Teaching robotic cystectomy: prospective pilot clinical validation of the ERUS training curriculum.

OBJECTIVE: To provide the first clinical validation of the European Association of Urology Robotic Urology Section (ERUS) curriculum for training in robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: The ERUS proposed a structured curriculum, divided into 11 steps, to train novice surgeons and help overcome the steep learning curve associated with iRARC. In this study, one trainee completed the curriculum under the mentorship of an expert. Twenty-one patients were operated on by the trainee following the proposed iRARC curriculum [(t)iRARC group] and were compared with 42 patients treated with the standard of care by the mentor [(m)iRARC group]. To evaluate curriculum safety, peri-operative outcomes, surgical margins and complications were assessed. Propensity-score matching (1:2) was used to identify comparable (t)iRARC and (m)iRARC cases. Matched variables included age, body mass index, neoadjuvant therapy, American Society of Anesthesiologists score and cT stage. Mann-Whitney and chi-squared tests were used to compare peri- and postoperative outcomes between the two cohorts. To evaluate curriculum efficacy, steps attempted and completed by the trainee were assessed and studied as a function of growing surgical experience of the trainee. RESULTS: The trainee progressed in proficiency-based training through steps of increasing difficulty. No differences in estimated blood loss, positive soft tissue margins, number of resected lymph nodes, overall and high-grade complications, or 90-day readmissions between the (t)iRARC and (m)iRARC groups were observed (all P > 0.05). However, operating time was significantly longer in the (t)iRARC group (P = 0.01). Of the 209 available steps, the trainee attempted 168 (80%) and successfully performed 125 (60%). Increasing experience was associated with more steps being successfully performed (P < 0.001). CONCLUSIONS: The proposed ERUS curriculum assists naïve surgeons during the learning curve for iRARC and should be encouraged in order to guarantee optimal outcomes during the learning phase of this procedure.

Timing and delay of radical prostatectomy do not lead to adverse oncologic outcomes: results from a large European cohort at the times of COVID-19 pandemic.

PURPOSE: The current COVID-19 pandemic is transforming our urologic practice and most urologic societies recommend to defer any surgical treatment for prostate cancer (PCa) patients. It is unclear whether a delay between diagnosis and surgical management (i.e., surgical delay) may have a detrimental effect on oncologic outcomes of PCa patients. The aim of the study was to assess the impact of surgical delay on oncologic outcomes. METHODS: Data of 926 men undergoing radical prostatectomy across Europe for intermediate and high-risk PCa according to EAU classification were identified. Multivariable analysis using binary logistic regression and Cox proportional hazard model tested association between surgical delay and upgrading on final pathology, lymph-node invasion (LNI), pathological locally advanced disease (pT3-4 and/or pN1), need for adjuvant therapy, and biochemical recurrence. Kaplan-Meier analysis was used to estimate BCR-free survival after surgery as a function of surgical delay using a 3 month cut-off. RESULTS: Median follow-up and surgical delay were 26 months (IQR 10-40) and 3 months (IQR 2-5), respectively. We did not find any significant association between surgical delay and oncologic outcomes when adjusted to pre- and post-operative variables. The lack of such association was observed across EAU risk categories. CONCLUSION: Delay of several months did not appear to adversely impact oncologic results for intermediate and high-risk PCa, and support an attitude of deferring surgery in line with the current recommendation of urologic societies.

Practical impact of a decision support for goal-directed fluid therapy on protocol adherence: a clinical implementation study in patients undergoing major abdominal surgery.

