Author: Toru Kanno, Go Kobori, Masashi Kubota, Satoshi Funada, Takao Haitani, Takashi Okada, Yoshihito Higashi, Seiji Moroi, Hitoshi Yamada

Transcription

1 Accepted Manuscript Title: Standardized and Simplified Retroperitoneal Lymph Node Dissection during Retroperitoneal Laparoscopic Radical Nephroureterectomy for Urothelial Carcinoma of the Upper Ureter or Renal Pelvis: en-bloc Resection Technique Author: Toru Kanno, Go Kobori, Masashi Kubota, Satoshi Funada, Takao Haitani, Takashi Okada, Yoshihito Higashi, Seiji Moroi, Hitoshi Yamada PII: S (17)31186-X DOI: Reference: URL To appear in: Urology Received date: Accepted date: Please cite this article as: Toru Kanno, Go Kobori, Masashi Kubota, Satoshi Funada, Takao Haitani, Takashi Okada, Yoshihito Higashi, Seiji Moroi, Hitoshi Yamada, Standardized and Simplified Retroperitoneal Lymph Node Dissection during Retroperitoneal Laparoscopic Radical Nephroureterectomy for Urothelial Carcinoma of the Upper Ureter or Renal Pelvis: en-bloc Resection Technique, Urology (2017), This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 Standardized and simplified retroperitoneal lymph node dissection during retroperitoneal laparoscopic radical nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis: en-bloc resection technique Toru Kanno a *, Go Kobori b, Masashi Kubota a, Satoshi Funada a, Takao Haitani b, Takashi Okada a, Yoshihito Higashi a, Seiji Moroi b and Hitoshi Yamada a a Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan b Department of Urology, Hamamatsu Rosai Hospital, Hamamatsu, Japan *Correspondence: Toru Kanno, MD, PhD, Department of Urology, Ijinkai Takeda General Hospital, 28-1 Moriminami-cho, Ishida Fushimi-ku, Kyoto , Japan TEL: t.kan@kuhp.kyoto-u.ac.jp Word Counts: Abstract, 249 words; Manuscript text, 2999 words (excluding abstract and references); 2 tables, 2 figures, 2 supplementary figures and 2 videos Page 1 of 31

3 ABSTRACT OBJECTIVE To describe our en-bloc technique of retroperitoneal lymph node dissection (RPLND) during retroperitoneal laparoscopic radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) and evaluate perioperative outcomes. METHODS From 2002 to 2015, 114 patients with UTUC located at the pelvis and/or upper or middle ureter underwent retroperitoneal laparoscopic RNU at two institutions. Performance of RPLND began in February The template of RPLND included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). After incising Gerota s fascia longitudinally, the aorta (left side) or inferior vena cava (right side) was exposed, and the lymphatic and surrounding fatty tissue in the template and kidney was dissected in a single monoblock. Preoperative data were compared between the RPLND and no-rplnd groups using propensity score matching. RESULTS In total, 32 matched pairs were evaluated. RPLND was successfully accomplished without open conversion in all cases. The operative time in the RPLND group was Page 2 of 31

4 approximately 100 minutes longer than that in the no-rplnd group, but there was no significant difference in the blood loss volume or complication rate. The pathological stages were similar in both groups. The mean number of retrieved lymph nodes was 10.7 (range, 3 27), and lymph node metastasis was detected in 5 (16%) cases. CONCLUSION Retroperitoneoscopic en-bloc RPLND permits complete and radical removal of the lymphatic tissue contained in the RPLND template. Our en-bloc technique is a safe and feasible procedure with comparable blood loss and complication rates. Key words: lymph node dissection, upper urinary tract urothelial carcinoma, nephroureterectomy Upper urinary tract urothelial carcinoma (UTUC) is a relatively uncommon cancer, accounting for approximately 5% to 10% of all urothelial carcinomas (1). In general, about 15% to 30% of patients with muscle-invasive UTUC have metastasis in regional lymph nodes. To improve patients survival, lymphadenectomy for UTUC has attracted considerable interest from urologists (2, 3). Although the utility of lymphadenectomy during radical nephroureterectomy (RNU) remains under debate, lymphadenectomy is expected to have a potential role in improving the oncological outcome. Indeed, the Page 3 of 31

