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Keywords:

  • transitional cell carcinoma;
  • nephroureterectomy;
  • laparoscopy;
  • minimally invasive techniques;
  • ureterectomy

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

What's known on the subject? and What does the study add?

Upper urinary tract transitional cell carcinoma (UUT-TCC) is an aggressive disease. The mainstay in the treatment of UUT-TCC is surgical intervention, with oncological control the primary objective. UUT-TCCs have been conventionally treated with radical nephroureterectomy (NU). This procedure involves removal of the kidney, ureter and ipsilateral excision of a bladder cuff. Whilst open NU has traditionally been the approach used, laparoscopic NU (LNU) is now an increasingly popular and established approach for UUT-TCC. It is argued that LNU reduces postoperative morbidity without compromising oncological efficacy. With technological evolution, robotic NU has now been attempted in some centres as well. In addition, several techniques have been described to manage the bladder cuff with no agreement as to the most efficacious approach. In a further attempt to reduce morbidity and safeguard nephrons, there have been advocates of a number of nephron-sparing techniques, e.g. ureteroscopic management, percutaneous approaches, and distal ureterectomy. These approaches obviously raise concern on oncological efficacy with requirement for more stringent long-term surveillance protocols.

This study comprehensively reviews and summarises the evidence comparing various surgical techniques in the management of UUT-TCC. The review additionally evaluates and critically appraises the quality of evidence available, which currently informs practice.

  • • 
    Surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC) has significantly changed over the past two decades. Data for several new surgical techniques, including nephron-sparing surgery (NSS), is emerging.
  • • 
    The study systematically reviewed the literature comparing (randomised and observational studies) surgical and oncological outcomes for various surgical techniques
  • • 
    MEDLINE, EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed were searched to identify suitable studies. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team.
  • • 
    The data analysis was performed using the Cochrane software Review manager version 5. Comparable data from each study was combined in a meta-analysis where possible. For dichotomous data, odds ratios with 95% confidence intervals (CIs) were estimated based on the fixed-effects model and according to an intention-to-treat analysis. If the data available were deemed not suitable for a meta-analysis it was described in a narrative fashion.
  • • 
    One randomised control trial (RCT) and 19 observational studies comparing open nephroureterectomy (ONU) and laparoscopic NU (LNU) were identified. The RCT reported the LNU group to have statistically significantly less blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge (2.30 vs 3.65 days, P < 0.001) than the ONU group. At a median follow-up of 44 months, the overall 5-year cancer-specific survival (CSS; 89.9 vs 79.8%) and 5-year metastasis-free survival rates (77.4 vs 72.5%) for the ONU were better than for LNU, respectively, although not statistically significant.
  • • 
    A meta-analysis of the observational studies favoured LNU group for lower urinary recurrence (P < 0.001) and distant metastasis. The meta-analyses for local recurrence for the two groups were comparable.
  • • 
    One retrospective study comparing ONU with a percutaneous approach for grade 2 disease reported no significant differences in CSS rates (53.8 vs 53.3 months).
  • • 
    Three retrospective studies compared NSS and radical NU, and reported no significant differences in overall CSS and recurrence-free survival between the two approaches.
  • • 
    Five retrospective studies compared various techniques of en bloc excision of the lower ureter. No technique was reported to be better (operative and oncological) than any other.
  • • 
    This review concludes that there is a paucity of good quality evidence for the various surgical approaches for UUT-TCC. The techniques have been assessed and reported in many retrospective single-centre studies favouring LNU for better perioperative outcomes and comparable oncological safety. The reported observational studies data is further supported by one RCT.

