Systematic Review of Open Versus Laparoscopic Versus Robot-assisted Nephroureterectomy

Systematic Review

SyStematic Review Systematic Review of Open Versus Laparoscopic Versus Robot-assisted Nephroureterectomy Emma Mullen, Kamran Ahmed, MBBS, MRCS, PhD, Ben Challacombe, MS, FRCS Urol MRC Centre for Transplantation, King’s College London; Department of Urology, Guy’s and St. Thomas’ NHS Foundation Trust, King’s Health Partners, London, UK Upper tract urothelial carcinoma is a relatively uncommon malignancy. The gold standard treatment for this type of neoplasm is an open radical nephroureterectomy with excision of the bladder cuff. This systematic review compares the perioperative and oncologic outcomes for the open surgical method with the alternative surgical management options of laparoscopic nephroureterectomy and robot-assisted nephroureterectomy (RANU). MEDLINE, EMBASE, PubMed, and Cochrane Library databases were searched using a sensitive search strategy. Article inclusion was then assessed by review of abstracts and full papers were read if more detail was required. In all, 50 eligible studies were identified that looked at perioperative and oncologic outcomes. The range for estimated blood loss when examining observational studies was 296 to 696 mL for open nephroureterectomy (ONU), 130 to 479 mL for laparoscopic nephroureterectomy (LNU), and 50 to 248 mL for RANU. The one randomized controlled trial identified reported estimated blood loss and length of stay results in which LNU was shown to be superior to ONU (P , .001). No statistical significance was found, however, following adjustment for confounding variables. Although statistically insignificant results were found when examining outcomes of RANU studies, they were promising and comparable with LNU and ONU with regard to oncologic outcomes. Results show that laparoscopic techniques are superior to ONU in perioperative results, and the longer-term oncologic outcomes look comparable. There is, however, a paucity of quality evidence regarding ONU, LNU, and RANU; data that address RANU outcomes are particularly scarce. As the robotic field within urology advances, it is hoped that this technique will be investigated further using gold standard research methods. [Rev Urol. 2017;19(1):32-43 doi: 10.3909/riu0691] ® © 2017 MedReviews , LLC 32 • Vol. 19 No. 1 • 2017 • Reviews in Urology Open vs Laparoscopic vs Robot-assisted Nephroureterectomy Key words Urothelial carcinoma • Robot-assisted nephroureterectomy • Open nephroureterectomy • Laparoscopic nephroureterectomy U rothelial carcinomas are a type of transitional epithelium cancer. The majority of urothelial carcinomas affect the lower urinary tract and only approximately 5% to 10% are upper tract neoplasms involving the renal pelvis and ureters.1 The current gold standard treatment for patients with ipsilateral upper tract urothelial malignancy and a normal contralateral kidney is an open radical nephroureterectomy with excision of the bladder cuff.2 The removal of the bladder cuff is of prime importance, as research has shown a high rate of recurrence in the ureteral stump if it is not removed completely.3,4 Management of upper tract urothelial carcinoma (UTUC) has advanced significantly since Le Dentu and Albarran performed the first open nephroureterectomy for UTUC in 1898.5 Surgery has moved toward less invasive procedures that are beneficial for myriad reasons, including faster recovery time and a decreased likelihood of certain intraoperative complications. In 1991 Clayman and colleagues6 performed the first laparoscopic nephroureterectomy; from there, progression to the use of robotic surgery occurred. Use of robotic surgery in urology then led to the first robotic nephrectomy, which took place in 2001 using the Zeus robotic system (Computer Motion, Sunnyvale, CA).7 Following this, the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) was introduced for use in other urologic procedures and, in 2004, the ® first bilateral heminephroureterectomy with robotic assistance took place.8 The aim of this study is to systematically review all relevant literature (randomized and observational studies) on the following surgical modalities of nephroureterectomy: open, laparoscopic, and robot assisted. We performed a comprehensive comparison to assess both perioperative and oncologic outcomes of these types