Comparative Outcomes of Salvage Retzius-Sparing versus Standard Robotic Prostatectomy: An International, Multi-Surgeon Series.

PURPOSE: Salvage radical prostatectomy is rare due to the risk of postoperative complications. We compare salvage Retzius-sparing robotic assisted radical prostatectomy (SRS-RARP) with salvage standard robotic assisted radical prostatectomy (SS-RARP). MATERIALS AND METHODS: A total of 72 patients across 9 centers were identified (40 SRS-RARP vs 32 SS-RARP). Demographics, perioperative data, and pathological and functional outcomes were compared using Student's t-test and ANOVA. Cox proportional hazard models and Kaplan-Meier curves were constructed to assess risk of incontinence and time to continence. Linear regression models were constructed to investigate postoperative pad use and console time. RESULTS: Median followup was 23 vs 36 months for SRS-RARP vs SS-RARP. Console time and estimated blood loss favored SRS-RARP. There were no differences in complication rates or oncologic outcomes. SRS-RARP had improved continence (78.4% vs 43.8%, p <0.001 for 0-1 pad, 54.1% vs 6.3%, p <0.001 for 0 pad), lower pads per day (0.57 vs 2.03, p <0.001), and earlier return to continence (median 47 vs 180 days, p=0.008). SRS-RARP was associated with decreased incontinence defined as >0-1 pad (HR 0.28, 95% CI 0.10-0.79, p=0.016), although not when defined as >0 pad (HR 0.56, 95% CI 0.31-1.01, p=0.053). On adjusted analysis SRS-RARP was associated with decreased pads per day. Lymph node dissection and primary treatment with stereotactic body radiation therapy were associated with longer console time. CONCLUSIONS: SRS-RARP is a feasible salvage option with significantly improved urinary function outcomes. This may warrant increased utilization of SRS-RARP to manage men who fail nonsurgical primary treatment for prostate cancer.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.

Current Status of Hemostatic Agents and Sealants in Urologic Surgical Practice.

There has been a recent and near exponential increase in the use of hemostatic agents and sealants to supplement the rapidly evolving methods in the surgical management of urologic patients. This article reviews the use of hemostatic agents and sealants in current urologic practice.

Minimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies.

OBJECTIVES: To investigate the long-term outcomes of laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: In all, 1138 patients underwent LRP during a 163-month period from 2000 to 2008, of which 51.5%, 30.3% and 18.2% were categorised into D'Amico risk groups of low-, intermediate- and high-risk, respectively. All intermediate- and high-risk patients were staged by preoperative magnetic resonance imaging or computed tomography and isotope bone scanning, and had a pelvic lymph node dissection (PLND), which was extended after April 2008. The median (range) patient age was 62 (40-78) years; body mass index was 26 (19-44) kg/m(2) ; prostate-specific antigen level was 7.0 (1-50) ng/mL and Gleason score was 6 (6-10). Neurovascular bundle was preservation carried out in 55.3% (bilateral 45.5%; unilateral 9.8%) of patients. RESULTS: The median (range) gland weight was 52 (14-214) g. The median (range) operating time was 177 (78-600) min and PLND was performed in 299 patients (26.3%), of which 54 (18.0%) were extended. The median (range) blood loss was 200 (10-1300) mL, postoperative hospital stay was 3 (2-14) nights and catheterisation time was 14 (1-35) days. The complication rate was 5.2%. The median (range) LN count was 12 (4-26), LN positivity was 0.8% and the median (range) LN involvement was 2 (1-2). There was margin positivity in 13.9% of patients and up-grading in 29.3% and down-grading in 5.3%. While 11.4% of patients had up-staging from T1/2 to T3 and 37.1% had down-staging from T3 to T2. One case (0.09%) was converted to open surgery and six patients were transfused (0.5%). At a mean (range) follow-up of 88.6 (60-120) months, 85.4% of patients were free of biochemical recurrence, 93.8% were continent and 76.6% of previously potent non-diabetic men aged <70 years were potent after bilateral nerve preservation. CONCLUSIONS: The long-term results obtainable from LRP match or exceed those previously published in large contemporary open and robot-assisted surgical series.

Laparoscopic radical prostatectomy for high-risk prostate cancer.

