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Article of the Month: An analysis of robot-assisted vs conventional pyeloplasty in children

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Meta-analysis of robot-assisted vs conventional laparoscopic and open pyeloplasty in children

Thomas P. Cundy*, Leanne Harling†, Archie Hughes-Hallett*†, Erik K. Mayer†, Azad S. Najmaldin‡, Thanos Athanasiou†, Guang-Zhong Yang* and Ara Darzi*†

*The Hamlyn Centre, Institute of Global Health Innovation, and †Department of Surgery and Cancer, St Mary’s Hospital, Imperial College, London; and ‡Department of Paediatric Surgery, Leeds General Infirmary, Leeds, UK

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OBJECTIVE

To critically analyse outcomes for robot-assisted pyeloplasty (RAP) vs conventional laparoscopic pyeloplasty (LP) or open pyeloplasty (OP) by systematic review and meta-analysis of published data.

PATIENTS AND METHODS

Studies published up to December 2013 were identified from multiple literature databases. Only comparative studies investigating RAP vs LP or OP in children were included. Meta-analysis was performed using random-effects modelling. Heterogeneity, subgroup analysis, and quality scoring were assessed. Effect sizes were estimated by pooled odds ratios and weighted mean differences. Primary outcomes investigated were operative success, re-operation, conversions, postoperative complications, and urinary leakage. Secondary outcome measures were estimated blood loss (EBL), length of hospital stay (LOS), operating time (OT), analgesia requirement, and cost.

RESULTS

In all, 12 observational studies met inclusion criteria, reporting outcomes of 384 RAP, 131 LP, and 164 OP procedures. No randomised controlled trials were identified. Pooled analyses determined no significant differences between RAP and LP or OP for all primary outcomes. Significant differences in favour of RAP were found for LOS (vs LP and OP). Borderline significant differences in favour of RAP were found for EBL (vs OP). OT was significantly longer for RAP vs OP. Limited evidence indicates lower opiate analgesia requirement for RAP (vs LP and OP), higher total costs for RAP vs OP, and comparable costs for RAP vs LP.

CONCLUSIONS

Existing evidence shows largely comparable outcomes amongst surgical techniques available to treat pelvi-ureteric junction obstruction in children. RAP may offer shortened LOS, lower analgesia requirement (vs LP and OP), and lower EBL (vs OP); but compared with OP, these gains are at the expense of higher cost and longer OT. Higher quality evidence from prospective observational studies and clinical trials is required, as well as further cost-effectiveness analyses. Not all perceived benefits of RAP are easily amenable to quantitative assessment.

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Editorial: Robot-assisted pyeloplasty in children

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The authors of the study on robot-assisted pyeloplasty in this issue of BJUI have carried out an excellent review of the current data on this common paediatric urology procedure [1]. Although the analysis involves small case numbers and series for meta-analysis, the data are useful for current practice. It may be worth waiting another 5 years to review the data again, by which time the learning curve for most of the surgeons will be over, and a true representation of practice and a comparison against the established standard open surgery, which has been established over decades, can be reported. The training of next-generation surgeons needs to be factored into this process, which is critically important.

With the different methods of critical evaluation presently available, we may be able to draw some conclusions from the results of robot-assisted pyeloplasty, but the problem that remains is the inconsistency of individual reports in terms of outcome and complications. We surgeons need to work on developing a consensus model for the evaluation of each procedure so that uniformity exists. The financial implications of new technology will always be higher than expected, but with a greater number of users and competitive producers the cost will be remarkably reduced. As paediatric surgeons, we do not know the unseen benefits of robot-assisted pyeloplasty, but the children’s families have a positive perception of post-surgical aesthetic appearance, and may also have some human capital gains in terms of reduced childcare expenditure. The paradigm shift to a digital era of surgery is here to stay, with safety and refinements to technology being universally available to all children.

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Mohan S. Gundeti

BJUI Consulting Editor, Paediatrics, The Medicine University of Chicago, Chicago, IL, USA

References

1. Cundy TP, Harling L, Hughes-Hallett A et al. Meta analysis of robot-assisted vs conventional laparoscopic and open pyeloplasty in children. BJU Int 2014; 114: 582–94

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Article of the Week: Centralized histopathological review in penile cancer. Should this be the global standard?