Abbreviations
CSS

cancer-specific survival

NSS

nephron-sparing surgery

(L)(O)NU

(laparoscopic) (open) nephroureterectomy

OR

odds ratio

OS

overall survival

PFS

progression-free survival

RCT

randomised control trial

RFS

recurrence-free survival

STROBE

the Strengthening the Reporting of Observational Studies in Epidemiology

UUT-TCC

upper urinary tract TCC

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

Upper urinary tract TCCs (UUT-TCCs) are uncommon and aggressive tumours. For clinically localised disease, surgical excision in the form of radical nephroureterectomy (NU) is considered as ‘standard of care’. The procedure entails en bloc excision of the kidney, ureter and an ipsilateral cuff of the urinary bladder around the ureteric orifice. Major resections such as this, are not uncommonly associated with significant morbidity in the form of blood loss, postoperative pain and therefore prolonged hospitalisation. To mitigate some of the morbidity, there has been considerable advancement in minimally invasive techniques, with a clear focus on reducing blood loss, length of incision, postoperative pain, hospital stay and earlier convalescence. As a result, many viable alternates to open NU (ONU) are offered including laparoscopic NU (LNU), ureteroscopic resection/fulguration, and segmental resection or percutaneous management. However, the fundamental goal in surgical resection of cancer is oncological control and this should not be compromised at the cost of better immediate operative outcomes. Since the development of minimally invasive techniques in the surgical management of UUT-TCC there has been a considerable amount of evidence published comparing various surgical techniques; reporting on both immediate operative and oncological outcomes. Despite advances in surgical techniques and technologies many uncertainties continue to exist in clinical practice.

The aim of the present study was to systematically review the literature (randomised and observational studies) on the comparative surgical approaches in the management of UUT-TCC and comprehensively present the reported clinical data. Comparisons included radical ONU vs LNU, NU vs conservative localised ureter resection, open surgical resection (local or NU) vs endoscopic management and surveillance, and open surgical handling of lower ureter end compared with endoscopic- or laparoscopic-assisted methods.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

A sensitive search strategy was developed for MEDLINE to identify published clinical studies that compared different surgical techniques for treating UUT-TCC. Specific search terms were used in conjunction with the Cochrane highly sensitive search strategy for randomised control trials (RCTs). Other databases searched included EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed. A list of titles and abstracts of potentially relevant clinical studies were generated by the search strategy and imported in to bibliographic software (EndNote®). This list was screened by two authors independently (B.R. and B.S.) and fully published papers were retrieved where appropriate. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team.

The primary outcomes of interest were surgical outcomes, e.g. operative duration, blood loss, and hospital stay. Secondary outcomes included oncological safety, e.g. bladder tumour recurrence, local recurrence, and the development of metastases, recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). The extracted data included information on trial design, participants, types of interventions, and outcome measures. Data analyses compared radical surgery with other primary surgical methods and comparisons were made for each of the outcomes. Also, comparisons were made between different surgical approaches.

The data analysis was performed using the Cochrane software Review Manager version 5. Comparable data from each study were combined in a meta-analysis where possible. For dichotomous data, odds ratios (ORs) with 95% CIs were estimated based on the fixed-effects model and according to an intention-to-treat analysis. If the data available were deemed not suitable for a meta-analysis it was described in a narrative fashion.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

Of the 400 potentially relevant publications identified and screened for retrieval, only one RCT was identified, which compared early surgical and oncological outcomes between LNU and ONU [1]. In all, 32 observational studies comparing ONU and LNU [2–24]; five comparing various techniques to deal with the lower end of the ureter [25–29], three comparing nephron-sparing surgery (NSS) with radical NU [30–32] and one comparing radical NU with percutaneous approaches were also identified [33] (Fig. 1). A risk of bias graph for the single identified RCT was generated (Fig. 2). A quality assessment of the observational studies comparing ONU and LNU was performed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Table 1).

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Figure 1. Studies identification in the review.

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Figure 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.

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Table 1. Observational studies comparing ONU and LNU: quality assessment using STROBE guidelines
StudyDesignTechnique for lower ureter, -ONU/LNUABCDEFGHI
  1. A, Objectives and pre-specified hypothesis in the introduction; B, Eligibility criteria of cohort in methods; C, Methods for recruitment of participant; D, Mention of outcomes, exposure, and confounder; E, Study size calculated; F, Potential biases addressed; G, Statistical methods described; H, Mention of how missing data was handled; I, Limitation of the study and the generalisations mentioned; Y, Yes; N, No; P, Partially. TUR, transurethral resection.