of surgery in order to examine whether one surgical modality is advantageous over another. Methods This study was carried out using guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.9 Database Search and Eligible Studies A sensitive search strategy identified any potentially relevant articles examining the surgical management of UTUC. This search contained words including transitional cell carcinoma and urothelial carcinoma combined with the management options including laparoscop*, open surgery, and robot*. MEDLINE (1946-November 2014), EMBASE (1974-November 2014), Cochrane, and PubMed databases were searched. A list of potentially relevant titles and abstracts were imported to bibliographic software. Duplicates, review articles, non– English-language articles, short surveys, and abstracts from conferences were deleted. Reference lists of articles were checked to identify any missing relevant articles. Study Selection To identify relevant articles, titles and abstracts were read and reviewed. If more detail of a study was required to make a decision of inclusion, then the full article was investigated. Inclusion criteria were that the article must have examined open, laparoscopic, or robot-assisted nephroureterectomy (RANU) surgery. With regard to laparoscopic surgery, all approaches were included: hand-assisted laparoscopy, and transperitoneal or retroperitoneal approaches to surgery. Both the conventional multiport approach and laparoendoscopic single-site approaches to RANU were included in this review. Furthermore, there are a number of different ways in which the distal ureter is handled, all of which were accounted for in this review. For articles to be considered, a minimum sample size of nine was required; otherwise, the statistical power of the study did not reach an acceptable threshold. Endoscopic and laser ablation management were excluded in this review, as these methods are not considered standard treatment of UTUC. Outcomes Examined In this review, the perioperative outcomes of interest were length of time in surgery, estimated blood Vol. 19 No. 1 • 2017 • Reviews in Urology • 33 Open vs Laparoscopic vs Robot-assisted Nephroureterectomy continued Potentially relevant articles identified through database searching n=7191 Additional articles identified after reference review n=3 Articles excluded n=6844 Duplicates n=2053 Irrelevant n=4791 Articles retrieved for full text review n=350 Articles excluded n=300 Full text unavailable n=3 Irrelevant n=297 Articles included in systematic review n=50 Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. loss (EBL), and length of hospital stay. The oncologic outcomes included were cancer-specific survival, overall survival, incidence of malignancy recurrence, and metastases. Results Selection of Studies Overall, 7194 potentially relevant articles were identified, of which 1 was a randomized controlled trial (RCT) and the remainder were observational studies. After removal of duplicates, 5141 articles remained, after which exclusion criteria were applied, leaving 350 articles after abstract review. A full-text review was carried out on these articles; ultimately, 50 were identified for inclusion in the review (Figure 1). Perioperative Outcomes: RCT Following the literature search, one RCT was identified that compared perioperative outcomes and oncologic outcomes of open nephroureterectomy (ONU) versus laparoscopic nephroureterectomy similar, with a difference of only 4 minutes. However, the differences between EBL and length of hospital stay for ONU and LNU were statistically significant (P , .001). This P value showed that LNU was superior to ONU when comparing both surgical outcomes. Comparing the average length of time in surgery, ONU averages ranged from 156.2 to 324.0 minutes, LNU averages ranged from 180.0 to 498.0 minutes, and RANU averages ranged from 184.0 to 326.0 minutes. (LNU) procedures (Table 1).10 The study included 80 patients, of whom 40 were randomly assigned to receive ONU and 40 to receive LNU. The surgery was performed at a single institution by one experienced surgeon. Operative times were very 34 • Vol. 19 No. 1 • 2017 • Reviews in Urology Perioperative Outcomes: Observational Studies In all, 38 observational studies were identified, all of which were retrospective in nature (Table 2). Comparing the average length of time in surgery, ONU averages ranged from 156.211 to Open vs Laparoscopic vs Robot-assisted Nephroureterectomy TABLe 1 Overview of Perioperative Outcomes in Randomized Controlled Trial Study ONU Patients (N) LNU Patients (N) RANU Patients (N) Length of Time in Surgery (min) Estimated Blood Loss (mL) Length of Hospital Stay (d) Simone G et al10 40 40 — 78 vs 82 430 vs 104 3.65 vs 2.3 LNU, laparoscopic nephroureterectomy; ONU, open nephroureterectomy; RANU, robot-assisted nephroureterectomy. 