Stesura Seveso Archivio Italiano di Urologia e Andrologia 2021; 93, 4408 ORIGINAL PAPER No conflict of interest declared. location (3). Trying to improve safety and effectiveness of treatment, new techniques such as laparoscopy have become an effective alternative (4-6). The results have shown that both laparoscopic nephroureterectomy and hand-assisted laparoscopic nephroureterectomy had com- parable, if not superior, perioperative and postoperative and similar oncological outcomes (6). Technological advances made to achieve shorter and less morbid operations, have led to the next step of UTUC treatment, which is the use of the robotic platform. Results from multiple studies and the experience of various sur- geons worldwide has shown that RRNU share equivalent oncologic outcomes at short-term follow up, while also displaying very low peri-operative morbidity and compli- cations (7, 8). Although robotic radical nephroureterectomy (RRNU) represents a promising alternative to currently existing methods of treatment, there is a surprising pauci- ty of studies comparing RRNU and ORNU. All available data originate from retrospective studies limited by impor- tant selection biases. Our study represents the first prospective comparison of these two techniques regarding their efficacy and safety in the treatment of UTUC. MATERIALS AND METHODS We enrolled 45 consecutive patients who suffered from non-metastatic, upper urinary tract urothelial carcinoma from September 2019 to March 2021 and underwent rad- ical nephroureterectomy. The surgeries took place in two different academic centres by experienced surgeons. In the former, the operations were performed by three dif- ferent surgeons, each of whom had performed more than 50 open nephroureterectomies. In the latter, all the oper- ations were carried out by the same surgeon with a vast experience in robotic upper tract surgeries (more than 300). Patients were divided in two groups: group A con- sisted of 29 patients (open approach) and group B con- sisted of 16 patients (robotic approach). The exclusion criteria of the patients for the study were the following: patients with history of other urological managements and patients with contraindications for laparoscopic surgery. The Institutional Review Board has approved the study protocol and all patients have signed an informed consent. Purpose: To test the efficacy and safety pro- file of robotic radical nephroureterectomy compared to the open approach. Methods: We enrolled 45 consecutive patients who suffered from non-metastatic, upper urinary tract urothelial carcinoma from September 2019 to March 2021 and underwent radical nephroureterectomy. Patients were divided in two groups: group A consisted of 29 patients (open approach) and group B consist- ed of 16 patients (robotic approach). The factors which were taken into consideration were age, sex, body mass index, tumour size, side and grade, cancer stage, ASA score, operation time, drain removal time, foley time, hospitalization time, esti- mated blood loss, surgical margins, preoperative and postopera- tive creatinine, Hct and bladder recurrences. Statistical analysis was performed with the use of SPSS version 26 and p < 0.05 was the cut-off for reaching statistical significance. Results: The mean age in group 1 was 67.12 years and in group 2 68.12 years, whereas the mean body mass index (BMI) in group 1 was 26.54 kg/m2 and in group 2 25.20 kg/m2. Operative time was better in group A (124 vs 186 mins p < 0.001) and estimated blood loss were better in group B compared to group A (137 vs 316 ml p < 0.001). Length of stay (LOS) was signifi- cantly less in the robotic group (5.75 vs 4.3 days p = 0.003) and the same applied for time required for drain removal (4.5 vs 3.3 days p = 0.006). Conclusions: Robotic radical nephroureterectomy is a safe and efficient alternative to open approach. It provides a favorable perioperative profile in patients suffering from upper urinary tract carcinoma without metastasis. KEY WORDS: Robotic radical nephroureterectomy; Open radical nephroureterectomy; Prospective analysis; Complications. Submitted 31 August 2021; Accepted 13 October 2021 INTRODUCTION Upper urinary tract urothelial carcinoma (UUTC) represents a relatively rare entity, as it accounts for 5% of these neo- plasms with an estimated annual incidence of 2 cases per 100.000 inhabitants (1), but because 60% of these malig- nancies are invasive at the time of diagnosis their manage- ment is of crucial importance (2). According to European Association of Urology, open radical nephroureterectomy (ORNU) with bladder cuff excision remains the gold stan- dard treatment of high-risk UTUC, regardless of tumour Is robotic radical nephroureterectomy a safe alternative to open approach: The first prospective analysis Panagiotis Mourmouris 1, Omer Burak Argun 2, Lazaros Tzelves 1, Mustafa Bilal Tuna 2, Maria Gourtzelidou 1, Andreas Tziotis 1, Ali Riza Kural 1, Andreas Skolarikos 2 1 2nd Department of Urology, Athens Medical School, National and Kapodistrian University of Athens, Sismanogleio General Hospital, Athens, Greece; 2 Department of Urology, Acıbadem Mehmet Ali Aydınlar