The purpose of this study was to assess the effects of using a real time clinical decision-support system, "Assisted Fluid Management" (AFM), to guide goal-directed fluid therapy (GDFT) during major abdominal surgery. We compared a group of patients managed using the AFM system with a historical cohort of patients (control group) who had been managed using a manual GDFT strategy. Adherence to the protocol was defined as the relative intraoperative time spent with a stroke volume variation (SVV) < 13%. We hypothesised that patients in the AFM group would have more time during surgery with a SVV < 13% compared to the control group. All patients had a radial arterial line connected to a pulse contour analysis monitor and received a 2 ml/kg/h maintenance crystalloid infusion. Additional 250 ml crystalloid boluses were administered whenever measured SVV ≥ 13% in the control group, and when the software suggested a fluid bolus in the AFM group. We compared 46 AFM-guided patients to 38 controls. Patients in the AFM group spent significantly more time during surgery with a SVV < 13% compared to the control group (median 92% [82, 96] vs. 76% [54, 86]; P < 0.0005), and received less fluid overall (1775 ml [1225, 2425] vs. 2350 ml [1825, 3250]; P = 0.010). The incidence of postoperative complications was comparable in the two groups. Implementation of a decision support system for GDFT guidance resulted in a significantly longer period during surgery with a SVV < 13% with a reduced total amount of fluid administered. Trial registration: Clinical Trials.gov (NCT03141411).

Current trends in patient enrollment for robotic-assisted laparoscopic prostatectomy in Belgium.

BACKGROUND: During the last decade, an inverse stage migration has been observed in radical prostatectomy series at tertiary centers. However, it remains unclear whether similar trends can also be observed in solely robotic practices, including nonreferral centers. The aim of this study was to investigate the clinical and pathological trends in robotic-assisted laparoscopic prostatectomy (RALP) enrollment in Belgium over a period of 6 years through an analysis of a prospective registry. METHODS: A prospective, multicenter database was constructed: consecutive patients undergoing RALP in Belgium from 2010 to 2015 were enrolled, and 7366 men were analyzed. Variations in clinical and pathological variables were explored as a function of the enrollment year with proportional odds for categorical variables and with linear regressions for continuous variables. RESULTS: Net increases were observed in the prostate-specific antigen levels, cT stage, and biopsy Gleason scores across the study years (P < .001). The rate of low-risk prostate cancer (PCa) decreased from 36% in 2010 to 21% in 2015, whereas the rate of intermediate-risk PCa rose from 47% to 58%, and the rate of high-risk PCa rose from 17% to 21%. In parallel, the pT2 stage rate decreased from 76% to 64%, and the rate of Gleason 6 (3 + 3) cases was reduced from 45% to 23% (P < .001). Conversely, the pT3a stage rate rose from 16% to 24%, the pT3b stage rate rose from 7% to 11%, and the rate of Gleason 7 (4 + 3) cases rose from 7% to 21% (P < .0001). Finally, more patients underwent node dissection, and positive lymph nodes were increasingly diagnosed (from 3% in 2010 to 7% in 2015). CONCLUSIONS: During the last 6 years of RALP implementation in Belgium, there was a significant increase in the enrollment of intermediate- and high-risk PCa patients. This yielded a significant increase in adverse pathological characteristics. These results suggest a paradigm shift in PCa treatment, with radical robotic surgery increasing for intermediate- and high-risk patients. Cancer 2017;123:4139-4146. © 2017 American Cancer Society.

Bacillus Calmette-Guerin therapy in non-muscle-invasive bladder carcinoma after renal transplantation for end-stage aristolochic acid nephropathy.

Intravesical instillation of bacillus Calmette-Guerin (BCG) is the treatment of choice for non-muscle-invasive bladder cancer (NMIBC) of high grade and/or carcinoma in situ. This study evaluated the feasibility, efficacy, and tolerance of BCG instillations in eight kidney recipients for end-stage aristolochic acid nephropathy (AAN), a condition at high risk of urothelial carcinoma, and diagnosed for NMIBC. Five of them had relapsed after mitomycin C treatment. Tolerance to BCG was evaluated clinically and regular follow-up with fluorescence cystoscopy was performed along with renal graft function monitoring. Immunosuppression doses were adjusted and prophylactic anti-tuberculous treatment given to reduce risks of graft rejection and infection. After a mean follow-up period of 50 months, seven of the eight patients are free of relapse and kidney graft function remained unchanged. Tolerance was good, except for one episode of fever and one early discontinuation because of subjective discomfort. No systemic tuberculous infection was observed. This is the first clinical observation of successful BCG therapy for NMIBC in patients given transplant for end-stage AAN. Under standardized conditions, immunotherapy based on intravesical BCG is feasible, effective, and well tolerated in renal transplantation.

