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

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

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.

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

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.

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

References
  1. 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
  2. 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
  3. 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

 

Video: Prognostic value of neutrophil–lymphocyte ratio in patients with UTUC

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

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.

Guideline of Guidelines

Many of us have developed an addiction to sports this summer. The World Cup football in Brazil with its continuous party spirit, the lush green lawns of Wimbledon and then the Test series between India and England. Our Web Editor could not contain himself:

Amidst all the fun and excitement, three important pieces of news are highlighted here:
  1. I requested our Associate Editor Stacy Loeb, who has a strong background in statistical methodology and health services research, to launch a series entitled ‘Guideline of Guidelines’. Most busy urologists tell me that they often find the many different society guidelines confusing. So we decided to publish a critical summary, finishing up with a set of ‘key points’ that our readers can use in their day-to-day practices. And what better way to kick off than with our biggest controversy – screening for prostate cancer [1].
  1. At #BAUS14 we conducted a live audience poll on when (and if) we should go completely digital. Here are the results:
  1. Inflammatory responses to tumours are recognised as being as important as stage and grade in predicting outcomes of treatment. Our ‘Article of the Month’ is a large 12-year European series of radical surgery for upper tract TCC. Neutrophil–lymphocyte ratio appears to be an important biomarker, as values of >2.7 confer worse cancer-specific and overall survivals [2]. The ratio of total neutrophils:total lymphocytes is easy to calculate from a routine preoperative blood test. I hope that many of you will be able to counsel your patients with this clinically useful biomarker.

Prokar Dasgupta
Editor-in-Chief, BJUI
Guy’s Hospital, King’s College London, London, UK

References

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