324.012 minutes, LNU averages ranged from 180.013 to 498.014 minutes, and RANU averages ranged from 184.015 to 326.016 minutes. There were a number of studies that directly compared ONU and LNU by designating ONU recipients as the control group and LNU recipients as the case group. In 1995 McDougall and colleagues14 conducted a study in which 13 patients underwent ONU and 10 patients underwent LNU. The outcomes were that the average time for ONU was 234.0 minutes versus 498.0 minutes for LNU; therefore, ONU was the significantly shorter procedure (P 5 .01). Furthermore, another study carried out by Seifman and associates17 in 2001 showed that the ONU procedure was significantly shorter than LNU (ONU, 199.0 min vs. LNU, 320.0 min; P , .001). TABLe 2 Overview of the Observational Study Perioperative Outcomes Study ONU Patients (N) LNU Patients (N) RANU Patients (N) Length of Time in Surgery (min) Estimated Blood Loss (mL) Length of Hospital Stay (d) Aguilera A et al19 70 — 205 vs 189 525 vs 130 8.4 vs 4.5 Ariane M et al33 Blackmur J et al20 Chen C et al34 Chung S et al37 Eandi J et al16 Gill I et al18 Goel A et al42 Greco F et al43 Hattori R et al12 Hemal A et al11 Hemal A et al15 Hu J et al27 Jarrett T et al44 Kamihira O et al45 Kawauchi A et al21 Kitamura H et al26 459 13 — 41 — 35 5 70 36 27 — — — — 34 34 2 5 150 13 33 25 — 42 9 70 53 21 — — 26 1003 34 74a — — — — 11 — — — — — 15 9 — — — — 180 vs 240 194 vs 191 335 212 vs 252 326 282 vs 222 184 vs 188.7 190 vs 240 324 vs 258 156.2 vs 219.2 184 303 329 320 236 vs 233 286 vs 326 — — 223 408 vs 212 200 696 vs 242 — — 665 vs 354 525.88 vs 299.4 103 211 — 232 427 vs 236 475 vs 235 9 vs 8 — 8 9.1 vs 6.5 4.7 6.6 vs 2.3 9.2 vs 5.1 — — 6.88 vs 4.84 2.7 2.3 4 — 21.1 vs 13 14.5 vs 13.5 (Continued) Vol. 19 No. 1 • 2017 • Reviews in Urology • 35 Open vs Laparoscopic vs Robot-assisted Nephroureterectomy continued Study ONU Patients (N) LNU Patients (N) RANU Patients (N) Length of Time in Surgery (min) Estimated Blood Loss (mL) Length of Hospital Stay (d) Lee J et al46 Lim SK25 McDougall E et al14 Muntener M et al47 Nakashima K et al23 Nanigian D et al48 Park SY et al49 Pugh J et al22 — — 13 — 37 — — — 10 — 10 39 36 — 101 — — 38b — — — 10 — 43 225.6 249 234 vs 498 312 289 vs 395 264 221.4 247 187.5 284 — 300 296 vs 497 — 231.7 131 4.75 5.95 11 vs 5 4 — 3 6.3 3 Raman J et al28 Rouprêt M et al50 Schatteman P et al51 Seifman B et al17 Shiong Lee L et al52 Simon SD et al13 Stifelman MD et al53 Taweemonkongsap T et al32 Terakawa T et al54 Trudeau V et al41 Tsujihata M et al55 Yang CK et al24 Yoshino Y et al56 52 26 — 11 — — 11 29 38 20 100 16 31 18 11 31 — — — — — — — — 243 vs 244 — 192 199 vs 320 236 180 232 vs 291 190.6 vs 258.8 478 vs 191 — 234 — 365 160 311 vs 144 313.7 vs 289.3 7.1 vs 4.6 9 vs 4 — 5.2 vs 3.9 7 3.3 6.1 vs 4.6 — 209 vs 346 — 271.2 vs 305.9 251.6 288 — — 557.7 vs 321.5 50.0 304 13.4 vs 9.9 5.83 vs 5.6 — 6.7 — 120 — 24 120 — 1199 715 25 — — — 23 — 20 — aResults from LNU and hand-assisted LNU were averaged to give outcome results. from multiport and laparoendoscopic single-site RANU were averaged to give outcome results. LNU, laparoscopic nephroureterectomy; ONU, open nephroureterectomy; RANU, robot-assisted nephroureterectomy. bResults However, not all studies draw the same conclusions. In 2000 Gill and associates18 found that the LNU procedure was significantly shorter than ONU (ONU, 282 min vs. LNU, 222 min; P 5 .003). Other studies have also demonstrated findings in which LNU is of shorter duration when compared with ONU, including studies by Aguilera and colleagues,19 Blackmur and colleagues,20 Hattori and associates,12 and Kawauchi and associates.21 However, not all of these studies show LNU to be superior to ONU to a suitable degree of significance. No studies were found that directly compared the operating duration of RANU with another method of nephroureterectomy surgery. The largest RANU study that included length of time in surgery as an outcome was by Pugh and coworkers22 from 2007 to 2011. The study took place in three UTUC centers and the average operating time was to 479 mL,23 and for RANU the average range was 5024 to 284 mL.25 Although average ranges of blood loss for each surgical method show overlap, RANU results were superior to other surgical methods. Yang and coworkers24 showed the lowest average EBL of all the studies, at a Although average ranges of blood loss for each surgical method show overlap, RANU results were superior to other surgical methods. 