Long-term evaluation of oncologic and functional outcomes after laparoscopic open-assisted radical cystectomy: a matched-pair analysis.

PURPOSE: To evaluate peri- and postoperative morbidity, and long-term oncologic and functional results of our laparoscopic radical cystectomy (LRC) technique, comparing it with our standard open approach. METHODS: Between 2000 and 2010, 54 patients underwent LRC for urothelial cell carcinoma of the bladder in two academic hospitals. The procedures were performed by two surgeons. Patients were matched 1:1 with patients who underwent open RC in the same years by the same surgical team. Differences in peri- and postoperative complications across the two groups were assessed using Wilcoxon's rank-sum or χ (2) test. Kaplan-Meier curves, log-rank tests and Cox regression models were constructed to assess differences in recurrence-free survival on long-term follow-up between the two groups. RESULTS: Laparoscopic radical cystectomy was significantly associated with lower blood loss (p < 0.0001) and less frequent postoperative ileus (p = 0.03). Regarding more serious postoperative complications, no difference was found across the two cohorts. Median oncologic follow-up was 42 months (IQR 12-72 months) in the LRC cohort and 18 months (IQR 8-27 months) in patients undergoing open radical cystectomy (ORC). No statistically significant difference in recurrence-free survival was observed between the two groups (log rank p = 0.677). On univariate Cox regression, the surgical approach used was not significantly associated with risk of recurrence. CONCLUSIONS: We found that LRC is safe and associated with lower blood loss and decreased postoperative ileus compared with ORC. Moreover, on long-term oncologic follow-up, LRC appeared non-inferior to ORC with no significant difference in recurrence-free survival. Nonetheless, these results must be confirmed by larger series and stronger long-term follow-up data are needed.

Functional Outcomes and Quality of Life in High-risk Prostate Cancer Patients Treated by Robot-assisted Radical Prostatectomy with or Without Adjuvant Treatments.

BACKGROUND: Robot-assisted laparoscopic prostatectomy (RALP) is used frequently to treat prostate cancer; yet, prospective data on the quality of life and functional outcomes are lacking. OBJECTIVE: To assess the quality of life and functional outcomes after radical prostatectomy in different risk groups with or without adjuvant treatments. DESIGN, SETTING, AND PARTICIPANTS: The Be-RALP database is a prospective multicentre database that covers 9235 RALP cases from 2009 until 2016. Of these 9235 patients, 2336 high-risk prostate cancer patients were matched with low/intermediate-risk prostate cancer patients. INTERVENTION: Patients were treated with RALP only or followed by radiotherapy and/or hormone treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a mixed-model analysis to longitudinally analyse quality of life, urinary function, and erectile function between risk groups with or without additional treatments. RESULTS AND LIMITATIONS: Risk group was not significant in predicting quality of life, erectile function, or urinary function after RALP. Postoperative treatment (hormone and/or radiotherapy treatment) was significant in predicting International Index of Erectile Function (IIEF-5), sexual activity, and sexual functioning. CONCLUSIONS: Risk group was not linked with clinically relevant declines in functional outcomes after RALP. The observed functional outcomes and quality of life are in favour of considering RALP for high-risk prostate cancer. Postoperative treatment resulted in lower erectile function measures without clinically relevant changes in quality of life and urinary functions. Hormone therapy seems to have the most prominent negative effects on these outcomes. PATIENT SUMMARY: This study investigated the quality of life, and urinary and erectile function in patients with aggressive and less aggressive prostate cancer after surgery only or in combination with hormones or radiation. We found that quality of life recovers completely, while erectile and urinary function recovers only partially after surgery. Aggressiveness of the disease had a minimal effect on the outcomes; yet, postoperative treatments lowered erectile function further.

