Georg C. Hutterer

Validation of the pre-treatment neutrophil–lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients

Background:The neutrophil–lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Several studies suggest a negative impact of increased NLR for patient’s survival in different types of cancer. However, previous findings from small-scale studies revealed conflicting results about its prognostic significance with regard to different clinical end points in non-metastatic renal cell carcinoma (RCC) patients. Therefore, the aim of our study was the validation of the prognostic significance of NLR in a large cohort of RCC patients.Methods:Data from 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single centre, were evaluated retrospectively. Cancer-specific, metastasis-free, as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of NLR, multivariate Cox regression models were applied for all three different end points. Influence of the NLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrells concordance index.Results:Multivariate analysis identified increased NLR as an independent prognostic factor for overall (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.10–2.31, P=0.014), but not for cancer-specific (HR=1.59, 95% CI=0.84–2.99, P=0.148), nor for metastasis-free survival (HR=1.39, 95% CI=0.85–2.28, P=0.184). The estimated concordance index was 0.79 using the Leibovich risk score and 0.81 when NLR was added.Conclusion:Regarding patients’ OS, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. Adding the NLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.

C-reactive protein is an informative predictor of renal cell carcinoma-specific mortality: a European study of 313 patients.

C‐reactive protein (CRP) represents a promising prognostic variable in patients with sporadic renal cell carcinoma (RCC). It was hypothesized that CRP can improve the prognostic ability of standard RCC‐specific mortality (RCC‐SM) predictors in patients treated with nephrectomy for all stages of RCC.

Comparison of stage migration patterns between Europe and the USA: An analysis of 11 350 men treated with radical prostatectomy for prostate cancer

To examine the stage migration patterns in patients treated with radical prostatectomy (RP) for prostate cancer in Europe and in the USA in the last 20 years.

Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location

To better define the predictors of bladder tumour development in patients operated for upper urinary tract urothelial cancer (UT‐UC).

External validation of the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for clear-cell renal cell carcinoma in a single European centre applying routine pathology.

BACKGROUND The stage, size, grade, and necrosis (SSIGN) score has been created as an outcome prediction tool for clear-cell renal cell carcinoma (ccRCC) using review pathology. OBJECTIVE We evaluated the prognostic accuracy of the SSIGN score model using routine pathology records. DESIGN, SETTING, AND PARTICIPANTS We retrospectively evaluated pathology records of 1862 consecutive ccRCC patients with complete data including follow-up who had been operated between 1984 and 2006. INTERVENTION Surgical treatment of patients with ccRCC. MEASUREMENTS TNM stage, largest tumour diameter, tumour grade, and presence of histologic tumour necrosis were recorded. ccRCC were categorised according to the SSIGN-score algorithm as 0-15. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method for individual SSIGN-score categories (scores 0-1 and > or =10, respectively, were combined). For evaluation of the prognostic impact of stage, size, grade, and necrosis regarding CSS, a multivariate analysis using a Cox regression model was performed, and for assessment of prognostic accuracy, Harrells concordance index was performed. RESULTS AND LIMITATIONS Median tumour diameter was 5.0 cm (range: 0.6-22 cm). Tumour necrosis was noted in 607 tumours (32.6%). Median follow-up was 72.5 mo (range: 0-281 mo); 359 of 1862 patients (19.3%) died of RCC. Ten-year CSS rates for respective SSIGN scores in our study ranged from 96.5% (scores 0-1) to 19.2% (scores > or =10). pT categories, lymph-node status, distant metastases, high tumour grade (size > or =5 cm), and necrosis were each independent predictors of CSS. The Harrells concordance index was 0.823. Limitations included smaller sample sizes in higher risk categories and limited numbers of patients at risk after 10 yr. CONCLUSIONS Outcome prediction with the SSIGN score using routine pathology records was comparable to the original data based on review pathology. Combining scores into five categories improved discrimination. Our data support the routine use of the SSIGN score in clinical practice with regard to follow-up decisions and patient selection for adjuvant trials.

Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer

To test the accuracy of predicting life‐expectancy (LE) among 19 raters, as the accurate prediction of LE in candidates for definitive therapy for localized prostate cancer is crucial, and little is known of the ability of clinicians to predict LE.

pT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract

Clinicopathologic features predictive of patient outcome in upper urinary tract urothelial carcinoma are not well defined. The aim of this study was to assess the role of pT classification, tumor grade, and vascular invasion in predicting metastasis-free survival. A total of 190 consecutive invasive upper urinary tract urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with respect to pT classification, tumor grade (according to the three-tiered WHO 1973 and the recent two-tiered grading system following the WHO/ISUP consensus classification), as well as presence of lymph and/or blood vessel invasion. Prognostic impact was analyzed using the Kaplan–Meier method and the Log-Rank test. For multivariate testing, a Coxs proportional hazards regression model was used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or 84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered system. The presence of vascular invasion in 72/190 (38%) tumors was associated with high pT classification (P<0.001) and high tumor grade (P<0.001). Disease progression occurred in 39% of patients, with 5- and 10-year metastasis-free survival rates of 56 and 45%, respectively. On univariate analysis, all investigated parameters showed prognostic significance. The negative influence of vascular invasion on patient outcome was strikingly strong in high pT classification and high-grade cancers. On multivariate analysis, pT classification (P<0.001) and vascular invasion (P<0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P=0.06). In conclusion, pT classification and vascular invasion are independent prognostic factors with respect to metastasis-free survival and should be used to guide adjuvant therapy strategies in affected patients. Presence (or absence) of vascular invasion should be commented upon separately in the pathology report.

High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific, metastasis-free, as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients.

Background:In recent years, plasma fibrinogen has been ascribed an important role in the pathophysiology of tumour cell invasion and metastases. A relatively small-scale study has indicated that plasma fibrinogen levels may serve as a prognostic factor for predicting clinical outcomes in non-metastatic renal cell carcinoma (RCC) patients.Methods:Data from 994 consecutive non-metastatic RCC patients, operated between 2000 and 2010 at a single, tertiary academic centre, were evaluated. Analyses of plasma fibrinogen levels were performed one day before the surgical interventions. Patients were categorised using a cut-off value of 466 mg dl−1 according to a calculation by receiver-operating curve analysis. Cancer-specific (CSS), metastasis-free (MFS), as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, a multivariable Cox regression model was performed for all three different endpoints.Results:High plasma fibrinogen levels were associated with various well-established prognostic factors, including age, advanced tumour stage, tumour grade and histologic tumour necrosis (all P<0.05). Furthermore, in multivariable analysis, a high plasma fibrinogen level was statistically significantly associated with a poor outcome for patients’ CSS (hazard ratio (HR): 2.47, 95% confidence interval (CI): 1.49–4.11, P<0.001), MFS (HR: 2.15, 95% CI: 1.44–3.22, P<0.001) and OS (HR: 2.48, 95% CI: 1.80–3.40, P<0.001).Conclusion:A high plasma fibrinogen level seems to represent a strong and independent negative prognostic factor regarding CSS, MFS and OS in non-metastatic RCC patients. Thus, this easily determinable laboratory value should be considered as an additional prognostic factor for RCC patients’ individual risk assessment.

Impact of clinical factors, including a point-of-care nuclear matrix protein-22 assay and cytology, on bladder cancer detection

To determine whether the nuclear matrix protein‐22 (NMP22) assay can improve the accuracy of discriminating between high‐risk patients with and without bladder cancer.

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

Background:The value of a combined index of neutrophil and white cell counts, named derived neutrophil–lymphocyte ratio (dNLR), has recently been proposed as a prognosticator of survival in various cancer types. We investigated the prognostic role of the dNLR in a large European cohort of patients with upper tract urothelial carcinoma (UTUC).Methods:Data from 171 non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Cancer-specific- (CSS) as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the dNLR, multivariate proportional Cox-regression models were applied. Additionally, the influence of the dNLR on the predictive accuracy of the multivariate model was further determined by Harrell’s concordance index (c-index).Results:The median follow-up period was 31 months. An increased dNLR was statistically significantly associated with shorter CSS (log-rank P=0.004), as well as with shorter OS (log-rank P=0.002). Multivariate analysis identified dNLR as an independent predictor for CSS (hazard ratio, HR=1.16, 95% confidence interval, CI=1.01–1.35, P=0.045), as well as for OS (HR=1.21, 95% CI=1.09–1.34, P<0.001). The estimated c-index of the multivariate model for OS was 0.68 without dNLR and 0.73 when dNLR was added.Conclusions:Patients with a high pretreatment dNLR could be predicted to show subsequently higher cancer-specific- as well as overall mortality after surgery for UTUC compared with those with a low pretreatment dNLR. Thus, this combined index should be considered as a potential prognostic biomarker in future.