247.0 minutes, which falls within the average time bracket for ONU. EBL was reported in 27 observational studies. The average range of EBL for ONU was 29623 to 696 mL,18 for LNU the average range was 13019 36 • Vol. 19 No. 1 • 2017 • Reviews in Urology total EBL of 50 mL. Although data regarding very few robotic cases have been published, the results of EBL demonstrate the potential benefits of RANU with regard to this perioperative measure. Open vs Laparoscopic vs Robot-assisted Nephroureterectomy TABLe 3 Overview of RCT Oncologic Outcomes Study Type of Surgery Follow-up Period (mo) Simone G et al10 ONU vs LNU 41 Survival/Metastases Rates (%) 5-y CSS: 89.9 vs 79.8 5-y MFS: 77.4 vs 72.5 5-y BTFS: 77.4 vs 72.5 BTFS, bladder tumor-free survival; CSS, cancer-specific survival; LNU, laparoscopic nephroureterectomy; MFS, metastases-free survival; ONU, open nephroureterectomy; RCT, randomized controlled trial. Finally, the last perioperative outcome analyzed was length of stay in hospital. This bears great importance, as it is related to the patient’s general well-being following surgery, and it has implications on the overall total cost of the procedure. The length of stay average for ONU was from 5.217 to 21.121 days, for LNU the average ranged from 2.318 to 13.526 days, and for RANU the average ranged from 2.327 to 6.724 days. The results show that LNU is associated with a shorter hospital stay than ONU. In all of the studies directly comparing the two surgical modalities, the length of stay for patients undergoing LNU was shorter than that for those undergoing ONU. Raman and coworkers28 showed that stay following the procedure was 2.3 days; however, the small study size of nine must be taken into account when considering the statistical power of the study. Oncologic Outcomes: RCT The oncologic outcome results of the one RCT in this category regarding ONU versus LNU were as follows: 5-year cancer-specific survival (CSS), 89.9% versus 79.8%; 5-year metastasis-free survival (MFS), 77.4% versus 72.5%; and 5-year bladder tumor-free survival (BTFS), 77.4% versus 72.5% (Table 3). None of these results were statistically significant; however, the difference in results was most In all of the studies directly comparing the two surgical modalities, the length of stay for patients undergoing LNU was shorter than that for those undergoing ONU. patients undergoing LNU had a significantly shorter length of hospital stay compared with ONU patients (LNU, 4.6 d vs. ONU, 7.1; P , .01). The RANU study that had the shortest average length of stay for patients postoperatively was by Hu and colleagues.27 In this study, the procedure that the patients underwent was a laparoscopic nephrectomy followed by robotic surgery to excise the distal ureter and bladder cuff. The average length of prominent when looking at 5-year MFS with 6 patients having subse- with cancer led to a P value of 0.2 for 5-year CSS, which had no statistical significance. Oncologic Outcomes: Observational Studies Overall, 30 observational studies were found that looked at oncologic outcomes (Table 4); 26 of the studies looked at oncologic outcomes in ONU and LNU procedures, and 4 studies looked at these outcomes in RANU surgery, of which 1 had a reasonable sample size. It is difficult to draw conclusions from overall results, as data were heterogeneous, and many of the studies looked at slightly different outcomes measures across a variety of timescales. However, what was clear from the consensus of the studies was that ONU and LNU were of equal oncologic safety. Few studies were found to address oncologic outcomes with … what was clear from the consensus of the studies was that ONU and LNU were of equal oncologic safety. quent metastasis after ONU and 11 after LNU (P 5 .124). The other results that