscopic prostatectomy versus radical retropubic prostatectomy for clinically localized prostate cancer: comparison of short-term biochemical recurrence-free survival. J Urol 2010; 183: Suardi N, Ficarra V, Willemsen P et al. Long-term Biochemical Recurrence Rates After Robot-assisted Radical Prostatectomy: analysis of a Single-center Series of Patients With a Minimum Follow-up of 5 Years. Urology 2012; 79: Sooriakumaran P, Haendler L, Nyberg T et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012; 62: Liss MA, Lusch A, Morales B et al. Robot-assisted radical prostatectomy: 5-year oncological and biochemical outcomes. J Urol 2012; 188: Eastham JA, Scardino PT, Kattan MW. Predicting an optimal outcome after radical prostatectomy: the trifecta nomogram. J Urol 2008; 179: Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol 2004; 172: Guillonneau B, el-fettouh H, Baumert H et al. Laparoscopic radical prostatectomy: oncological evaluation after 1,000 cases a Montsouris Institute. J Urol 2003; 169: Touijer K, Secin FP, Cronin AM et al. Oncologic outcome after laparoscopic radical prostatectomy: 10 years of experience. Eur Urol 2009; 55: Stephenson AJ, Kattan MW, Eastham JA et al. Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era. J Clin Oncol 2009; 27: Correspondence: Akshay Sood,Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, USA. asood1@hfhs.org Abbreviations: BCR(FS), biochemical recurrence (-free survival); BMI, body mass index; CSS, cancer-specific survival; HR, hazard ratio; ((P)LN(D), (pelvic) lymph node (dissection); MFS, metastasis-free survival; OCD, organ-confined disease; RP(O)(RA)RP, (open retropubic) (robot-assisted) radical prostatectomy. BJU International 2013 BJU International 831