18F-JK-PSMA-7 PET/CT for staging intermediate- or high-risk prostate cancer patients before radical prostatectomy: a pilot study.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using radiotracers that bind to the prostate-specific membrane antigen (PSMA) is mainly used in biochemical recurring prostate cancer. The aim of our study was to assess the usefulness of 18F-JK-PSMA-7 PET/CT for local and nodal staging in patients with intermediate- and high-risk prostate cancer (PCa) prior to radical prostatectomy, as compared to conventional imaging techniques. METHODS: We enrolled a total of 10 patients with intermediate- and high-risk PCa diagnosed by multiparametric-MRI followed by systematic and targeted biopsies, eligible for radical prostatectomy with extended lymph node dissection. Clinical team was blind to the results of the pre-surgery 18F-JK-PSMA-7 PET/CT at times of clinical decision and surgery. One month post-surgery, 18F-JK-PSMA-7 PET/CT was repeated and the results of both scans were unblinded. A third 18F-JK-PSMA-7 PET/CT could be acquired at a later time point depending on PSA progression. RESULTS: All pre-surgery 18F-JK-PSMA-7 PET/CT was positive in the prostatic region, while MRI was negative in the prostate in one patient. We also detected positive pelvic lymph nodes in two patients (one high-risk, one intermediate-risk PCa) on pre-surgery and post-surgery 18F-JK-PSMA-7 PET/CT. No positive pelvic lymph nodes were reported on pre-surgical CT and MRI. 18F-JK-PSMA-7 PET/CT detected bladder involvement in one patient and seminal vesicles involvement in two patients; this malignant extension was undetected by the conventional imaging techniques. SUVmax in prostate lesions had an average value of 11.51 (range 6.90-21.49). SUVmean in prostate lesions had an average value of 7.59 (range 5.26-14.02). CONCLUSION: This pilot study indicates that pre-surgery 18F-JK-PSMA-7 PET/CT provides valuable information in intermediate- and high-risk PCa, for surgery planning with curative intent.

Robot-assisted Partial Nephrectomy Using Intra-arterial Renal Hypothermia for Highly Complex Endophytic or Hilar Tumors: Case Series and Description of Surgical Technique.

Background: In partial nephrectomy for highly complex tumors with expected long ischemia time, renal hypothermia can be used to minimize ischemic parenchymal damage. Objective: To describe our case series, surgical technique, and early outcomes for robot-assisted partial nephrectomy (RAPN) using intra-arterial cold perfusion through arteriotomy. Design setting and participants: A retrospective analysis was conducted of ten patients with renal tumors (PADUA score 9-13) undergoing RAPN between March 2020 and March 2023 with intra-arterial cooling because of expected arterial clamping times longer than 25 min. Surgical procedure: Multiport transperitoneal RAPN with full renal mobilization and arterial, venous, and ureteral clamping was performed. After arteriotomy and venotomy, 4°C heparinized saline is administered intravascular through a Fogarty catheter to maintain renal hypothermia while performing RAPN. Measurements: Demographic data, renal function, console and ischemia times, surgical margin status, hospital stay, estimated blood loss, and complications were analyzed. Results and limitations: The median warm and cold ischemia times were 4 min (interquartile range [IQR] 3-7 min) and 60 min (IQR 33-75 min), respectively. The median rewarming ischemia time was 10.5 min (IQR 6.5-23.75 min). The median pre- and postoperative estimated glomerular filtration rate values at least 1 mo after surgery were 90 ml/min (IQR 78.35-90 ml/min) and 86.9 ml/min (IQR 62.08-90 ml/min), respectively. Limitations include small cohort size and short median follow-up (13 [IQR 9.1-32.4] mo). Conclusions: We demonstrate the feasibility and first case series for RAPN using intra-arterial renal hypothermia through arteriotomy. This approach broadens the scope for minimal invasive nephron-sparing surgery in highly complex renal masses. Patient summary: We demonstrate a minimally invasive surgical technique that reduces kidney infarction during complex kidney tumor removal where surrounding healthy kidney tissue is spared. The technique entails arterial cold fluid irrigation, which temporarily decreases renal metabolism and allows more kidneys to be salvaged.