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Should centralized histopathological review in penile cancer be the global standard?

Vincent Tang, Laurence Clarke, Zara Gall, Jonathan H. Shanks, Daisuke, Nonaka, Nigel J. Parr, P. Anthony Elliott, Noel W. Clarke, Vijay Ramani, Maurice W. Lau and Vijay K. Sangar

The Christie NHS Foundation Trust, Manchester and the *Royal Bolton NHS Foundation Trust, Bolton, UK

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OBJECTIVE
  • To assess the role of centralized pathological review in penile cancer management.
MATERIALS AND METHODS
  • Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011.
  • Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists.
  • The biopsy specimens’ histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology.
  • Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management).
RESULTS
  • A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England.
  • After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management.
  • When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found.
CONCLUSIONS
  • In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management.
  • The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer.
  • In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the ‘gold standard’.
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Editorial: A call for the international adoption of penile specialist networks

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The recent article by Tang et al. [1] from the Christie Hospital in Manchester raises an interesting question. The urological cancer plan for England and Wales specifies that review of the pathology of prostate and high-risk superficial bladder cancer should take place as part of the referral process for these cases to specialist pelvic cancer teams, but the penile pathway does not indicate that this is necessary [2]. The Royal College of Pathologists [3] also specifies the need for expert review and/or double reporting in other rare cancers and dysplasias, but does not yet specify this for penile cancers.

Penile cancers are rare, with 600 new cases diagnosed in the UK per year. They are almost invariably squamous cell carcinomas, which also occur at other sites including the lung, upper aerodigestive tract and skin. This may lead some pathologists to assume that they are similar and do not need second opinion or review; however, the subtypes of squamous cell carcinoma that occur on the penis are not common elsewhere, include basaloid, warty and verrucous carcinomas [4], and are not always recognized by general pathologists. The anatomy of the penis is challenging and the identification of invasion of urethra, corpus spongiosum and corpus cavernosum is important in accurate staging. Penile cancers have their own TNM system. TNM7, published in 2010 [5], recognises the importance of grading and different stage groups on prognosis.

Our own experience at St George’s Hospital in South London mirrors that of the Christie Hospital in North West England. Our practice from the outset of the establishment of our supra-regional penile centre was to review outside pathology in the setting of our specialist multidisciplinary meeting to devise a management plan for each patient. We also found that our reviewed cases were more likely to be under-graded and that staging was frequently inaccurate if it was attempted at all. Our original audit was presented at the BAUS annual meeting in 2005. We repeated the audit in 2008 after the publication of the Royal College of Pathologists guidelines on the reporting of penile cancer and found no improvement (unpublished data).

An average urological pathologist in a non-specialist centre in the UK will only see 1–3 cases of penile cancer per year and will have little opportunity or incentive to gain expertise in this area. Although second opinion services through the supra-networks are freely available, these are not always sought, perhaps because of time pressures and the mistaken impression that penile cancers are like those of other sites. There is also a lack of awareness of new entities, for example, differentiated penile intraepithelial neoplasia (PeIN) and subtypes of undifferentiated PeIN. There has been a recent change in nomenclature, whereby all morphological types of squamous carcinoma in situ and dysplasias are now classified within PeIN [6].

The supra-network of penile centres in the UK has allowed a small group of pathologists to gain expertise in the reporting of penile cancer in a specialist clinical setting, and has produced a group of pathologists with a special interest in this type of tumour, all of whom are seeing at least 25 new cases per year. Many centres are seeing more, with our own centre managing 126 new cases in 2012.

In 2008 we formed a UK-wide group of specialist penile pathologists (the Hobnobs) which meets annually to exchange both clinical and research information and to discuss individual cases. Members of this group are currently updating the Royal College of Pathologists penile guidelines [3]. These will advise central review, but we recognize we are writing them mainly for specialist pathologists to ensure consistent and high-quality assessment of penile cancer to inform the penile cancer team.

In the UK, expert pathological review of penile cancer is already the norm for the penile supra-networks, but it would be difficult to make this the global standard for several reasons. Sub-specialization in penile cancer management is not widely practised outside Britain and there are few specialist high-volume centres, with some notable exceptions in Europe and the USA. Without clinical sub-specialization it is difficult for pathologists to develop an interest and sufficient expertise to offer an expert second opinion because the numbers seen by any individual pathologist will be too small.