University, Acibadem Maslak Hospital, Istanbul, Turkey. DOI: 10.4081/aiua.2021.4.408 Summary 409Archivio Italiano di Urologia e Andrologia 2021; 93, 4 Robotic radical nephroureterectomy The Da Vinci Xi System was used for the robotic proce- dures. We followed the same technique for performing RRNU as already published (9). Open NU procedures were based on the standard approach 2 with bladder cuff excision (10). The factors which were taken into consider- ation were age, sex, body mass index, tumour size, side and grade, cancer stage, ASA score, operation time, drain removal time, Foley time, hospitalization time, estimated blood loss, surgical margins, preoperative and postoperative creatinine, Hct and bladder recurrences. Complications were categorized according to Clavien Dindo system (11). Continuous variables are described as mean ± standard deviation (SD) and categorical variables as proportions. Comparison of continuous outcomes was performed using Student’s t-test for normally distributed data and Mann-Whitney test for non-normally distributed data. Distribution of data was checked using the Shapiro-Wilk test. Categorical variables were compared between the two groups, using chi-square and Fisher’s exact test, as dictated by the frequency of observations. Statistical analysis was performed with the use of SPSS version 26 and p ≤ 0.05 was the cut-off for reaching statistical sig- nificance. RESULTS The study included 45 patients from which 7 were female (5 in group A and 2 in group 2) and 38 males. The basic characteristics of the patients are shown in Table 1. The mean age in group 1 was 67.12 years and in group 2 68.12 years, whereas the mean body mass index (BMI) in group 1 was 26.54 kg/m2 and in group 2 25.20 kg/m2, without any statistically significant difference between them. A right sided tumor was found in 13 patients in group A and 4 patients in group B, whereas 14 patients in group A and 10 in group B had tumors in the renal calyces or pelvis. The two groups were matched in terms of ASA score (p = 0.07) and tumor size (p = 0.5). Operative time was better in group A (124 vs 186 mins p < 0.001) and estimated blood loss were better in group B compared to group A (137 vs 316 ml p < 0.001). Two patients in group A and no patient in group B required transfusion. Length of stay (LOS) was significantly less in the robotic group (5.75 vs 4.3 days p = 0.003) and the same applied for time required for drain removal (4.5 vs 3.3 days p = 0.006). The peri- and postoperative results are shown in Table 2. In group A, 16 patients suffered postoperative complications: 7 patients suffered from fever, 2 from hematoma, 3 from wound infection, 2 required transfusion, 1 from paralytic ileus and 1 suffered a myocardial infarction whereas from group B 3 patients suffered postoperative complications, 2 patients with fever and 1 with hematoma. The complications’ classifi- cation according to Clavien-Dindo score is shown in Table 3. DISCUSSION The use of the robotic platform for the management of UUTC has evolved since the first reports of retroperi- toneal (12) and intraabdominal operations (13, 14) that may have also utilized other approaches (open or laparo- scopic) for the nephrectomy or the ureterectomy. The sur- geon’s experience has increased and new “hybrid” tech- niques have emerged, eliminating the basic disadvantage of the robotic platform, namely the need for redocking to perform ureteral excision (15, 16). Robotic approach yielded satisfactory oncological outcomes, even for Table 1. Basic patients characteristics. Group A (n = 29) Group B (n = 16) P value Age (years) 67.12 (12.19) 68.12 (9.0) 0.8 Sex (male/female) 24/5 14/2 1.0 BMI (kg/m2) 26.54 (1.95) 25.20 (1.85) 0.12 Tumor size (mm) 36.2 (20.09) 33.0 (10.73) 0.59 Laterality (right) 13 4 0.71 Tumor location intra renal 14 10 0.06 Ureter 15 6 ASA score 2.56 (0.89) 2.06 (0.25) 0.07 Preoperative creatinine (mg/dl) 1.16 (0.43) 1.23 (0.30) 0.09 Preoperative Hct 38.85 (4.91) 41.71 (3.52) 0.06 ASA score (American Society of Anesthesiologists score); BMI (body mass index). Continuous outcomes are presented as mean values (± standard deviation). Table 3. Post-operative complications. Clavien Dindo classification Group A Group B P value No complications 13 13 0.28 Grade I 12 1 Grade II 3 2 Grade III 0 0 Grade IV 1 0 Grade V 0 0 Table 2. Peri and postoperative outcomes. Group A Group B P value Operative time (min) 124,37 (25.74) 186.25 (34.03) < 0.001 Drain removal time (days) 4.5 (1.21) 3.3 (0,94) 0.006 Foley removal time (days) 11.43 (5.29) 3,37 (0.80) < 0.001 Length of stay (days) 5.75 (1.43) 4.3 (1.08) 0.003 Estimate blood loss (ml) 316.87 (93.87) 137.5 (78.52) < 0.001 Positive surgical margins 8/29 0/16 0.004 Postoperative creatinine (mg/dl) 1.4 (0.47) 1.43 (0.39) 0.8 Postoperative Hct 31.90 (4.37) 37.71 (4.05) 0.003 Pathological T stage 0.01 Ta 5 6 T1 9 2 T2 1 3 T3 13 5 T4 1 0 Tumour grade 0.06 Low grade 8 9 High grade 21 7 Bladder recurrence 3 1 0.33 Archivio Italiano di Urologia e Andrologia 2021; 93, 4 P. Mourmouris, O.Burak Argun, L. Tzelves, et al. 410 advanced disease, with studies reporting a 5-year recur- rence free survival of 57.1% in