showed some difference were 5-year CSS rates; 12 cancer-related deaths occurred within the groups, 4 in the ONU group and 8 in the LNU group. This difference in mortality associated regard to RANU; therefore, it is difficult to draw an overall conclusion, but it can be said that the oncologic outcome results compare well with those of ONU and LNU currently. One outcome measure that was commonly reported across Vol. 19 No. 1 • 2017 • Reviews in Urology • 37 Open vs Laparoscopic vs Robot-assisted Nephroureterectomy continued TABLe 4 Overview of the Observational Study Oncologic Outcomes Study Type of Surgery Follow-up Period (mo) Ariane MM et al33 ONU vs LNU 27 (median) Bariol SV et al36 ONU vs LNU ONU: 96 LNU: 101 Blackmur J et al20 ONU vs LNU Capitanio U et al29 ONU vs LNU 49 (median) Chen CH et al34 LNU 9 Chung S et al37 ONU vs LNU Eandi JA et al16 RANU 15.2 El Fettouh H et al57 LNU 25 Fairey AS et al58 ONU vs LNU 26 Favaretto RL et al59 ONU vs LNU 23 Gill IS et al18 ONU vs LNU ONU: 34.4 (mean) LNU: 11.1 (mean) Greco F et al43 ONU vs LNU 60 (median) Survival/Metastases Rates (%) 5-y CSS: 78 vs 90.7 5-y RFS: 50.7 vs 52.2 Metastases during follow-up: 21.1 vs 14 Local recurrence: 15.4 vs 8 Bladder recurrence: 42 vs 28 5-y MFS: 82.1 vs 72 5-y overall survival rate: 73.5 vs 59.1 Progression-free survival: 56.0 vs 24.0 CSS: 73.5 vs 60.9 Bladder cancer recurrence-free survival: 8.7 vs 0 5-y RFS: 76.2 vs 86.8 5-y CSS: 73.1 vs 85.8 Bladder recurrence: 6 Metastasis: 0 Bladder recurrence: 31.7 vs 36 Metastases: 12 vs 8 3-y CSS: 92.4 vs 92 3-y OS: 85.3 vs 92 Recurrence: 36.4 Metastases: 18.2 Bladder recurrence: 24 Metastases: 9 1-year CSS: 92 5-y overall survival rate: 67 vs 68 5-y RFS: 43 vs 33 2-y RFS: 38 vs 42 2-y CSS: 86 vs 82 CSS: 87 vs 97 Bladder recurrence: 37 vs 23 Crude survival: 94 vs 97 Metastases: 13 vs 8.6 5-y DFS: 73 vs 75 (Continued) 38 • Vol. 19 No. 1 • 2017 • Reviews in Urology Open vs Laparoscopic vs Robot-assisted Nephroureterectomy Hattori R et al12 ONU vs LNU ONU: 17 LNU: 31 Hemal AK et al11 ONU vs LNU Hemal AK et al15 RANU Hu JC et al27 RANU Short- term; not specified 16.2 Jarrett T et al44 Kamihira O et al45 LNU LNU Minimum of 12 mo 20 (mean) Kawauchi A et al21 ONU vs LNU ONU: 48.8 LNU: 13.1 Lim SK et al31 RANU 45.5 (median) Manabe D et al35 ONU vs LNU ONU: 28 LNU: 13.6 Muntener M et al47 LNU 74 (median) Park SY et al49 LNU 14 Raman JD et al28 ONU vs LNU Taweemonkongsap T et al32 ONU vs LNU ONU: 51 LNU: 31.7 ONU: 27.9 (mean) LNU: 26.4 (mean) 3-y cause-specific patient survival: 81 vs 80 3-y extravesical recurrencefree rate: 71 vs 71 3-y bladder recurrence-free rate: 51 vs 45 Bladder recurrence: 11.1 vs 9.52 Distant metastases: 11.1 vs 9.52 5-y RFS: 88.8 vs 90.47 5-y CSS: 92.6 vs 95.2 5-y OS: 85.2 vs 85.7 Recurrence: 0 Metastases: 0 Bladder recurrence: 33.3 Metastases: 11.1 Metastases: 12 5-y OS: 70 5-y RFS: 42 Recurrence rate: 47 vs 12 Bladder recurrence: 38 vs 9 2-y OS: 81.3 5-y OS: 60.9 2-y CSS: 87.3 5-y CSS: 75.8 2-y nonurothelial RFS: 71.5 5-y nonurothelial RFS: 68.1 Bladder recurrence: 38 vs 32.8 Distant metastases: 19.9 vs 17.2 2-y DFS: 81.7 vs 75.6 Recurrence rate: 69 5-y OS: 59 CSS: 68 Disease recurrence: 22.8 Mortality: 5.9 TCC recurrence: 50 vs 40 Tumor recurrence: 48.3 vs 35.4 Distant metastases: 6.9 vs 9.7 2-y DSS: 92.5 vs 86.3 (Continued) Vol. 19 No. 1 • 2017 • Reviews in Urology • 39 Open vs Laparoscopic vs Robot-assisted Nephroureterectomy continued Study Type of Surgery Follow-up Period (mo) Survival/Metastases Rates (%) Waldert M et al60 ONU vs LNU 41 Walton TJ et al30 ONU vs LNU 34 (median) Wang XQ et al61 ONU vs LNU 42.4 Yoshino Y et al56 LNU 15 Zou L et al62 ONU vs LNU 53 (median) Recurrent bladder tumors: 27 vs 26 5-y TFS: 76 vs 79 5-y DSS: 80 vs 85 5-y RFS: 73.7 vs 63.4 5-y CSS: 75.4 vs 75.2 3-y RFS: 59.2 vs 62.8 3-y CSS: 80.3 vs 80.7 Recurrence rate: 17.4 Cancer-related deaths: 8.7 1-y CSS: 92.1 vs 95.2 2-y CSS: 87.1 vs 90.5 5-y CSS: 79.2 vs 85.7 CSS, cancer-specific survival; DFS, disease-free survival; DSS, disease-specific survival; LNU, laparoscopic nephroureterectomy; ONU, open nephroureterectomy; OS, overall survival; RANU, robot-assisted nephroureterectomy; RFS, recurrence-free survival. studies was 5-year CSS. The range for 5-year CSS in the ONU category was 73.1% to 92.6%,11,29 for LNU it was 75.2% to 95.2%,11,30 and for RANU just one study looked at this outcome, with a