The UK penile supra-network system works well and has led to a group of pathologists developing an interest in this area simply because they are seeing a large number of such cases and working with dedicated clinical teams. Penile supra-networks should be adopted worldwide. Following this, a group of expert and experienced pathologists will ultimately be developed, who can offer a central review and expert second opinion service, as has happened over the last 10 years in the UK.

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Catherine M. Corbishley
Department of Cellular Pathology, St George’s Healthcare NHS
Trust, London, UK

References

1. Tang V, Clarke L, Gall Z et al. Should centralised histopathological review in penile cancer be the global standard? BJU Int 2014;114: 340–343

2. Manual for Cancer services. Urology measures Version 2.1. NHS National Cancer Peer Review Programme 2011 and Evidence guide for Urology Supraregional Penile MDT NHS National Cancer Peer Review Programme 2010.

3. Royal College of Pathologists. Cancer Datasets and Tissue Pathways. Available at: https://www.rcpath.org/publications-media/publications/datasets.

4. Epstein JI, Cubilla AL, Humphrey PA. Tumours of the Prostate Gland, Seminal Vesicles, Penis and Scrotum. American Registry of Pathology, Washington DC published in collaboration with the Armed Forces Institute of Pathology, 2011, 405–612

5. Gospodarowicz MK (section editor, Genitourinary Tumours). TNM classification of malignant tumours (7th edition) penis. In Edge SB,Byrd DR, Compton CC Fritz AG, Greene FL, Trotti A eds, AJCC Cancer Staging Manual, 7th edn. New York: Springer, 2010:447–455

6. Velazquez EF, Chaux A, Cubilla AL. Histologic classification of penile intraepithelial neoplasia. Semin Diagn Pathol 2012; 29: 96–102

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Article of the week: RP is safe in patients taking aspirin

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Mr. Sami-Ramzi Leyh-Bannurah discussing his paper.

If you only have time to read one article this week, it should be this one.

Open and robot-assisted radical retropubic prostatectomy in men receiving ongoing low-dose aspirin medication: revisiting an old paradigm?

Sami-Ramzi Leyh-Bannurah, Jens Hansen, Hendrik Isbarn, Thomas Steuber, Pierre Tennstedt, Uwe Michl, Thorsten Schlomm*, Alexander Haese, Hans Heinzer, Hartwig Huland, Markus Graefen and Lars Budäus

Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, and *Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Read the full article
OBJECTIVE

• To assess blood loss, transfusion rates and 90-day complication rates in patients receiving ongoing 100 mg/day aspirin medication and undergoing open radical prostatectomy (RP) or robot-assisted RP (RARP).

PATIENTS AND METHODS

• Between February 2010 and August 2011, 2061 open RPs and 400 RARPs were performed. All patients received low-molecular-weight heparin for thrombembolism prophylaxis. Aspirin intake during surgery was recorded in 137 patients (5.5%).

• Descriptive statistics and multivariable analyses after propensity-score matching for balancing potential differences in patients with and without aspirin medication were used to assess the risk of blood loss above the median in patients undergoing open RP or RARP.

RESULTS

• The median blood loss in the open RP cohort with and without aspirin medication was 750 and 700 mL, respectively, and in the RARP cohort it was 200 and 150 mL, respectively. Within the same cohorts, transfusions were administered in 21 and 8% and 0 and 1% of patients, respectively.

• The 90-day complication rates in patients with ongoing aspirin medication were 5.8, 4.4, 7.3 and 0% for Clavien grades I, II, III and IV complications, respectively.

• In multivariable analyses and after propensity-score matching, prostate volume (odds ratio 1.03; 95% CI 1.02–1.04; P < 0.01) but not ongoing aspirin medication achieved independent predictor status for the risk of blood loss above the median.

CONCLUSIONS

• Major surgery such as open RP and RARP can be safely performed in patients with ongoing aspirin medication without greater blood loss.

• Higher 90-day complication rates were not detected in such patients.