Gill et al. 2000 [2]RetrospectiveOpen bladder cuff/transvesical detachmentPNNPYNYNP
Shalhav et al. 2000 [3]RetrospectiveOpen bladder cuff/extravesical staplingPNNPYNYNP
Stifelman et al. 2001 [4]RetrospectiveOpen bladder cuff/transvesical detachment         
Goel et al. 2002 [5]RetrospectiveOpen bladder cuff/open bladder cuffPNNPYNYNP
Matsui et al. 2002 [6]RetrospectiveOpen bladder cuff/open bladder cuffYPNPYNYNP
Kawauchi et al. 2003 [7]RetrospectiveOpen bladder cuff or TUR/open bladder cuff or TURPNNPYNYNP
Klinger et al. 2003 [8]Unclear if retrospective or prospectiveOpen bladder cuff/open bladder cuffYNNPYNYNP
Hsueh et al. 2004 [9]RetrospectiveOpen bladder cuff/open bladder cuffYNNPYNYNP
Rassweiler et al. 2004 [11]RetrospectiveOpen bladder cuff/open bladder cuffPNNPYNYNP
Hattori et al. 2006 [12]Unclear if retrospective or prospectiveOpen/lap or openYNPPYNYNP
Raman et al. 2006 [13]RetrospectiveOpen-intravesical/extravesical techniques or TUR de-roofing/open-intravesical/extravesical techniques or TUR de-roofingPNNYYPYNP
Rouprêt et al. 2007 [14]RetrospectiveOpen bladder cuff/open bladder cuffYPNYYPYNY
Manabe et al. 2007 [15]RetrospectiveOpen bladder cuff/open-intravesical/extravesical techniquesYNNPYNYNP
Hsueh et al. 2007 [10]RetrospectiveOpen bladder cuff/open bladder cuffYNNYYNYNP
Taweemonkongsap et al. 2008 [17]RetrospectiveOpen bladder cuff/open bladder cuffYNNPYNYNY
Hemal et al. 2008 [16]RetrospectiveOpen bladder cuff/open bladder cuff or laparoscopic stapling using Endo-GIA device or laparoscopic excision with scissors and free hand intracorporeal suturing or ‘pluck’ techniqueYNNPYNYNP
Waldert et al. 2009 [18]RetrospectiveOpen bladder cuff/open bladder cuffYPNYYNYNP
Capitanio et al. 2009 [19]Retrospective multicentre studyWithout excision of a bladder cuff or open or laparoscopic cuff excision or cuff excision via endoscopy/without excision of a bladder cuff or open or laparoscopic cuff excision or cuff excision via endoscopyYNNYYYYNY
Greco et al. 2009 [20]Unclear if retrospective or prospectiveOpen bladder cuff/laparoscopic approachYNNYYNYNP
Favaretto et al. 2010 [21]RetrospectiveOpen bladder cuff/open or laparoscopic or TURYYPYYYYNY
Stewart et al. 2011 [23]RetrospectiveExtra- or transvesical mobilisation of the lower ureter and bladder cuff/‘pluck’ technique or formal open cystotomy, and combined extra- and transvesical dissectionYNNYYPYNP
Ariane et al. 2011 [22]Retrospective multicentre studyOpen bladder cuff or ‘pluck’/open bladder cuff or ‘pluck’YNNYYPYNP
Walton et al. 2011 [24]Retrospective multicentre studyAbercrombie technique or bladder cuff excision/Abercrombie technique or bladder cuff excisionYNNYYYYNY

RCT OF LNU VS ONU

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

This review identified one RCT comparing perioperative and oncological outcomes between LNU and ONU [1], it was a single institutional study with all procedures (both ONU and LNU) undertaken by one experienced surgeon. In all, 40 patients with non-metastatic UUT-TCC were recruited for both the approaches. Perioperative outcomes were compared using Student's t-test and oncological outcomes were compared using the log-rank test. Further analysis was performed after stratification by grade and stage. This trial showed that LNU had statistically significantly better outcomes for blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge from hospital (2.30 vs 3.65 days, P < 0.001) than ONU. At a median follow-up of 44 months, the overall 5-year CSS (89.9 vs 79.8%) and 5-year metastasis-free survival rates (77.4 vs 72.5% for ONU vs LNU) were seemingly better for LNU but not statistically significant. The bladder tumour-free rates for the two groups were similar.

OBSERVATIONAL STUDIES COMPARING LNU VS ONU

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

SURGICAL OUTCOMES

Observational data from 19 studies suggest that laparoscopic surgical interventions either complete or combined with open excision of the lower end, reduced intraoperative blood loss, postoperative pain, and hospital stay compared with open surgery [2–9,11–14,17,18,20–23,34] (Table 2). There was lack of consistency in reporting data including statistical methods. In all, 16 studies reported primary surgical outcomes as means [2–9,11–14,17,18,20,21,23,34], while three contemporary studies reported primary surgical outcomes as medians [21–23]. The range of mean blood loss for the LNU and ONU groups was 144–580 mL and 299.6–750 mL, respectively. The range of mean hospital stay for the LNU and ONU groups was 2.3–13 days and 4.2–21.1 days, respectively. The operative duration appears to be longer in the LNU groups, as the range of mean operative durations for the LNU and ONU groups was 164.8–462 min and 156.2–324 min, respectively. Only four studies reported a better operating time with LNU [8,12,35].