Cost-analysis of robot-assisted radical cystectomy in Europe: A cross-country comparison.

BACKGROUND: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries. METHODS: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient. RESULTS: A total of 490 patients were included. Median operative time was 300(270-360) minutes and median hospital length-of-stay was 11(8-15) days. The average total cost of RARC was 14.794€ (95%CI 14.300-15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments. CONCLUSION: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.

Predictors of trainees' proficiency during the learning curve of robot-assisted radical prostatectomy at high- -volume institutions: results from a multicentric series.

Introduction: The aim of this series was to evaluate predictors of Proficiency score (PS) achievement on a multicentric series of robot-assisted radical prostatectomies (RARP) performed by trainee surgeons with two different surgical techniques at four tertiary-care centers. Material and methods: Four institutional datasets were merged and queried for RARPs performed by surgeons during their learning curve (LC) between 2010 and 2020 using two different approaches (Group A, Retzius-sparing RARP, n = 164; Group B, standard anterograde RARP, n = 79). Logistic regression analysis was performed to identify predictors of PS achievement for the overall trainee cohort. For all analyses, a two-sided p <0.05 was considered significant. Results: Group B showed significantly increased median operative time, positive surgical margins (PSM) status, increased number of nerve-sparing procedures, shorter LC time (each p <0.04). PS, continence status, potency, biochemical recurrence and 1-year trifecta rates were comparable between groups (each p >0.3). On multivariable analysis, time from LC starting ≥12 months (OR = 2.79; 95%IC [1.15-6.76]; p = 0.02) and a nerve-sparing intent (OR = 3.18; 95%IC [1.15-8.77]; p = 0.02) were independent predictors of PS score achievement (Table 3). Conclusions: Higher PS rates for RARP trainees may be expected after 12 months from LC beginning. Short-term training courses are unlikely to confer proper surgical training, while long-term structured training programs seem to be beneficial on perioperative outcomes.

Do perioperative blood transfusions impact oncological outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion? Results from a large multi-institutional registry.

BACKGROUND: Blood transfusions (BT) have been associated with adverse oncologic outcomes in multiple malignancies including open radical cystectomy (ORC) for urothelial carcinoma of the bladder (UCB). Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) delivers similar oncologic outcomes compared to ORC, yet with lower blood loss and reduced transfusions. However, the impact of BT after robotic cystectomy is still unknown. METHODS: This is a multicenter study including patients treated for UCB with RARC and ICUD in 15 academic institutions, between January 2015 and January 2022. BT were administered during surgery (intraoperative blood transfusions, iBT) or during the first 30 days after surgery (post-operative blood transfusions, pBT). The association of iBT and pBT with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were evaluated by univariate and multivariate regression analysis. RESULTS: A total of 635 patients were included in the study. Overall, 35/635 patients (5.51%) received iBT while 70/635 (11.0%) received pBT. After a mean follow-up of 23±18 months, 116 patients (18.3%) had died, including 96 (15.1%) from bladder cancer. Recurrence occurred in 146 patients (23%). iBT were associated with decreased RFS, CSS and OS (P<0.001) on univariate Cox analysis. After adjusting for clinicopathologic covariates, iBT were associated only with the risk of recurrence (HR: 1.7; 95% CI, 1.0-2.8, P=0.04). pBT were not significantly associated to RFS, CSS or OS on univariate and multivariate Cox regression models (P>0.05). CONCLUSIONS: In the present study, patients treated by RARC with ICUD for UCB have a higher risk of recurrence after iBT, yet no significant association with CSS and OS was found. pBT are not associated with worse oncological prognosis.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

Neoadjuvant immunochemotherapy in the treatment of nonmetastatic muscle-invasive bladder cancer: a systematic review.