OBJECTIVE: To investigate the results of performing laparoscopic radical prostatectomy (LRP) in patients with high-risk prostate cancer (HRPC): PSA level of ≥20 ng/mL ± biopsy Gleason ≥8 ± clinical T stage ≥2c. PATIENTS AND METHODS: Of a total of 1975 patients having LRP during a 159-month period from 2000 to 2013, 446 (22.6%) had HRPC; all patients were staged by preoperative magnetic resonance imaging or computed tomography and isotope bone scanning. The median (range) patient age was 64.0 (36-79) years; body mass index 27.0 (18-43) kg/m(2) ; PSA level 8.1 (0.1-93) ng/mL and biopsy Gleason 8 (6-10). All patients had a pelvic lymphadenectomy, which was done using an extended template after April 2008 (53.3%). Neurovascular bundle (NVB) preservation was done in 41.5% (bilateral 26.3%; unilateral 15.2%) of patients; an incremental or partial nerve-sparing technique was used in 99 of the 302 (32.8%) NVBs preserved. RESULTS: The median (range) gland weight was 58.5 (20-161) g; operating time 180 (92-330) min; blood loss 200 (10-1400) mL; postoperative hospitalisation 3.0 (2-7) nights; catheterisation time 14 (2-35) days; complication rate 7.6%; lymph node (LN) count 16 (2-51); LN positivity 16.2%; LN involvement 2 (1-8); positive surgical margin (PSM) rate 26.0%; up-grading 2.5%; down-grading 4.3%; up-staging from T1/2 to T3, 24.7%; down-staging from T3 to T1/2, 6.1%. No cases were converted to open surgery and three patients were transfused (0.7%) after surgery. At a mean (range) follow-up of 24.9 (3-120) months, 79.2% of patients were free of biochemical recurrence, 91.8% were continent and 64.4% of previously potent non-diabetic men aged <70 years were potent after bilateral nerve preservation. CONCLUSION: The low morbidity, 55.4% specimen-confinement rate, 26.0% PSM rate, 79.2% biochemical disease-free survival, 91.8% continence rate and 64.4% potency rate, at 35.2 months in the present study serve as evidence firstly that surgery is an effective treatment for patients with HRPC, curing many and representing the first step of multi-modal treatment for others, and that LRP for HRPC appears to be as effective as open RP in this context.

A multinational, multi-institutional study comparing positive surgical margin rates among 22393 open, laparoscopic, and robot-assisted radical prostatectomy patients.

BACKGROUND: Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume. OBJECTIVE: To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. DESIGN, SETTING, AND PARTICIPANTS: Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. RESULTS AND LIMITATIONS: Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload. CONCLUSIONS: This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. PATIENT SUMMARY: In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.

The learning curve for laparoscopic extended pelvic lymphadenectomy for intermediate- and high-risk prostate cancer: implications for compliance with existing guidelines.

OBJECTIVE: To investigate the learning curve for performing extended pelvic lymphadenectomy (ePLND) during laparoscopic radical prostatectomy (LRP) in patients with intermediate- and high-risk prostate cancer. PATIENTS AND METHODS: In all, 500 patients underwent ePLND for intermediate- or high-risk prostate cancer by one surgeon during a 48-month period. A transperitoneal laparoscopic approach was used in all patients to allow adequate access to the internal iliac vessels. The variables chosen as being the most important discriminators of the quality of ePLND were operating time, complication rate and lymph node (LN) yield. The learning curves for ePLND were calculated using the cumulative sum and cumulative average methods and the number of procedures performed until attainment of acceptable failure rates (competence levels) was calculated. LN parameters were compared with the results from the preceding 311 cases where limited PLND was undertaken. RESULTS: The median (range) preoperative PSA level was 8.0(1-62.5) ng/mL and biopsy Gleason score was 7(6-10). In all, 64% of patients had intermediate-risk and 36% had high-risk prostate cancer. There were no intraoperative blood transfusions and no conversions to open surgery. The median (range) blood loss was 200(10-1400) mL and the postoperative transfusion rate was 1.6%. The operating time fell at a steady rate of 2.7% after the 15th case and plateaued after 130 patients. At competence levels of 5% and 10%, the learning curve for all complications ended after 346 and 136 patients, respectively. At a 5% competence level the learning curve for PLND-specific complications was 40 cases and there was no learning curve at a 10% competence level. The overall complication rate was 7.2% of which almost half (47%) were deemed to be PLND-specific. The cumulative average of the LN counts plateaued after 150 procedures. Furthermore, the median LN count after ePLND was more than double that of the authors' historical standard PLND controls (14 vs 6, P < 0.001) and increased with experience up to the end of the series (9 to 20). The likelihood of LN involvement (LNI) correlated with biopsy and pathological Gleason grade, clinical and pathological stage and d'Amico risk group. CONCLUSIONS: This study suggests a learning curve of ≈130 cases for operating time, 136 cases for all complications, 40 cases for PLND-specific complications and 150 cases for LN yield. The risk of LNI for patients with intermediate- and high-risk prostate cancer was 8.4% and 19.4%, respectively, which suggests that a significant proportion would benefit from ePLND. It also shows that ePLND can be safely incorporated into LRP, and therefore also into robot-assisted RP, in a high-volume setting.

Cancer control, continence, and potency after laparoscopic radical prostatectomy beyond the learning and discovery curves.