Table 2. Early surgical outcomes from observational studies for LNU vs ONU
StudyOperative duration, mean, minBlood loss Mean, mLHospital stay Mean, days
Gill et al. 2000 [2]224.8 vs 280.2242 vs 6962.3 vs 6.6
Shalhav et al. 2000 [3]462 vs 234199 vs 4416.1 vs 12
Stifelman et al. 2001 [4]291 vs 232144 vs 3114.6 vs 6.1
Goel et al. 2002 [5]189 vs 184275 vs 5705.1 vs 9.2
Matsui et al. 2002 [6]286.8 vs 239.5151 vs 299.62.7 vs 4.2
Kawauchi et al. 2003 [7]233 vs 236236 vs 42713 vs 21.1
Klinger et al. 2003 [8]198 vs 220282 vs 5328.1 vs 13.3
Hsueh et al. 2004 [9]259.1 vs 230.2410 vs 7509.3 vs 12.6
Rassweiler et al. 2004 [11]200 vs 188450 vs 60010 vs 13
Hattori et al. 2006 [12]Pure LNU vs. Combined LNU vs. ONU258 vs 306 vs 324354 vs 580 vs665 
Raman et al. 2006 [13]244 vs 243191 vs 4784.6 vs 7.1
Rouprêt et al. 2007 [14]164.8 vs 155.2274.5 vs 337.73.7 vs 9.2
Taweemonkongsap et al. 2008 [17]258.9 vs 190.7289.4 vs. 313.89.32 vs 8.69
Hemal et al. 2008 [16]219.2 vs 156. 2299.4 vs. 525.884.84 vs 6.88
Waldert et al. 2009 [18]220 vs212300 vs. 5428.1 vs13.8
Greco et al. 2009 [20]240 vs190
Favaretto et al. 2010 [21]265 vs164 (median)200 vs.250 (median)3 vs 5 (median)
Stewart et al. 2011 [23]165 vs180 (median)280 vs 398 (median)7 vs 10 (median)
Ariane et al. 2011 [22]240 vs 180 (median)8 vs 9 (median)

SECONDARY ONCOLOGICAL OUTCOMES

Meta-analysis was performed on observational studies reporting lower urinary tract (bladder and urethra) recurrence, local recurrence and distant metastasis. In all, 17 observational studies reported on lower urinary tract recurrence [2,3,5,7,9–15,17,18,20,21,23,36], 15 on local recurrence [2,3,5,7,9–13,15,17,18,23,36] and 16 on distant metastasis [2,3,5,7,9–15,17,18,22,23,36]. The pooled OR between the LNU and ONU approaches for lower urinary tract recurrence favoured the LNU group (OR 0.64, 95% CI 0.50–0.82, P < 0.001; Fig. 3). The pooled OR between the LNU and ONU approaches for local recurrence did not differ markedly between the groups (OR 0.71, 95% CI 0.40–1.46, P= 0.25; Fig. 4). The pooled OR between the LNU and ONU approaches for distant metastasis favoured the LNU group (OR 0.72, 95% CI 0.54–0.97, P= 0.03; Fig. 5).

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Figure 3. Meta-analysis of observational studies reporting on lower urinary tract recurrence.

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Figure 4. Meta-analysis of observational studies reporting on local recurrence.

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Figure 5. Meta-analysis of observational studies reporting on distant metastasis.