5 European Association of Urology (EAU) guideline recommends lymphadenectomy during RNU for invasive UTUC (4). Laparoscopic RNU is a standard treatment option for UTUC. This procedure is now commonly performed because recent data show a tendency toward equivalent oncological outcomes after either laparoscopic or open RNU (4). However, a recent study showed that lymphadenectomy is less commonly performed at the time of laparoscopic RNU. The possible reasons for this are the lack of a standardized template and technical difficulty (5-7). We herein describe our en-bloc technique of retroperitoneal lymph node dissection (RPLND) during retroperitoneal laparoscopic RNU for pelvic tumors and/or upper or middle ureteral tumors with a video. We also analyze the perioperative data and short-term oncologic outcomes of our cohort of patients with RPLND using matched comparisons with patients who did not undergo RPLND during retroperitoneal laparoscopic RNU. Page 4 of 31

6 PATIENTS AND METHODS This study was approved by the institutional review boards at our two institutions. We reviewed our prospectively obtained database of patients who underwent laparoscopic RNU at two institutions from 2002 to During this period, 162 patients underwent laparoscopic RNU. Of these, 48 patients had lower ureteral tumors. For treatment of lower ureteral tumors, the ipsilateral obturator, common iliac, external iliac, and internal iliac lymph nodes were resected by open surgery through a lower abdominal incision when lymph node dissection was performed. Therefore, these 48 patients were excluded from this study. As a result, 114 patients whose tumors were located at the pelvis and/or upper or middle ureter were enrolled in this study. Performance of RPLND during retroperitoneal laparoscopic RNU began in February The indication for laparoscopic RPLND was a good performance status (Eastern Cooperative Oncology Group performance status of 0 or 1) and the absence of apparent retroperitoneal lymph node swelling and severe hydronephrosis. Surgical technique Laparoscopic RNU was performed with a four-port retroperitoneal approach combined with an extraperitoneal lower abdominal midline incision for specimen removal and Page 5 of 31

7 open bladder cuff resection. The template of RPLND was the renal hilar and para-aortic lymph nodes (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side) (Supplementary Figure S1). The cranial border of RPLND was 1 to 2 cm higher than the renal hilum, and the caudal border was the level of the aortic bifurcation. Left-sided RPLND plus RNU (Figure 1) The plane of dissection and its order for the left-sided procedure are shown in Figure 1A. Under general anesthesia, the patient was placed in a 90-degree full flank position, and four laparoscopic ports were placed as described elsewhere for retroperitoneal laparoscopic nephrectomy. Gerota s fascia was incised longitudinally in the general area of the renal hilum and approximately 1 cm anterior to the psoas muscle. Dissection was performed along the psoas muscle, and the left lumbar arteries (L3 4) and left lateral surface of the abdominal aorta were exposed (Fig. 1B). The dissection along the surface of the aorta continued cranially to the left renal artery. The para-aortic lymph node was attached to the left kidney. The left renal artery was clipped and then transected near the aorta using three Hem-o-lok clips (Teleflex, Wayne, PA, USA) (Fig. 1C). Dissection continued toward the left renal vein, which was lying posterior to the left renal artery. Page 6 of 31

8 The left renal vein was then stapled and divided with an Endo GIA stapler (Medtronic, Minneapolis, MN, USA). The left ureter was subsequently secured and clipped with Hem-o-lok clips to prevent tumor spillage. The anterior aspect of the left kidney was mobilized from the underside of the peritoneal envelope. During this procedure, the left adrenal gland was detected and preserved. After the kidney had been fully mobilized, the caudal border of the para-aortic lymph node was clipped and divided. The lymph node was dissected along the aorta, and the inferior mesenteric artery was detected and preserved (Fig. 1D). The left kidney with the para-aortic lymph node was then pulled anterolaterally, clarifying the medial border of the dissected lymph node. The medial border of the para-aortic lymph node was clipped with many Hem-o-lok clips and transected along the aorta (Fig. 1E and F). The monoblock specimen including the left kidney and para-aortic lymph nodes was completely freed, and the patient was moved to the spine position. Removal of the left kidney with the attached para-aortic lymph nodes and open bladder cuff resection was performed via an extraperitoneal lower abdominal midline incision (Fig. 1G). Right-sided RPLND plus RNU (Figure 2) The plane of dissection and its order for the right-sided procedure are shown in Figure Page 7 of 31