PURPOSE: To investigate the results of laparoscopic radical prostatectomy (LRP) beyond the learning and discovery curves of 700 patients previously reported by the authors for potency. PATIENTS AND METHODS: Five hundred consecutive patients underwent LRP during a 28-month period with a minimum follow-up of 12 months. Median age (with range) = 61.0 (33-76) years; prostate-specific antigen level = 7.0 (1-37); biopsy Gleason sum = 7 (4-10). Clinical stage was T1 in 41.0%, T2 in 54.2%, and T3 in 4.8%. Nerve preservation (NP) was performed bilaterally in 57.9%, unilaterally in 15.3%, and on neither side in 26.8%. RESULTS: Median operative time was 157 (91-331) minutes, with no conversions or intraoperative blood transfusions; 0.4% of patients received a transfusion postoperatively, and 4.2% had complications. There were no rectal injuries. The overall positive margin rate was 13.0% and correlated with pathologic parameters. At a minimum of 1 year follow-up (mean=13.5 (12-36) mos), overall survival was 100%, and biochemical disease-free survival was 98.8%. The pad-free rate was 97.4%. Potency (International Index of Erectile Function-5 score ≥17) at a mean follow-up of 13.5 months in previously potent men in their 4th, 5th, 6th, and 7th decades after bilateral NP was 100.0%, 91.8%, 82.9%, and 60.0% and after unilateral NP was 100%, 66.7%, 50.1%, and 0.0%. Overall potency after bilateral neurovascular bundle NVB preservation was 86.9%. CONCLUSION: LRP is capable of matching or exceeding the best results for open radical prostatectomy and robot-assisted radical prostatectomy when performed by an experienced surgeon in a high-volume setting. These results suggest that the method used to perform radical prostatectomy is a less important determinant of success than surgical experience.

Initial treatment costs of organ-confined prostate cancer: a general perspective.

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

Extended vs standard pelvic lymphadenectomy during laparoscopic radical prostatectomy for intermediate- and high-risk prostate cancer.

OBJECTIVE: To investigate the effect of extended vs standard pelvic lymphadenectomy (sPLND) for patients with intermediate- and high-risk prostate cancer undergoing laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: Of a total of 1269 patients who underwent LRP during a 109 month period, 374 (30%) had a PLND; 253 men had a sPLND (2000 to March 2008) and 121 had an extended PLND (ePLND; after April 2008) for intermediate- or high-risk prostate cancer. An extraperitoneal approach was used in all patients having sPLND and a transperitoneal approach in patients having ePLND. RESULTS: Patient age, body mass index, gland weight, prostate-specific antigen level and Gleason grade were similar in the two groups. The ePLND group had a greater proportion of patients with cT3 disease (9.9% vs 4.2%, P = 0.046) and was associated with a longer operating time of 206.5 vs 180.0 min (P < 0.001) and a higher node count of 17.5 vs 6.1 (P = 0.002). Blood loss, hospital stay, transfusion and complication rates were similar in the two groups. Lymph node positivity was significantly greater (P = 0.018) in patients with pathological Gleason grade 7 tumours who had ePLND (9.6% vs 1.0%) but was similar for other grades of tumour. CONCLUSION: Based on these findings, and the results of other studies which show a reduction of prostate cancer-specific mortality of 23% if lymph nodes are positive and 15% if they are negative after ePLND, and the correlation between surgical experience, lymph node yield and positivity, we recommend that all patients undergo ePLND if they are being treated with curative intent for intermediate- and high-risk prostate cancer; ePLND should replace sPLND and surgeons performing <35 cases of RP a year should stop performing RP.

Blood loss during laparoscopic radical prostatectomy.

PURPOSE: To determine the impact of a variety of intraoperative parameters that may affect blood loss during laparoscopic radical prostatectomy (LRP). PATIENTS AND METHODS: Intraoperative blood loss was calculated for 757 consecutive LRPs performed by the same surgeon (CE) over a 6-year period. The impact of a number of intraoperative factors that may affect blood loss was studied. These factors include the operative approach (transperitoneal or extraperitoneal), neurovascular bundle (NVB) preservation, lateral prostatic fascia preservation, prostate weight, and the impact of the learning curve for the primary surgeon and trainees. Multivariate and univariate analyses were performed to determine the significance of these factors on intraoperative blood loss during LRP. RESULTS: Mean (+/-standard deviation) blood loss in the 757 patients was 263 +/- 206 mL. Five (0.7%) patients received transfusions. There was a statistically significant difference between extraperitoneal (256 +/- 207 mL) and transperitoneal (308 +/- 199 mL) LRP in terms of blood loss. Nerve preservation [standard or with preservation of the lateral prostatic fascia (LPF)] resulted in a statistically significantly increase in blood loss (205 mL vs 321 mL, respectively, P < 0.001). It also appears that lateral prostatic fascia dissection, as part of a modified NVB preservation, increases blood loss with statistical significance (295 mL vs 353 mL, respectively P < 0.001). There was no statistically significant increase in blood loss with increasing prostate weight (<30 g, 30-50 g, 50-80 g, >80 g). The learning curve also had no impact on blood loss. Trainees were able to perform LRP without an increase in blood loss when mentored by the primary surgeon (CE). CONCLUSION: There was a low requirement for transfusion in this cohort of patients undergoing LRP, and the average blood loss is comparable with the most recently reported minimally invasive prostatectomy series. Blood loss during LRP is mainly affected by nerve preservation, with an average increase of 90 mL for a standard NVB and 150 mL when the lateral prostatic fascia is preserved. It is clear, however, that although NVB preservation may increase blood loss, it does not increase the risk of transfusion for patients or impact on postoperative recovery.