result of 75.8%.31 When looking at metastases rates, the range for ONU was 6.9% to 21.1%,32,33 for LNU the range was 0% to 17.2%34,35 and for RANU the range was 0.0% to 18.2%.15,16 Finally, when looking at bladder cancer recurrence, the range for ONU was 11.1% to 42.0%11,36 and for LNU it was 6.0% to 36.0%34,37; the only RANU study that looked specifically at bladder recurrence was by Hu and coworkers,27 with a result of 33.3%. The study with the largest cohort was carried out by Capitanio and associates29 in 2009, and included 1249 participants. It was a multiinstitutional study with a median follow-up time of 49 months. When data remained unadjusted and were analyzed, ONU compared with LNU was associated with higher recurrence rates and higher cancer-specific mortality (P , .001). However, when results were adjusted for tumor stage there was no statistically significant difference found among the data regarding these outcomes (P 5 .1). This demonstrates clearly how selection bias can influence results when comparing different institutions if potential confounding variables are not adjusted for. Bariol and colleagues36 performed a single-center retrospective study looking at ONU versus LNU, with a follow-up duration of 101 and 96 months, respectively. In this study, the raw data demonstrated LNU was favorable to ONU; bladder tumor recurrence rates were 28.0% versus 42.0%, and 5-year MFS rates were 72.0% versus 82.1%, respectively. However, no statistical significance was shown (P 5 .2 for bladder recurrence and P 5 .26 for 5-year MFS). Finally, the largest robotic study addressing these oncologic outcomes, with 38 participants, was by Lim and associates31; it had a median follow-up of 45.5 months. The overall outcomes in this study were promising; 5-year overall survival was 60.9% and 5-year CSS was 75.8%. The other RANU studies, despite their small sample sizes, also show encouraging results with outcomes that appear to be on par 40 • Vol. 19 No. 1 • 2017 • Reviews in Urology with alternative surgical management options. Discussion This systematic review did confirm that there is a paucity of good-quality evidence regarding ONU, LNU, and RANU procedures, with just one relevant RCT identified. Even though an RCT is considered the highest level of evidence, the one identified must be viewed with caution as it was carried out in a single center by a single surgeon. If this individual surgeon had greater skill and experience in either the ONU or LNU procedure, the results would not be generalizable beyond the single surgeon’s expertise. When examining the perioperative outcome measurement of length of time in surgery, it is expected that, because LNU is a newer technique, it will take longer to complete. However, this value is likely to decrease as a surgeon becomes more skilled and experienced. Results of the other perioperative outcomes of EBL and length of hospital stay showed that LNU was superior to ONU. When interpreting data regarding EBL it Open vs Laparoscopic vs Robot-assisted Nephroureterectomy is important to consider that often volume is defined at the discretion of the surgeon. Therefore, a more objective way of quantifying EBL is to compare preoperative and postoperative hemoglobin levels, (malignancy being at a nonmuscle invasive stage and an absence of metastases) were assigned to the LNU group rather than the ONU group, as LNU was the more novel technique. … a more objective way of quantifying EBL is to compare preoperative and postoperative hemoglobin levels… producing a more valid result. Length of stay is also not easily compared across centers, as it is heavily influenced by patient discharge pathways that are not standardized. Length of stay is also not easy to compare across centers, as it is heavily influenced by patient discharge pathways that are not standardized. Uniform criteria would minimize bias and help in comparing this measure. Some well-accepted advantages of laparoscopic over open surgery for these types of procedures were not examined and must be taken into account, such as postoperative pain. Results were not shown for this outcome in the RCT directly comparing ONU and LNU, but it is expected that the ONU procedure, which is carried out through a flank incision combined with a lower quadrant incision, causes more pain postoperatively than the LNU technique, which uses the four-trocar