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SURVIVAL RATES

In all, 17 observational studies reported survival rates [2,3,10–12,14,15,17–24,34,36] (Table 3). All studies consistently reported comparable oncological safety between LNU and ONU. The range of 5-year CSS for LNU and ONU was 95.2–71% and 92.6–63.5%, respectively. The range of 5-year RFS for LNU and ONU was 90.47–52.5% and 88.8–50.7%, respectively. The longest follow-up was reported by Stewart et al. [23] with a median of 163 months, reporting comparable oncological outcomes for 5-, 10-, and 15-year OS, PFS and CSS for the two approaches. Three retrospective multicentre studies [19,22,24] were identified. Capitanio et al. [19] reported oncological outcomes comparing LNU and ONU in 1249 patients. The 5-year RFS estimates were 86.8% and 76.2% for LNU and ONU, respectively. The 5-year cancer-specific-mortality-free survival estimates were 85.8% and 73.1% for LNU and ONU, respectively. Walton et al. [24] reported on a cohort of 773 patients. The estimated 5-year RFS was 63.4% and 73.7% for LNU and ONU, respectively (P= 0.124). The estimated 5-year CSS were 75.2% and 75.4% for the LNU and ONU groups, respectively (P= 0.897). Ariane et al. [22] reported oncological outcomes in 609 patients. The 5-year RFS was 52.2% and 50.7.7% for LNU and ONU, respectively (P= 0.7). The 5-year CSS were 90.7% and 78% for the LNU and ONU, respectively (P= 0.06). All the three studies on a multivariate analysis showed that the surgical approach (ONU or LNU) used did not influence the oncological outcomes.

Table 3. Survival rates for LNU vs ONU
StudyFollow-up, monthsSurvival rates, %
  1. ES, estimated survival.

Shalhav et al. 2000 [3]Mean 24Crude survival 77 vs 69
CSS 77 vs 77
Gill et al. 2000 [2]Mean LNU 11.1, ONU 34.4Crude survival 97 vs 94 (P= 0.59)
CSS 97 vs 87 (P= 0.59)
Rassweiler et al. 2004 [11]602-yearr survival 89 vs 83
5-year survival 81 vs 63
Bariol et al. 2004 [36]Median LNU 101, ONU 961-year metastasis-free survival rate 80 vs 87.2 (P= 0.33)
5-year metastasis-free survival rates 72 vs 82.1 (P= 0.26)
OS 56 vs 59 (P= 0.26) at median follow-up of 7 years
CSS 72 vs 82 (P= 0.516) at median follow-up of 7 years
Hattori et al. 2006 [12]Median ONU 35, LNU + open lower ureter 31, LNU + laparoscopic lower ureter 171-year CSS 95 vs 93 vs 93 (P= 0.89)
3-year CSS 81 vs 86 vs 80
5-year CSS 78 vs 81
1-year estimated extravesical RFS 77 vs 80 vs 89 (P= 0.91)
3-year estimated extravesical RFS 71 vs 76 vs 71
5-year estimated extravesical RFS 71 vs 71
1-year estimated bladder RFS 65 vs 78 vs 72 (P= 0.38)
3-year estimated bladder RFS 51 vs 65 vs 45
5-year estimated bladder RFS 51 vs 56
Rouprêt et al. 2007 [14]Median LNU 68.5, ONU 785-year CSS 90 vs 61.5 (P= 0.31)
5-year tumour-free survival rate 71.6 vs 51.2 (P= 0.59)
Manabe et al. 2007 [15]Median LNU 13.6, ONU 282-year disease-free survival rate 75.6 vs 81.7
2-year CSS 85.2 vs 87.0
2-year OS 83.7 vs 83.6
Hsueh et al. 2007 [10]Mean5-year CSS pT1 92 vs 88.1 (P= 0.745)
LNU 37.62-year overall recurrence rate 23 vs 27 (P= 0.95)
ONU 53.6
Taweemonkongsap et al. 2008 [17]Mean LNU 26.4, ONU 27.92-year CSS 86.3 vs 92.5 (P= 0.823)
2-year OS 86.3 vs 83.3 (P= 0.863)
Hemal et al. 2008 [16]Median LNU 53, ONU 575-year RFS 90.47 vs 88.8 (P= 1.0)
5-year CSS 95.2 vs 92.6 (P= 1.0)
5-year OS 85.7 vs 85.2 (P= 1.0)
Waldert et al. 2009 [18]Mean LNU 41, ONU 415 year CSS 85 vs 80 (P= 0.62) (ES)
5-year tumour free-survival rate 79 vs 76 (P= 0.82) (ES)
Capitanio et al. 2009 [19]Median 495-year RFS 86.8 vs 76.2
5-year CSS 85.8 vs 73.1
Greco et al. 2009 [20]Median 605-year disease-free survival 75 vs73 (P= 0.037)
Favaretto et al. 2010 [21]Median 232-year RFS 42 vs 38 (P= 0.9)
2-year CSS 82 vs 86 (P= 0.9)
Stewart et al. 2011 [23]Median 1635-year OS 61 vs 64
5-year PFS 76 vs 79
5-year CSS 71 vs 80
10-year OS 56 vs 48
10-year PFS 76 vs 79
10-year CSS 71 vs 80
15-year OS 11 vs 34
15-year PFS 76 vs 79
15-year CSS 64 vs 74
Ariane et al. 2011 [22]Median 275-year RFS 52.2 vs 50.7 (P= 0.7)
5-year CSS 90.7 vs 78 (P= 0.06)
Walton et al. 2011 [24]Median 345-year RFS 63.4 vs 73.3 (P= 0.124)
5-year CSS 75.2 vs 75.4 (P= 0.897)

OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

Three studies [30–32] compared NSS and radical NU (Table 4). Giannarini et al. [32] compared outcomes of 43 patients who underwent either distal ureter resection with bladder cuff excision and ureter re-implantation (19 patients) or radical NU for distal ureteric tumours (24). The 5- and 10-year bladder cancer-free survival (log-rank test, P= 0.117), OS (log-rank test, P= 0.693), and CSS (log-rank test, P= 0.896) were similar for the two groups. Hence, the study suggested distal ureterectomy as an option in distal ureteric tumours. Dragicevic et al. [30] and Lucas et al. [31] both compared conservative approaches with radical NU and reported equivalent oncological outcomes between the two groups in selected cases.

Table 4. Studies comparing outcomes of NSS and radical NU
StudyObjectivesFindings and survival rates, %
  1. HR, hazard ratio.

Giannarini et al. 2007 [32]Distal ureter resection with bladder cuff excision and ureter re-implantation vs radical NU with bladder cuff excisionCSS at 5 and 10 years was not statistically significantly different (log-rank test, P= 0.896)
OS at 5 and 10 years was not statistically significantly different (log-rank test, P= 0.693)
Dragicevic et al. 2009 [30]Open conservative surgery vs radical NU5-year survival rates 59 vs 55.
5-year survival rates for imperative and elective indications 41 vs 75.
Radical NU had statistically significantly poorer outcomes for the disease on univariate analysis (HR 2.2, 95% CI 1.1–4.6; P= 0.030)
Lucas et al. 2008 [31]NSS vs radical NULow-grade disease:
5-year OS 75.4 vs 66.4 (P= 0.281)
5-year CSS 86.2 vs 87.4 (P= 0.909)
High-grade disease:
5-year OS 45 vs 71.5 (P= 0.077)
5-year CSS 68.6 vs 75 (P= 0.528)

OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

One retrospective study was identified comparing ONU with a percutaneous approach [33]. This study showed the CSS rates after radical ONU and percutaneous NU for grade 2 disease were 53.8 and 53.3 months, respectively (P > 0.05), and concluded that the percutaneous NU should be an option in patients with solitary kidneys, those at risk of chronic renal failure, and healthy individuals with normal contralateral kidneys who are willing to comply with a strict and lengthy follow-up protocol.

OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

There were five retrospective studies identified in our search that compared various techniques of en bloc excision of the lower ureter [25–29] (Table 5). Bladder recurrence was reported by all the studies and ranged between 13.9% and 54.4% depending on the technique used. Other oncological outcomes reported were local recurrence, retroperitoneal and distant metastasis, recurrence and CSS. However, none of the studies reported statistically significant advantage of one technique over the other.

Table 5. Studies comparing the various techniques of en bloc excision of the lower ureter during the NU procedure
StudyObjectivesFindings with recurrence and metastasis rates, %
Romero et al. 2007 [25]Extravesical laparoscopic control of the bladder cuff vs extravesical open control of the bladder cuffOverall recurrence rates 66.7 vs 33.3 (P= 0.09).
Local recurrence rates16.7 vs 0 (P= 0.239).
Bladder recurrence rates 50 vs 33.3 (P= 0.233).
Distant metastasis 25 vs 8.3 (P= 0.248).
Ko et al. 2007 [28]Open excision of a bladder cuff (OC) vs transurethral incision of the ureteric orifice (TUIUO)The bladder recurrence rates were similar in the OC group (22.2; 6/27) and the TUIUO group (26.3; 5/19).
There were no pelvic recurrences in either group.
Salvador-Bayarri et al. 2002 [26]Open excision of a bladder cuff vs endoscopic resection of ureterBladder tumour recurrence 39 vs 34.5 (no statistical significance).
Matin et al. 2005 [29]Extravesical laparoscopic control of the bladder cuff vs cystoscopic secured detachment and ligation methodBladder tumour recurrence 41.7 vs 13.9 (not statistically significant).
Retroperitoneal metastasis 8.3 vs 5.6 (not statistically significant).
Distant metastasis 25 vs 8.3 (not statistically significant).
Walton et al. 2009 [27]Endoscopic ureteric detachment vs open bladder cuff excisionBladder tumour recurrence 54.4 vs 47.9 (not statistically significant).
RFS and CSS similar for both groups