a series including 28.3% patients with pT3 and 6.7% pT4 disease (17). In the same pace, one of the biggest studies so far enrolling patients from three high volume robotic surgery centers, reported a low high grade complication rate (2.6%) with excellent intra- and post-operative results, suggesting this approach as a viable alternative to the gold standard open approach (18). The technology advancements of the robotic plat- form with the development of the DaVinci Xi system pro- vided the surgeon’s more tools towards increasing experi- ence in this approach, while decreasing operation room time (19). Recently published data in the literature, emphasize the auxiliary role of robotic radical nephroureterectomy in the management of UUTC. The next step was comparing this approach to the open technique, which remains the gold standard therapy according to global guidelines. Available data in existing literature, consist of studies that enrolled patients mainly from open and pure laparoscop- ic approaches, while robotic approach cases in these series represented a minority. Even though some of these studies have large sample sizes, all of them are retrospec- tive and their level of evidence is relatively low, due to the inherited bias of the retrospective nature (20, 21). In another study, multivariate logistic regression revealed a significant favorable impact of robotic approach in post- operative complications but not for intraoperative ones (22). As for the functional outcomes of the procedure, it is documented in the literature that RNU may be a risk factor for acute kidney injury resulting in renal function decline after this procedure (23). In our cohort, in both groups, patients suffered from postoperative creatinine decline, nevertheless when the two groups were com- pared no statistically significant difference was found rel- ative to this factor. A relatively recent study provided data for the oncological superiority of the robotic approach, since this approach showed significantly longer progres- sion free, cancer specific and overall survival (p < 0.05) (6). Nevertheless, in this study the open surgeries were performed in patients of most advanced stage and with negative prognostic factors (like lymph node metastasis). A recent systematic review and meta-analysis of a vast number of patients provided useful insights on the com- parison of the open, laparoscopic, and robotic approach: the RRNU showed the lowest estimated blood loss (EBL) and the ONU the highest (163 ml vs 419.99 ml) with ONU showing higher odds of transfusion. Operative time was shorter for ONU whereas RRNU showed both lower length of stay (LOS) and intraoperative complica- tions. Nevertheless, the meta-analysis is significantly lim- ited from the retrospective studies which were analyzed (only 1 RCT and 2 prospective studies none of which included robotic cases) and most patients included were derived from non-comparative studies. Consequently, in this meta-analysis the distribution is in favor of ONU and LRNU so the data on robotic tech- nique might be weak (24). Our study represents the first prospective comparison between open and robotic approach. The two groups were matched for most significant factors that could affect final outcomes, except from T stage, which it is not like- ly to have an impact to most of perioperative outcomes. We found a favorable profile of the robotic approach when compared to its open counterpart: better LOS, EBL, Hct decrease, need for transfusions and removal of drains and catheters. We also found significant difference in pos- itive surgical margins, but this is possible due to the most advanced stage of tumors that were operated with the open approach. The basic difference from the literature is operation time which was lesser in the open approach but again this can be justified because the robotic approach requests docking of the robot and changing of the instru- ments position for the ureterectomy. The small sample size comprises a limitation of this study, necessitating the conduct of larger prospective cohorts, ideally after patient randomization. Nevertheless, this limitation is partly equilibrated by the prospective nature of our study and the limitation of potential biases that it provides. Another potential limitation is the relatively short follow-up (1-5 months), but the study was designed to address the efficacy and safety of these procedures by comparing their perioperative outcomes. 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Correspondence Panagiotis Mourmouris, MD, PhD (Corresponding Author) thodoros13@yahoo.com Lazaros Tzelves, MD lazarostzelves@gmail.com Maria Gourtzelidou, MD mariaeirinigr@gmail.com Andreas Tziotis, MD tziotis.and@gmail.com Andreas Skolarikos, PhD andskol@yahoo.com 2nd Department of Urology, Athens Medical School, National and Kapodistrian University of Athens, Sismanogleio General Hospital, Athens (Greece) Omer Burak Argun, MD drburakargun@gmail.com Mustafa Bilal Tuna, MD mustafabilaltuna@gmail.com Ali Riza Kural, PhD arkural@gmail.com Department of Urology, Acıbadem Mehmet Ali Aydınlar University, Acibadem Maslak Hospital, Istanbul (Turkey)