• Differences in transfusion rates between the groups receiving and not receiving ongoing aspirin medication may be explained by a higher proportion of patients with coronary artery disease in the group receiving ongoing aspirin mediciation. This comorbidity may result in a higher peri-operative threshold for allogenic blood transfusion.

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Editorial: Perioperative aspirin: To give or not to give?

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As the population ages and life expectancy increases, one may safely assume that more men will be diagnosed with diseases of the elderly such as prostate cancer. In the USA, it is estimated that the number of older adults (≥65 years old) will double between 2010 and 2030, contributing to a 45% increase in cancer incidence [1]. Also, it is likely that these older patients will present with multiple comorbidities, commonly described as ‘multimorbidity’ in the contemporary medical literature, including chronic cardiac and pulmonary conditions requiring multidisciplinary medical management.

Hence, the present study by Leyh-Bannurah et al. [2] examining the peri-operative use of aspirin in patients undergoing radical prostatectomy (RP) is a timely and important contribution, and may very well influence our clinical decision-making regarding the perioperative management of the anti-coagulated patient. Their results show that perioperative continuation of aspirin made no difference in peri and postoperative outcomes following RP. Previous studies have assessed the effect of aspirin continuation in patients undergoing minimally invasive RP, but the present study is the first to evaluate the effect of aspirin continuation in patients undergoing minimally invasive and open RP at a high-volume tertiary centre. Studies from other surgical specialties evaluating the role of anti-platelet therapy and its timing before surgery have shown conflicting results. The study by Park et al. [3], looking at discontinuation of aspirin for ≥7 days vs <7 days before surgery in patients undergoing lumbar spinal fusion, found that aspirin discontinued only 3–7 days before surgery significantly increased the risk of intraoperative bleeding. Alghamdi et al. [4] found similar results in patients undergoing coronary artery bypass grafting. In contrast, the study by Wolf et al. [5] showed that continuation of aspirin up to the day of the surgery did not increase the risk of bleeding, transfusion or other adverse outcomes in patients undergoing pancreatectomy. Similarly, Khudairy et al. [6] assessed the use of clopidogrel and its discontinuation time in hip fracture repair, and found that whether it was stopped ≥1 week or <1 week before surgery did not make any difference to the risk of bleeding or peri-operative complications. Nonetheless, the evidence provided by the present study by Leyh-Bannurah et al. is important, as the risk of bleeding seems to be procedure-specific, depending on the nature and source of potential bleeding (primarily arterial vs primarily venous). The lack of information, however, regarding cardiovascular morbidities in their patient population is an important limitation of their study; as such factors may influence perioperative decision-making, including the threshold for transfusion.

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Akshay Sood and Quoc-Dien Trinh*
VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

References

  1. Lamb A. Fast Facts: prostate cancer, seventh edition. BJU Int 2012; 110: E157
  3. Park JH, Ahn Y, Choi BS et al. Antithrombotic effects of aspirin on 1- or 2-level lumbar spinal fusion surgery: a comparison between 2 groups discontinuing aspirin use before and after 7 days prior to surgery. Spine 2013; 38: 1561–1565
  4. Alghamdi AA, Moussa F, Fremes SE. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J Cardiac Surg 2007; 22: 247–256
  5. Wolf AM, Pucci MJ, Gabale SD et al. Safety of perioperative aspirin therapy in pancreatic operations. Surgery 2014; 155: 39–46
  6. Al Khudairy A, Al-Hadeedi O, Sayana MK, Galvin R, Quinlan JF. Withholding clopidogrel for 3 to 6 versus 7 days or more before surgery in hip fracture patients. J Orthop Surg 2013; 21: 146–150
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Video: Effect of peri-operative aspirin medication in open or robot-assisted RP

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Open and robot-assisted radical retropubic prostatectomy in men receiving ongoing low-dose aspirin medication: revisiting an old paradigm?

Sami-Ramzi Leyh-Bannurah, Jens Hansen, Hendrik Isbarn, Thomas Steuber, Pierre Tennstedt, Uwe Michl, Thorsten Schlomm*, Alexander Haese, Hans Heinzer, Hartwig Huland, Markus Graefen and Lars Budäus

Martini Clinic, Prostate Cancer Center at University Hospital Hamburg-Eppendorf, and *Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Read the full article
OBJECTIVE

• To assess blood loss, transfusion rates and 90-day complication rates in patients receiving ongoing 100 mg/day aspirin medication and undergoing open radical prostatectomy (RP) or robot-assisted RP (RARP).