9 2A. After incising Gerota s fascia longitudinally, dissection along the psoas muscle and prevertebral plane was performed. Several lumbar veins were coagulated and cut with a vessel-sealing system. As a result, the inferior vena cava (IVC) and retrocaval lymph node was lifted up ventrally. The right lumbar artery and right lateral surface of the aorta were exposed (Fig. 2B). The dissection along the surface of the aorta continued cranially to the right renal artery, which was clipped and transected. The anterior aspect of the right kidney was mobilized from the underside of the peritoneal envelope. The right kidney was taken down, and the right adrenal gland was detected and preserved. The anterior surface of the IVC was incised longitudinally (Fig. 2C). The right vein was exposed, then stapled and divided with an Endo GIA stapler (Fig. 2D). Using the well-established split-and-roll technique, the IVC was circumferentially dissected by transecting the remaining lumbar veins (Fig. 2E). The left renal vein was exposed and preserved (Fig. 2F). The monoblock specimen including the left hilar, paracaval, retrocaval and intra-aortocaval lymph nodes and right kidney was completely freed (Fig. 2G). Follow-up Follow-up included chest and abdominal computed tomography every 6 months for the first 2 years and every year thereafter. Cystoscopy was performed every 3 months for Page 8 of 31

10 the first 2 years and every 6 months to 1 year thereafter. Statistical analysis A standard statistical software package was used (R; Comprehensive R Archive Network [CRAN; Core development team, V.3). Propensity score matching was performed between patients who did and did not undergo RPLND. Patients were matched in a one-to-one fashion by age, side, and American Society of Anesthesiologists (ASA) score. Patients who received preoperative chemotherapy were excluded from this matching analysis. A caliper width of 0.2 of the standard deviation was applied. The chi-square test or Fisher s exact test was used to determine any significant differences in the normal data. A two-tailed Student s t-test was used to analyze differences in continuous variables. The survival curve was calculated by the Kaplan Meier method. A p value of <0.05 was considered significant. Page 9 of 31

11 RESULTS Of 114 patients who underwent retroperitoneal laparoscopic RNU at our institution, 38 patients underwent RPLND and 76 patients did not. Propensity score matching according to age, side, and ASA score was performed to compare perioperative outcomes between the groups with and without RPLND. Only three patients received preoperative chemotherapy, and excluded from this analysis. As a result, 32 matched pairs were available for analysis. Table 1 shows the characteristics of patients with and without RPLND. No significant difference in age, side, ASA score, body mass index, sex, tumor location, or presence of hydronephrosis was found. The tumor was mainly located in the renal pelvis in both groups. To analyze the safety and feasibility of RPLND with laparoscopic RNU, we evaluated the operative time, blood loss, and complication rate (Table 2). The operative time in the RPLND group was approximately 100 minutes longer than that in the no-rplnd group, but there was no significant difference in blood loss. No conversion to open surgery was necessary in either group. With respect to perioperative complications, eight (25%) complications occurred in patients with RPLND, whereas seven (22%) occurred in those without RPLND; however, the difference was not statistically significant (p = Page 10 of 31

12 0.77). Most of the complications in the RPLND group appeared to be related to the lymph node dissections. Chylous ascites was detected due to increased drainage output (median 130 (50-800)ml/day) and milky color of drained fluid after starting oral intake, and the median onset of chylous ascites was three postoperative days. All seven cases were successfully managed conservatively by a low fat diet with or without octreotide. Postoperative pathologic examination revealed that the T stage was similar in both groups and that the rate of pt2 was 59% and 50% in patients with and without RPLND, respectively (p = 0.45). Of 32 patients who underwent RPLND, the mean number of retrieved lymph nodes was 10.7 (range, 3 27), and lymph node metastasis was detected in 5 (16%) cases. Follow-up data were available for all patients. Supplementary Figure S2 shows the extraurothelial recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) curves according to the pathological node status. There were significant differences in RFS, CSS, and OS among the three groups. Notably, no extraurothelial recurrence, including in the regional lymph nodes, occurred in patients with pn0 disease after a median follow-up of 23.0 months (range, 3 72 months), whereas regional lymph node recurrence occurred in four (13%) patients who did not undergo RPLND during RNU after a median follow-up of 38.7 months (range, Page 11 of 31