Introduction: Multiple trials are currently studying the additional effect of immunotherapy on neoadjuvant chemotherapy (NAC) in nonmetastatic muscle-invasive bladder cancer. Methods: We performed a systematic review of the literature that summarizes all ongoing trials, with their results when available. Results: From an initial 269 trials identified, 17 were included. Pathological response and pathological complete response rates of the immunotherapy + NAC combination in the cisplatin-eligible population varied between 56.6-75% and 34.0-66.7%, respectively. Two studies published their results in the cisplatin-ineligible population, with pathological complete response rates of 18 and 45.2%. Conclusion: Neoadjuvant immunochemotherapy in platinum-eligible patients results in response rates higher than those reported for NAC alone. Strong preliminary results are still lacking in the platinum-ineligible population.

When possible, chemotherapy containing cisplatin is recommended before patients undergo radical surgery for bladder cancer. Multiple studies are currently evaluating the additional effect of immunotherapy (drugs that activate the immune system). We reviewed all ongoing studies and found an apparent better control of bladder cancer with the chemotherapy + immunotherapy combination. Stronger studies are needed, however, to confirm these preliminary results. In patients who cannot receive cisplatin, different chemotherapy + immunotherapy combinations were used, but with inconclusive results.

Clinical experience with 18F-JK-PSMA-7 when using a digital PET/CT.

BACKGROUND: Digital PET/CT systems make use of a new technology with higher sensitivity and other better technological features than the analog ones. They require adaptation of the trade-off between performance, tracer dose and acquisition time. The aim of the study was to explore the performance of 18F-JK-PSMA-7 imaging when performed on a digital PET/CT with an adapted protocol, in a population of patients with prostate cancer patients (PCa). Influence of previous therapy on PET/CT performance is generally disregarded in PSMA-based imaging, despite potential influence of hormono-chemotherapy on the target expression. This potential influence was also tested in this work. METHODS: A total of 54 PCa patients experiencing biochemical recurrence were included in the study, in which we analysed the diagnostic performance of digital 18F-JK-PSMA-7 PET/CT. Compared to our protocol applied for acquisition on an analog system, administered dose and acquisition time were reduced by 20% and 50% respectively. We specifically took into consideration the influence of previous treatments on recurrence detection. RESULTS: We detected overall 18F-JK-PSMA-7-positive lesions in 38/54 patients (70.3%). There was no statistically significant difference regarding the detection rate between the groups of patients who had hormono-chemotherapy any time after initial diagnosis and those who never got any hormonal or chemotherapeutic treatment. Regarding the SUV max values, there was not significant difference between the two groups of patients neither in pelvic ganglions nor in other metastatic sites or the prostate region. CONCLUSION: 18F-JK-PSMA7 PET/CT with administered dose and acquisition time adapted to the digital technology provides valuable information in PCa patients with biochemical recurrence.

Defining the Morbidity of Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Adoption of the Comprehensive Complication Index.

Background and Objective: The Clavien-Dindo Classification (CDC) only reports the postoperative complication of highest grade. It is thus of limited value for radical cystectomy, after which patients usually experience multiple complications. The Comprehensive Complication Index (CCI) is a novel scoring system, which incorporates all postoperative events in one single value. The study aimed to adopt the CCI for the evaluation of complications in patients undergoing robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and explore its advantages in the analysis of the morbidity of RARC with ICUD. Patients and Methods: A multicentric cohort of 959 patients undergoing RARC+ICUD between 2015 and 2020, whose complications are encoded in local prospective registries. Postoperative complications at 30 days were assessed using both the CDC and CCI. The CCI was calculated using an online tool (assessurgery.com). Risk factors for overall, major complications (CDC ≥III), and CCI were evaluated using uni- and multivariable logistic and linear regressions. To analyze the potential advantage of using the CCI in clinical trials, a sample size calculation of a hypothetic clinical trial was performed using as endpoint reduction of morbidity with either the CDC or CCI. Results: Overall, 885 postoperative complications were reported in 507 patients (53%). The CCI improved the definition of postoperative morbidity in 22.6% of patients. Male sex and neobladder were associated with major complications and to a significant increase in CCI on adjusted regressions. In a hypothetical clinical trial, 80 patients would be needed to demonstrate a ten-point reduction in CCI, compared with 186 needed to demonstrate an absolute risk reduction of 20% in overall morbidity using the CDC. Conclusion: CCI improves the evaluation of postoperative morbidity by considering the cumulative aspect of complications compared with the CDC. Implementing the CCI for radical cystectomy would help reducing sample sizes in clinical trials. Clinical Trial Registration number: NCT03049410.