PATIENTS AND METHODS

• Between February 2010 and August 2011, 2061 open RPs and 400 RARPs were performed. All patients received low-molecular-weight heparin for thrombembolism prophylaxis. Aspirin intake during surgery was recorded in 137 patients (5.5%).

• Descriptive statistics and multivariable analyses after propensity-score matching for balancing potential differences in patients with and without aspirin medication were used to assess the risk of blood loss above the median in patients undergoing open RP or RARP.

RESULTS

• The median blood loss in the open RP cohort with and without aspirin medication was 750 and 700 mL, respectively, and in the RARP cohort it was 200 and 150 mL, respectively. Within the same cohorts, transfusions were administered in 21 and 8% and 0 and 1% of patients, respectively.

• The 90-day complication rates in patients with ongoing aspirin medication were 5.8, 4.4, 7.3 and 0% for Clavien grades I, II, III and IV complications, respectively.

• In multivariable analyses and after propensity-score matching, prostate volume (odds ratio 1.03; 95% CI 1.02–1.04; P < 0.01) but not ongoing aspirin medication achieved independent predictor status for the risk of blood loss above the median.

CONCLUSIONS

• Major surgery such as open RP and RARP can be safely performed in patients with ongoing aspirin medication without greater blood loss.

• Higher 90-day complication rates were not detected in such patients.

• Differences in transfusion rates between the groups receiving and not receiving ongoing aspirin medication may be explained by a higher proportion of patients with coronary artery disease in the group receiving ongoing aspirin mediciation. This comorbidity may result in a higher peri-operative threshold for allogenic blood transfusion.

Read more articles of the week

Article of the week: Guideline of guidelines: prostate cancer screening

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The introduction is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

If you only have time to read one article this week, it should be this one.

Guideline of guidelines: prostate cancer screening

Stacy Loeb
Department of Urology and Population Health, New York University, New York, NY, USA

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INTRODUCTION

Prostate cancer screening is one of the most controversial topics in urology [1]. On one hand, there is randomised data showing that PSA screening results in earlier stages at diagnosis, improved oncological outcomes after treatment, and lower prostate cancer mortality rates. However, the downsides include unnecessary biopsies due to false-positive PSA tests, over-diagnosis of some insignificant cancers, and potential side-effects from prostate biopsy and/or prostate cancer treatment. The ongoing controversy is highlighted by the divergent recommendations on screening from multiple professional organisations. The purpose of this article is to summarise the recent guidelines on prostate cancer screening from 2012 to present.

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Article of the Month: Neutrophil–lymphocyte ratio helps predict survival in patients with upper tract urothelial carcinoma

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Georg Hutterer discussing his paper.

If you only have time to read one article this week, it should be this one.

Validation of pretreatment neutrophil–lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma

Orietta Dalpiaz, Georg C. Ehrlich, Sebastian Mannweiler*, Jessica M. Martín Hernández, Armin Gerger†, Tatjana Stojakovic‡, Karl Pummer, Richard Zigeuner, Martin Pichler† and Georg C. Hutterer

Department of Urology, *Institute of Pathology, †Division of Oncology, Department of Internal Medicine, and ‡Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria

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OBJECTIVE

• To investigate the potential prognostic significance of the neutrophil–lymphocyte ratio (NLR) in a large European cohort of patients with upper urinary tract urothelial cell carcinoma (UUT-UCC).

PATIENTS AND METHODS

• We retrospectively evaluated data from 202 consecutive patients with non-metastatic upper urinary tract urothelial cell carcinoma (UUT-UCC), who underwent surgery between 1990 and 2012 at a single tertiary academic centre.

• Patients’ cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan–Meier method.

• To evaluate the independent prognostic significance of the NLR, multivariate proportional Cox regression models were applied for both endpoints.

RESULTS

• A higher NLR was significantly associated with shorter CSS (P = 0.002, log-rank test), as well as with shorter OS (P < 0.001, log-rank test).

