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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

Read the full article
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.

Read more articles of the week

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

 

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

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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

Read the full article
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.

Read more articles of the week

Article of the week: Nephron-sparing management vs radical nephroureterectomy

/by

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 prominent members 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 Dr. Jay Simhan dicsussing his paper.

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

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

Jay Simhan, Marc C. Smaldone, Brian L. Egleston*, Daniel Canter†, Steven N. Sterious, Anthony T. Corcoran, Serge Ginzburg, Robert G. Uzzo and Alexander Kutikov

Division of Urologic Oncology, Departments of Surgical Oncology, *Biostatistics, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA and †Department of Urology, Emory University School of Medicine, Atlanta, GA, USA

Read the full article
OBJECTIVE

• To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset.

PATIENTS AND METHODS

• Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy).

• Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively.

RESULTS

• Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008.

• Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001).

• While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26).

CONCLUSIONS

• Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU.

• These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Read more articles of the week

Editorial: Upper tract urothelial carcinoma: do we really need to burn down the house?

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In this issue, Simhan et al. [1] use the Surveillance, Epidemiology, and End Results (SEER) database to compare outcomes of nephron-sparing and radical extirpative therapy for upper tract urothelial carcinoma (UTUC). Their study sheds some well-needed light on a difficult clinical dilemma.

A diagnosis of low- or moderate-grade, low-stage UTUC is akin to finding a spot of suspicious green mould on your attic drywall. The scale and potential danger of the problem may not be immediately apparent and both patient and urologist must make tough choices with incomplete information. Spot treat the problem and preserve nephrons via endoscopic or segmental resection or burn down the house with radical nephroureterectomy to minimise recurrence and progression risk? With only relatively small datasets for guidance and the uncertainty of endoscopic biopsy, many urologists have a low threshold to proceed with radical therapy, perhaps unnecessarily.

Simhan et al. [1] identified 1227 patients in the SEER dataset with low- or moderate-grade, localised, non-invasive UTUC who were treated either with nephron-sparing procedures (endoscopic resection or segmental ureterectomy) or nephroureterectomy between 1992 and 2008. For this cohort, radical therapy with nephroureterectomy imparted no advantage in cancer-specific survival. Patients undergoing nephron sparing were slightly older and did experience higher non-cancer specific mortality. This may reflect an underlying bias to offer nephron sparing to older patients with a greater burden of comorbidities and shorter life expectancy. These results corroborate another large SEER study from 2010, which documented no difference in cancer-specific mortality when comparing segmental resection with nephroureterectomy for T1–T4 N0M0 urothelial carcinoma of the ureter [2].

Population-based tumour registry studies are complementary to institutional series and are particularly valuable for rare tumours like UTUC. However, they have their limitations and these are outlined clearly in the Simhan et al. [1] article. Most notable are the lack of linked comorbidity information and the inability to separate segmental resection from endoscopic management in the nephron-sparing group. We should avoid the temptation to broaden indications for endoscopic resection to all patients with low-grade, low-stage UTUC of the renal pelvis and calyces. After all, the authors present no data on: (i) local recurrence and reoperation rates, (ii) progression to radical nephroureterectomy or (iii) correlation between endoscopic biopsy results and the ultimate pathology from nephroureterectomy specimens.

Over the past decade, there has been a progressive movement toward nephron-sparing approaches for treatment of T1 RCC, even in the context of a normal contralateral kidney. This transition has been fuelled by data showing the substantial negative impact of chronic kidney disease (CKD) on cardiovascular events and overall mortality [3]. Broader application of this philosophy to the treatment of low- or moderate-grade, low-stage UTUC would be a natural next step. This is particularly true given the advantage of maximising nephrons should disease progression necessitate platinum-based chemotherapy.

However, endoscopic resection of UTUC carries a much higher burden of local recurrence (20–85%) [4], than does partial nephrectomy for RCC. Patients with UTUC often require multiple serial endoscopic resections and years of complicated and costly surveillance. More recent data also suggests that surgically induced CKD may not carry the same risk of progression and mortality as medical CKD [5]. Perhaps burning down the house is not as potentially destructive as we once thought?

With these caveats firmly in mind, the Simhan et al. [1] study does support a growing appreciation that nephron-sparing approaches to low- or moderate-grade, low-stage UTUC do not worsen cancer-specific mortality. Although these findings are encouraging, I agree with the authors that patient selection for nephron sparing should continue to be informed by clinical judgment and adherence to published treatment guidelines [6].

Richard E. Link
Associate Professor of Urology, Director, Division of Endourology and Minimally Invasive Surgery, Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

References

  2. Jeldres C, Lughezzani G, Sun M et al. Segmental ureterectomy can safely be performed in patients with transitional cell carcinoma of the ureter. J Urol 2010; 183: 1324–1329
  3. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305
  4. Bagley DH, Grasso M 3rd. Ureteroscopic laser treatment of upper urinary tract neoplasms. World J Urol 2010; 28: 143–149
  5. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013; 189: 1649–1655
  6. Roupret M, Zigeuner R, Palou J et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 2011; 59: 584–594

 

Video: Nephron sparing vs radical nephroureterectomy for UTUC

/by

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

Jay Simhan, Marc C. Smaldone, Brian L. Egleston*, Daniel Canter†, Steven N. Sterious, Anthony T. Corcoran, Serge Ginzburg, Robert G. Uzzo and Alexander Kutikov

Division of Urologic Oncology, Departments of Surgical Oncology, *Biostatistics, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA and †Department of Urology, Emory University School of Medicine, Atlanta, GA, USA

Read the full article
OBJECTIVE

• To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset.

PATIENTS AND METHODS

• Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy).

• Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively.

RESULTS

• Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008.

• Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001).

• While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26).

CONCLUSIONS

• Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU.

• These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Read more articles of the week
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