13 months). Page 12 of 31

14 COMMENT In the present study, we described the surgical steps of our en-bloc resection technique of retroperitoneoscopic RPLND with videos. The retroperitoneal lymph nodes were attached to the kidney in a single monoblock. In terms of perioperative outcomes, blood loss and complications were similar between patients with and without RPLND; however, the operative time was longer in the RPLND group. The role of lymph node dissection for UTUC has been intensively investigated, and both its staging role and therapeutic role have been advocated (8). Lymph node dissection can improve disease staging. Thus, cancer control for UTUC may improve by developing effective adjuvant therapies for node-positive UTUC detected by lymph node dissection (9). A recent large study using the National Cancer Database reported an overall survival benefit in patients who received cisplatin-based adjuvant chemotherapy versus observation after RNU for pn+ UTUC (10). Although controversial, several retrospective studies have also suggested the potential role of lymph node dissection in patients with UTUC (8) (3). It is speculated that accurate and meticulous lymph node dissection could remove some nodal micrometastases not identified on routine pathologic examination, thus improving local control and cancer-specific survival. Page 13 of 31

15 Indeed, the EAU guideline recommends lymphadenectomy during RNU for invasive UTUC (4). The extent of lymph node dissection is an important issue, but anatomic sites for lymph node dissection during RNU have not been clearly defined. The template of lymph node dissection is likely to have a greater impact on patient outcome than the number of lymph nodes removed (3). Interestingly, the anatomic sites of UTUC were recently investigated in three mapping studies to propose anatomic templates of lymph node dissection according to the laterality and tumor location (2, 3). In these mapping studies, the template of UTUC located on the proximal and mid-ureter and renal pelvis included the hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes for the right side and the hilar and para-aortic lymph nodes for the left side. In the present study, we applied the templates advocated by Kondo et al. (3). The safety of laparoscopic RNU has now been demonstrated, and the EAU guideline recommends laparoscopic RNU in T1-T2 tumors because of its efficacy is equivalent to that of open RNU (4). In accordance with this recommendation, the reported rate of laparoscopic RNU was 45.7% (920 of 2016 cases) in Japan (11). However, reports of lymph node dissection for UTUC using minimally invasive approaches are still limited, and a standardized template or technique remains to be established. Indeed, a recent Page 14 of 31

16 study using a nationwide administrative database showed that lymph node dissection was less commonly performed in laparoscopic RNU (10%) than in open RNU (15%) or robotic RNU (27%) (5). During laparoscopic RNU, both the transperitoneal and retroperitoneal approaches are applied. The transperitoneal approach is commonly used in RPLND during minimally invasive RNU, including robotic RNU (12) (13). In contrast, we chose the retroperitoneal approach because we have high-volume experience and are familiar with retroperitoneal laparoscopy. Moreover, although the retroperitoneal approach has less working space, it allows for direct access to the aorta and para-aortic lymph nodes (left side) and IVC and lymph nodes around the IVC (right side). In particular, accessing the retrocaval area by dissecting the lumbar veins and lifting up the IVC is easier than in the transperitoneal approach. This is critical because metastasis to the retrocaval lymph nodes is common in patients with UTUC (3). In accordance with our technique, Abe et al. (14, 15) reported lymph node dissection during retroperitoneal laparoscopic RNU and obtained a good surgical view of the retrocaval area. From the viewpoint of oncologic principles, en-bloc resection is desirable for prevention of tumor dissemination during oncologic surgery. In this respect, the concept of en-bloc resection of the retroperitoneal lymph nodes and kidney in this study is not Page 15 of 31

17 new. However, no previous reports have provided a standardized description of an en-bloc resection technique for RPLND during RNU. We believe that our technique has two merits. First, en-bloc dissection along anatomical landmarks using a template enables radical and complete removal of the lymphatic tissue and surrounding fatty tissue. Second, our technique reduces the disruption of the lymphatic vessels as much as possible. High-grade urothelial carcinoma has high malignant potential, which may explain why local recurrence and port site metastasis are not rare during minimally invasive surgery for urothelial carcinoma, including UTUC (16). We expect that our en-bloc technique will effectively reduce local and port site recurrence by avoiding the dissemination of cancer cells when cancer cells exist in the lymphatic vessels. As for postoperative complications, chylous leakage occurred in seven (22%) patients. Consistent with our results, Kim et al. (17) reported a similar incidence of chylous leakage after laparoscopic lymphadenectomy (10 of 72 cases, 14%). We previously transected the medial border of the para-aortic lymph node using a vessel-sealing system during left-sided RPLND, but we suspected that this procedure could induce inadequate sealing of the resected tissue and chylous leakage. According to the recommendation by Kim et al. (17), we use Hem-o-lock clips when we dissect perihilar and retroperitoneal tissue during RPLND after January Before 2014, seven of 24 Page 16 of 31