• Multivariate analysis identified a high NLR as an independent prognostic factor for patients’ CSS (hazard ratio 2.72, 95% CI 1.25–5.93, P = 0.012), and OS (hazard ratio 2.48, 95% CI 1.31–4.70, P = 0.005).

CONCLUSIONS

• In the present cohort, patients with a high preoperative NLR had higher cancer-specific and overall mortality after radical surgery for UUT-UCC, compared with those with a low preoperative NLR.

• This easily identifiable laboratory measure should be considered as an additional prognostic factor in UUT-UCC in future.

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Editorial: Neutrophil-to-lymphocyte ratio as a prognostic factor in upper tract urothelial cancer

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The immune system response is critical to cancer development, treatment and progression. Dalpiaz et al. [1]. show that patients with a higher neutrophil-to-lymphocyte ratio (NLR) have a higher cancer-specific and overall mortality when undergoing radical nephroureterectomy for upper tract urothelial cell cancer (UTUC). The study is the first and largest one to evaluate the impact of preoperative NLR on UTUC and proposes its incorporation into our risk assessment tools as an independent predictor of survival.

Pathological prognostic factors such as tumour stage and grade have established importance in UTUC [2]. Additionally, lymphovascular invasion and tumour necrosis have been shown to be independent predictors of survival [3]. Preoperative markers have the advantage of prospective planning and counselling for treatment. The NLR has been studied in various cancers, including renal and gastric, and was recently incorporated into a risk stratification scheme for radical cystectomy patients as an independent prognostic factor for survival [4].

Dalpiaz et al. retrospectively reviewed 202 patients with UTUC who underwent radical nephroureterectomy. A threshold NLR value of 2.7 was used to discriminate between patients. NLR was significantly associated with lymphovascular invasion, but not with age, gender, tumour site, vascular invasion, tumour grade, pathological T-stage, tumour site, tumour location or presence of tumour necrosis. The mean follow-up was 45 months. The median survival was 44.5 months in the low-NLR group and 27 months in the high-NLR group. Multivariate analysis showed that T-stage and NLR were predictors of cancer-specific survival. High NLR and muscle invasion were shown to be independent predictors of overall survival.

Although interesting, these results should be interpreted cautiously as it is very difficult to control all confounders in a retrospective study. The authors did try to address aspects of the inflammatory response by incorporating Eastern Cooperative Oncology Group Performance Status and Charlson Comorbidity Index into their analysis. They found no statistically significant association between NLR and Eastern Cooperative Oncology Group Performance Status or Charlson Comorbidity Index. When adjusting for these variables, the relationships between NLR and cancer-specific survival and between NLR and overall survival were maintained. Although helpful in supporting the conclusions, using the Eastern Cooperative Oncology Group Performance Status and Charlson Comorbidity Index as markers of the inflammatory response should be approached carefully, as many other factors, such as hydronephrosis, tumour invasion, and pre-procedure treatments, which were not evaluated could have a more significant effect on the NLR than general measures of chronic conditions.

The threshold value of the NLR (2.7) was obtained by testing all possible thresholds and choosing a value based on its ability to predict survival and mathematical convenience. Thus the threshold value is self-serving to the conclusion. The statistical analysis suffers due to the dichotomous discrimination as opposed to further divisions like quartiles, but nonetheless shows the value of NLR as an important predictor, the threshold value of which might differ from cohort to cohort.

The present study shows that NLR as an important predictor of survival in UTUC. NLR is easy to perform, relatively inexpensive and is probably already available as part of the standard evaluation of patients with UTUC. It is therefore easy to assess. How should it change our practices? For example, should we be considering neoadjuvant chemotherapy, lymph node dissections or earlier radical surgery in patients with high NLR? The present study develops the hypothesis that can serve as the basis of future validation in a larger cohort or in a prospective fashion.

Read the full article

Moben Mirza
Department of Urology, University of Kansas, Kansas City, KS, USA

References
  2. Rouprêt M, Hupertan V, Seisen T et al.; French National Database on Upper Tract Tumors; Upper Tract Urothelial Carcinoma Collaboration. Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis. J Urol 2013; 189: 1662–1669
  3. Zigeuner R, Shariat SF, Margulis V et al. Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract. Eur Urol 2010; 57: 575
  4. Gondo T, Nakashima J, Ohno Y et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 2012; 79: 1085

 

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