Continuing acetylsalicylic acid during Robotic-Assisted Radical Cystectomy with intracorporeal urinary diversion does not increase hemorrhagic complications: results from a large multicentric cohort.

OBJECTIVES: To evaluate whether continuing the antiplatelet drug acetylsalicylic acid≤100mg (ASA) during Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) increases the risk of peri-and postoperative hemorrhagic complications and overall morbidity. Indeed, guidelines recommend interrupting antiplatelet therapy before radical cystectomy; however, RARC with ICUD is associated to reduced estimated blood loss and blood transfusions compared to its open counterpart. METHODS: Data from a multicentric European database were analyzed. All participating centers maintained a prospective database of patients undergoing RARC with ICUD. We identified patients receiving antiplatelet therapy by acetylsalicylic acid ≤100mg. Patients were divided into three groups: those not taking acetylsalicylic acid (no-ASA), those where ASA was continued perioperatively (c-ASA) and those where ASA was interrupted perioperatively (i-ASA). Estimated blood loss and peri-and post-operative transfusions were recorded. Hemorrhagic complications, ischemic, thrombotic and cardiac morbidity was recorded and classified using the Clavien-Dindo score by a senior urologist. RESULTS: 640 patients were analyzed. Patients on acetylsalicylic acid were significantly older and had more comorbidities. No significant difference was found for estimated blood loss between no-ASA, c-ASA and i-ASA (280 vs. 300 vs. 200ml respectively; P = 0.09). Similarly, no significant difference was found for intraoperative (5% vs. 9% vs. 11%; P = 0.07) and postoperative transfusion rate (11% vs. 13% vs. 18%; P = 0.17). Higher ischemic complications were noted in the i-ASA group compared to no-ASA and c-ASA (4% vs. 0.6% vs. 1.4%; P = 0.03). On uni and multivariate logistic regression, continuing acetylsalicylic acid was not significantly associated to either major complications or post-operative transfusions. CONCLUSIONS: Peri-operative acetylsalicylic acid continuation in RARC with ICUD does not increase hemorrhagic complications. Interrupting acetylsalicylic acid peri-operatively may expose patients to a higher risk of ischemic events.

External Validation of a Multiparametric Magnetic Resonance Imaging-based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy.

The nomogram reported by Gandaglia et al (The key combined value of multiparametric magnetic resonance imaging, and magnetic resonance imaging-targeted and concomitant systematic biopsies for the prediction of adverse pathological features in prostate cancer patients undergoing radical prostatectomy. Eur Urol 2020;77:733-41) predicting extracapsular extension (ECE) or seminal vesicle invasion (SVI) has been developed using multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy. We aimed to validate this nomogram externally by analyzing 566 patients harboring prostate cancer diagnosed on MRI-targeted biopsy followed by radical prostatectomy. At final pathology, 37% and 12% patients had ECE and SVI, respectively. Performance of the nomogram, in comparison with the Memorial Sloan Kettering Cancer Center (MSKCC) model and Partin tables, was evaluated using discrimination, calibration, and decision curve analysis. Regarding ECE prediction, the nomogram showed higher discrimination (71.8% vs 69.8%, p = 0.3 and 71.8% vs 61.3%, p < 0.001), and similar miscalibration and net benefit for probability threshold above 30% when compared with MSKCC model and Partin tables, respectively. Performance of the nomogram with regard to SVI was comparable in terms of discrimination (68.5% vs 70.4% vs 67.8%, p ≥ 0.6), presenting a slight overestimation on calibration plots and a net benefit for probability threshold above 7.5%. This is the first multicentric study that externally validates a nomogram predicting ECE and SVI in patients diagnosed with MRI-targeted biopsy. Its performance was less optimistic than expected, and implementation of MRI in this setting was not associated with a clear improvement in patient selection and clinical usefulness when compared with available models. We proposed an updated version of the nomogram predicting ECE using the recalibration method, which leads to an improvement in its performance and needs to be validated in another external set. PATIENT SUMMARY: We validate a prediction tool based on multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy predicting extracapsular extension and seminal vesicle invasion at radical prostatectomy. An improvement of patient selection was not clearly demonstrated when compared with available models based on clinical parameters, and implementation of MRI in this setting still needs to be clarified.