18 cases (29%) with RPLND experienced chylous ascites, whereas from January 2014 to September 2017 the rate of chylous ascites decreased to 7% (2 of 27 cases) (p=0.041). Several limitations of the present study should be addressed. First, it was a retrospective study and may therefore be subject to confounding or bias. Second, the sample size of the study was small. Third, era bias exists because the period of groups with or without RPLND were different, and surgical experience was greater for RPLND group. Forth, the follow-up duration in RPLND group was significantly shorter than that in no RPLND group. Therefore, we cannot definitively conclude whether laparoscopic RPLND improves local control and cancer-specific survival. However, the main purpose of this study was to demonstrate feasibility. Because laparoscopic RNU is a standard treatment option and lymphadenectomy is recommended for UTUC, the establishment of a standardized template and technique is valuable for improving treatment outcomes in patients with UTUC. Further studies are needed to evaluate the long-term safety and efficacy of these procedures. Page 17 of 31

19 CONCLUSION Retroperitoneoscopic en-bloc RPLND with the kidney during retroperitoneal laparoscopic RNU permits complete and radical removal of the lymphatic tissue contained in the RPLND template and avoids the spreading of fatty and lymphatic tissue within the surgical field. Our en-bloc technique is a safe and feasible procedure with comparable blood loss and complication rates. Page 18 of 31

20 REFERENCES 1. Alvarez-Maestro M, Rivas JG, Gregorio SA, et al. Current role of lymphadenectomy in the upper tract urothelial carcinoma. Cent European J Urol. 2016;69(4): Seisen T, Shariat SF, Cussenot O, et al. Contemporary role of lymph node dissection at the time of radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol. 2017;35(4): Kondo T, Takagi T, Tanabe K. Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract. World J Clin Oncol. 2015;6(6): Roupret M, Babjuk M, Comperat E, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update. Eur Urol. 2015;68(5): Pearce SM, Pariser JJ, Patel SG, et al. The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy. Urol Oncol Rodriguez J, Packiam VT, Boysen WR, et al. Utilization and Outcomes of Nephroureterectomy for Upper Tract Urothelial Carcinoma by Surgical Approach. J Endourol Moschini M, Foerster B, Abufaraj M, et al. Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy. World J Urol Roscigno M, Brausi M, Heidenreich A, et al. Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer. Eur Urol. 2011;60(4): Leow JJ, Martin-Doyle W, Fay AP, et al. A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol. 2014;66(3): Seisen T, Krasnow RE, Bellmunt J, et al. Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma. J Clin Oncol. 2017;35(8): Miyazaki J, Nishiyama H, Fujimoto H, et al. Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Page 19 of 31

21 Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. J Endourol. 2016;30(5): Melquist JJ, Redrow G, Delacroix S, et al. Comparison of Single-Docking Robotic-Assisted and Traditional Laparoscopy for Retroperitoneal Lymph Node Dissection during Nephroureterectomy with Bladder Cuff Excision for Upper-Tract Urothelial Carcinoma. Urology Aboumohamed AA, Krane LS, Hemal AK. Oncologic outcomes following robot-assisted laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial Carcinoma. J Urol Abe T, Harabayashi T, Shinohara N, et al. Outcome of regional lymph node dissection in conjunction with laparoscopic nephroureterectomy for urothelial carcinoma of the upper urinary tract. J Endourol. 2011;25(5): Abe T, Takada N, Matsumoto R, et al. Outcome of Regional Lymphadenectomy in Accordance With Primary Tumor Location on Laparoscopic Nephroureterectomy for Urothelial Carcinoma of the Upper Urinary Tract: A Prospective Study. J Endourol Roupret M, Smyth G, Irani J, et al. Oncological risk of laparoscopic surgery in urothelial carcinomas. World J Urol. 2009;27(1): Kim BS, Yoo ES, Kim TH, Kwon TG. Chylous ascites as a complication of laparoscopic nephrectomy. J Urol. 2010;184(2): Page 20 of 31