technique.10 The cosmetic impact of the incisions should also be considered, despite it being a qualitative measure. When exploring oncologic outcomes there were many factors that may have affected result synthesis, including age, pathologic tumor stage or grade, lymphovascular node invasion, and previous malignancies of the bladder. Fortunately, most studies, when processing the results, used multivariable models that adjusted for these potential confounding variables. In the study by Capitanio and associates,29 patients who were at favorable risk One of the most important factors that may have influenced results, particularly concerning malignancy recurrence, is the management of the distal ureter in nephroureterectomy surgery. An abundance of studies examined the controversies of this matter and there is no consensus as to the best available technique; what is clear is that the surgeon operating must adopt a safe technique with good margins.39 Another area of discord surrounds the risk of port-site metastasis in LNU and RANU; however, in a recent review, it was found that the actual risk of this event occurring is low and can be further minimized by using an organ bag when retrieving the specimen.40 It is important to consider the overall cost efficiency of the different surgical procedures, as decisions made regarding the surgical modality for a nephroureterectomy must be economically sustainable. In the study carried out by Trudeau and colleagues41 overall costs of LNU and RANU were compared, taking into account costs of complications, blood transfusions, and length of stay. It was found that a significantly higher cost was incurred during hospitalization if RANU was the chosen procedure. This poses the question of whether RANU is a procedure that should be offered universally from an economic perspective, no matter how good its outcomes are. superior outcomes to those of ONU and, when looking at longer-term oncologic outcomes, results were comparable. However, there are limited studies analyzing the use of RANU, which led to inconclusive results. Studies were all retrospective in nature, with the exception of one; consequently, results should be viewed with caution. RCTs comparing RANU directly with LNU and ONU will be particularly useful to draw further conclusions regarding the procedure with the best outcome. Ultimately, the procedure with the best outcome results will be the most beneficial for patients. There is, however, a significant gap in data regarding the nephroureterectomy procedure; in order to confirm and further review findings, larger, well-designed RCTs are needed. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 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MAin PoinTs • Upper tract urothelial carcinoma is a relatively uncommon malignancy. The gold standard treatment for this type of neoplasm is an open radical nephroureterectomy (ONU) with excision of the bladder cuff. However, surgery has moved toward less invasive procedures, such as laparoscopic nephroureterectomy (LNU) and robotassisted nephroureterectomy (RANU), which are beneficial for myriad reasons, including faster recovery time and a decreased likelihood of certain intraoperative complications. • It is difficult to draw conclusions from overall results, as data were heterogeneous, and many of the studies looked at slightly different outcomes measures across a variety of timescales. However, what was clear from the consensus of the studies was that ONU and LNU were of equal oncologic safety. • When examining perioperative outcomes, the laparoscopic procedures (LNU and RANU) had superior outcomes to those of ONU and, when looking at longer-term oncologic outcomes, results were comparable. Ultimately, the procedure with the best outcome results will be the most beneficial for patients. 42 • Vol. 19 No. 1 • 2017 • Reviews in Urology Open vs Laparoscopic vs Robot-assisted Nephroureterectomy 51. 52. 53. 54. Schatteman P, Chatzopoulos C, Assenmacher C, et al. Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma: results of a Belgian retrospective multicentre survey. Eur Urol. 2007;51:1633-1638. Shiong Lee L, Yip SK, Hong Tan Y, Cheng CW. Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma. Scand J Urol Nephrol. 2006;40:283-288. Stifelman MD, Hyman MJ, Shichman S, Sosa RE. 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