Development and external validation of a nomogram to predict lymph node invasion after robot assisted radical prostatectomy.

BACKGROUND: Prediction of lymph node invasion (LNI) after radical prostatectomy has been rarely assessed in robotically assisted laparoscopic radical prostatectomy (RALP) series. We aimed to develop and externally validate a pretreatment nomogram for the prediction of LNI following RALP in patients with high- and intermediate-risk prostate cancer. METHODS: 1654 RALP patients were prospectively collected between 2009 and 2016 from academic and community hospitals. We included patients with intermediate- and high-risk prostate cancer who underwent pelvic lymph node dissection (e-PLND). Logistic regression analysis was applied to construct a nomogram to predict LNI. Centers were randomly assigned to the training cohort (80%) and validation cohort (20%). The discriminative accuracies were evaluated by the areas under the curve and by the calibration plot. The net benefit of the nomogram to predict LNI was assessed by decision curve analysis and a cut-off was proposed. RESULTS: In total, 14% of the patients in our cohort had pN1 disease. Applying logistic regression analysis, the following covariates were chosen to develop the nomogram: initial PSA, clinical T stage, biopsy Gleason sum, and proportion of positive biopsy cores. The nomogram showed a median discriminative accuracy of 73% and excellent calibration. The net benefit of the model ranged between 7% and 51% predicted risk of LNI. A cut-off to perform e-PLND was set at 7%. This would permit a 29% of avoidable e-PLND, missing 9.4% of patients with LNI. CONCLUSIONS: We developed and externally validated a nomogram to predict LNI in patients treated with RALP from a prospective, multi-institutional, nationwide series. A risk of LNI > 7% is proposed as cut-off above which e-PLND is recommended.

Validated Prospective Assessment of Quality of Life After Robot-Assisted Laparoscopic Prostatectomy: Beyond Continence and Erections.

Continence and erectile function represent major concerns after robot-assisted laparoscopic prostatectomy (RALP), although the analysis of only these results may underestimate the impact of surgery on quality of life (QoL). The aim of the study is to prospectively analyze QoL after RALP according to the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire prostate cancer-specific module (EORTC-QLQ-PR25) and C30 and explore risk factors for the deterioration of QoL after surgery. A total of 584 patients undergoing RALP were prospectively enrolled. QoL was assessed with the validated EORTC-QLQ-PR25 and C30. Differences across QoL items were assessed via Wilcoxon rank-sum test and associations between risk factors and QoL scores were tested via univariate and multivariate linear regression analyses. All items of the PR25 questionnaire showed a significant deterioration at 1 month after RALP and began to normalize 3 months after surgery. At 24 months follow-up, urinary, bowel, and sexual activity scores were not significantly different from preoperative scores, while incontinence aid, treatment-related symptoms, and sexual functioning remained significantly worse. Preoperative sexual activity was more important in determining 3-month sexual outcomes than preoperative 5-item version of the International Index of Erectile Function (IIEF-5) or nerve-sparing approach. An overall return to preoperative QoL was registered at 3 months after RALP in global and physical QoL, and most important, global, physical, social, and role-functioning QoL scores were improved at 12 and 24 months compared to preoperative scores. In this prospective study, detailed data on QoL are reported via the EORTC-PR25 and C30 questionnaires. While urinary, bowel, and sexual activity scores return to baseline values 24 months after surgery, incontinence aid, treatment-related symptoms, and sexual functioning may remain significantly deteriorated. Larger studies are needed to validate these findings.