22 Figure 1. Left-sided retroperitoneal lymph node dissection. (a) Schema of the steps during en-bloc dissection of the left-sided retroperitoneal lymph nodes. (b) The aorta and left lumbar artery are exposed. (c) The left renal artery is clipped and transected near the aorta. (d) The inferior mesenteric artery is exposed. (e) The medial border of the retroperitoneal lymph node is exposed by lifting up the left kidney ventrally. The para-aortic lymph nodes are attached to the left kidney. (f) The medial border of the template is clipped and transected. (g) Final specimen. White arrow indicates lymph nodes attached to the left kidney. AA, abdominal aorta; LA, lumbar artery; LRA, left renal artery; LK, left kidney; LN, lymph node; IMA, inferior mesenteric artery. Figure 2. Right-sided retroperitoneal lymph node dissection. (a) Schema of the steps during en-bloc dissection of the right-sided retroperitoneal lymph nodes. (b) The prevertebral plane is dissected and the aorta and left lumbar artery are exposed by lifting the inferior vena cava and retrocaval tissue after transecting several lumbar veins. (c) The surface of the inferior vena cava is exposed by longitudinally incising the tissue on the vena cava. (d) The right renal vein is exposed and transected. (e) The vena cava is dissected circumferentially. (f) The Page 21 of 31

23 left renal vein is exposed and the medial border of the intra-aortocaval lymph node is transected. (g) Final specimen. White arrow indicates lymph nodes resected en bloc with right kidney. AA, abdominal aorta; IVC, inferior vena cava; RLA, right lumbar artery; RK, right kidney; RRV, right renal vein; LN, lymph node; LRV, left renal vein. Supplementary Figure S1. The template of RPLND. Supplementary Figure S2. Kaplan Meier curves of extraurothelial recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to lymph node status. Page 22 of 31

24 Table 1. Preoperative characteristics RPLND (+) RPLND (-) p Value No. pts Mean age ±SD 70.0± ± Mean BMI ±SD 21.7± ± No. side (%) 1 Right 10 (29) 10 (29) Left 25 (71) 25 (71) No. sex (%) 0.43 Men 26 (74) 23 (66) Women 9 (26) 12 (34) Median ASA score (%) (14) 5 (14) 2 28 (80) 28 (80) 3 2 (6) 2 (6) Location of tumor (%) 0.51 Renal pelvis 27 (77) 22 (63) Page 23 of 31

25 Upper ureter 3 (9) 3 (9) Midle ureter 3 (9) 7 (20) Multiple 2 (6) 3 (9) No. preoperative hydronephrosis (%) 22 (63) 19 (54) 0.47 No. preoperative chemotherapy (%) 3 (9) 0 (0) RPLND, retroperitoneal lymph node dissection; SD, standard deviation. Page 24 of 31

26 Table 2. Operative, postoperative, and pathologic outcomes RPLND (+) RPLND (-) p Value Mean surgical mins ±SD 288± ±54 p <0.001 Mean blood loss ±SD 154± ± Median blood loss (range) 124 (0-455) 175 (0-570) No complication (%) 8 (25) 7 (22) 0.77 Lympnocele 1 (3) 0 (0) Chylous ascitis 7 (22) 0 (0) Wound infection 0 (0) 1 (3) Postoperative bleeding 0 (0) 2 (6) Cardiovascular event 0 (0) 1 (3) Incisional hernia 0 (0) 1 (3) Pneumonia 0 (0) 2 (6) Clavien-Dindo (%) 0.25 Ⅰ Ⅰ 2 (6) 0 (0) Ⅱ Ⅱ 6 (19) 4 (13) Ⅲ 0 (0) 2 (6) Ⅳ 0 (0) 0 (0) Ⅴ 0 (0) 1 (3) Ⅲ or greater 0 (0) 3 (9) Pathological stage (%) 0.74 ptis 0 (0) 0 (0) pta 5 (16) 4 (13) pt1 8 (25) 12 (38) pt2 7 (22) 7 (22) pt3 12 (38) 8 (25) pt4 0 (0) 1 (3) pt2 19 (59) 16 (50) 0.45 pn0 27 (84) NA pn1 5 (16) NA No. retrived LNs (range) 10.7±6.4 NA Page 25 of 31

27 NA, not available. (3-27) Page 26 of 31

28 Video 1. Left-sided retroperitoneal lymph node dissection. Video 2. Right-sided retroperitoneal lymph node dissection. Page 27 of 31

29 Kanno T UTUC LND Figure 1_bestsetConverted.png Page 28 of 31

30 Kanno T UTUC LND Figure 2_bestsetConverted.png Page 29 of 31

31 Kanno T UTUC LND Figure S1_bestsetConverted.png Page 30 of 31

32 kanno T UTUC LND revise FigureS2_bestsetConverted.png Page 31 of 31

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