The impact of training on service provision in laparoscopic radical prostatectomy.

OBJECTIVE: To address concerns about the impact of training on patient outcomes during the 'learning curve' for laparoscopic radical prostatectomy (LRP), we compare the results of our patients undergoing LRP with and without trainees performing a substantial proportion of the cases. PATIENTS AND METHODS: In all, 771 consecutive cases of LRP were performed or supervised by one surgeon during a 7.5-year period, of which 114 (15%) were training cases. A five-port transperitoneal technique was used in the first 111 patients and an extraperitoneal approach in the remaining 660. Patient, operative and oncological outcome variables were compared using an independent samples t-test if continuous or with Fisher's exact test for rates. RESULTS: There were no differences in preoperative patient or cancer characteristics with the exception of body mass index (BMI) which was lower in the training cases (medians 25 and 26 kg/m(2), P = 0.02) and patient age which was higher (medians 64 and 62 years, P < 0.001). Operative time, which was longer in training cases (medians 200 and 175 min, P < 0.001) was the only significantly different operative variable between the groups. There were no statistically significant differences in postoperative (duration of catheterization, hospitalization time, complication rates, biochemical recurrence and pad-free rates at 1 year) or pathological (gland weight, positive surgical margin rate) outcomes between the groups. As Fellows did not perform the posterior or apical dissection steps in nerve-sparing cases, no evaluation of potency outcomes is included. CONCLUSIONS: Training cases took a median of 25 min longer to complete than non-training cases. However, other perioperative measures, complications rates and cancer outcomes were similar. Adequately supervised training in LRP does indeed take additional time but is essential for the dissemination of surgical skills and preservation of acceptable outcomes.

The first 1000 cases of laparoscopic radical prostatectomy in the UK: evidence of multiple 'learning curves'.

OBJECTIVE: To report the initial experience of one surgeon, with contemporary experience of both open radical prostatectomy (ORP) and reconstructive laparoscopy, in laparoscopic radical prostatectomy (LRP) in 1000 patients, and to investigate the rate of change of various outcome variables for this procedure with time. PATIENTS AND METHODS: Between March 2000 and December 2007, 1000 consecutive patients with clinical stage T < or = 3aN0M0 prostate cancer underwent LRP, either supervised (17%) or performed (83%), by one surgeon. The median prostate-specific antigen (PSA) level was 7.0 (1-50) ng/mL and median Gleason sum 6 (4-10); the clinical stage was T1 in 46.9%, T2 in 49.8% and T3 in 3.3%. RESULTS: The median (range) operative duration was 177 (78-600) min. There was one conversion (patient 8) to open surgery. The median blood loss was 200 (10-1300) mL and four patients were transfused (0.4%). The median postoperative hospital stay was 3.0 (3-28) nights. The median catheterization time was 10.0 (0.8-120) days. There were 48 complications (4.8%) requiring surgical intervention in 33 (3.3%) patients, 58% of these as a day-case admission. The positive margin rates according to d'Amico risk groups were: low, 9.1%; intermediate, 20.3%; and high, 36.8%. The overall positive margin rate was 13.3%. The PSA level was < or =0.1 mg/L at 3 months in 99.1% of patients. At a mean follow-up of 27.7 (3-72) months, 96.1% of patients were free of biochemical recurrence. In patients with a follow-up of > or =24 months potency rates peaked in the series at 86% for all men and 94% for men aged < or =65 years, and continence rates at 98% before declining thereafter in men with a shorter follow-up. CONCLUSION: The learning curve for operating time and blood loss was overcome within the first 100-150 cases, but complication and continence rates took 150-200 cases to reach a plateau. The longest learning curve was for potency, which did not stabilize until 700 cases. These learning curves are likely to be considerably shorter when surgeons are taught in departments with a high throughput of cases but both surgeons and patients should be aware of them. In view of these findings, the authors recommend that LRP should not be self-taught and should be learned within an immersion teaching programme. Even then, a large surgical volume is likely to be needed to maintain clinical outcomes at the highest level.