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

The search strategy for this review included a comprehensive search of electronic databases, meticulous hand searching of relevant journal articles and abstracts. Despite laparoscopic and minimally invasive approaches being common place in contemporary urological practice for more than two decades, there is a paucity of good quality RCTs comparing surgical techniques (one RCT in 400 publications; 0.25%). Apart from this RCT, current evidence to guide surgical practice is based on a large number of retrospective observational studies. The reported data suggests significantly better perioperative outcomes with laparoscopic and minimally invasive approaches with equivalent long-term oncological control of the disease. A meta-analysis of the observational studies comparing LNU and ONU reporting on bladder recurrence and distant metastasis favoured the laparoscopic group. However, we would strongly recommend caution in interpreting these results, given the various methodological problems with the retrospective study design, particularly the selection biases, small sample sizes and lack of statistical power. Indeed the OS, CSS, RFS after adjustment for confounding factors, particularly stage and grade, show consistent oncological equivalence between the two approaches in all the studies. All the studies reporting on immediate outcomes consistently show laparoscopic superiority for reduced intraoperative blood loss and hospital stay. Operative durations tended to be longer in the laparoscopic group. There continues to be lack of clarity about the best approach to deal with the lower end of the ureter. There has been some suggestion of a high risk of progression with the ‘pluck’ techniques, although this risk is not clearly established. The five studies identified in this review did not show a particular approach to be better and current practice remains an issue of surgeon's preference and experience [25–29]. With evolving minimally invasive approaches in the surgical management of UUT-TCC, NSS is a further extension. The early evidence would suggest that these approaches may have similar oncological outcomes in comparisons with radical NU for organ-confined disease, particularly for low-grade small tumours.

This review reflects that urological surgeons over the years have accepted the results of weaker clinical studies with retrospective designs and selection bias for the surgical management of UUT-TCC. Surgical technology appears to have disseminated rapidly in surgical practice without good scrutiny for assessing its clinical effectiveness. There are several established issues in conducting a well-designed RCT in surgery. Patient choice remains the most important and perhaps poorly understood factor in performing a RCT. Elective participation by an individual in a RCT is dependent on the information presented in an unbiased way. In addition, surgeons may have personal preference for certain techniques, which may reflect their own previous training and expertise [37]. With the introduction of robotic technology, a trial assessing robot-assisted LNU vs conventional LNU would be an ideal beginning. Considering the challenges associated with performing a RCT in surgical practice it has been suggested that progressive surgical research will have to be reliant on good quality non-randomised trials.

CONCLUSIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

There has been a paradigm shift over the years in the surgical management of UUT-TCC, with LNU being the standard of care in most institutions. However, there is a paucity of good quality evidence for the various surgical approaches for UUT-TCC. The techniques have been assessed and reported in many retrospective single-centre studies favouring the laparoscopic approach for better perioperative outcomes and comparable oncological safety. The reported observational studies data are further supported by one RCT.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES

Tayside Endowment funds.

This systematic review was conducted under the aegis of the Cochrane collaboration and published on the Cochrane library in 2011, issue 4. The present version has been extended to include data from observational studies.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. RCT OF LNU VS ONU
  7. OBSERVATIONAL STUDIES COMPARING LNU VS ONU
  8. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS NSS
  9. OBSERVATIONAL STUDIES COMPARING RADICAL NU VS PERCUTANEOUS NU
  10. OBSERVATIONAL STUDIES COMPARING VARIOUS TECHNIQUES FOR DEALING WITH THE LOWER END OF THE URETER
  11. DISCUSSION
  12. CONCLUSIONS
  13. ACKNOWLEDGEMENTS
  14. CONFLICT OF INTEREST
  15. REFERENCES
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