Critical analysis of a simplified Fuhrman grading scheme for prediction of cancer specific mortality in patients with clear cell renal cell carcinoma--Impact on prognosis.

INTRODUCTION AND OBJECTIVES: The traditional 4-tiered Fuhrman grading system (FGS) is widely accepted as histopathological classification for clear cell renal cell carcinoma (ccRCC) and has shown prognostic value. As intra- and inter-observer agreement are sub-optimal, simplified 2- or 3-tiered FGSs have been proposed. We aimed to validate these simplified 2- or 3-tiered FGSs for prediction of cancer-specific mortality (CSM) in a large study population from 2 European tertiary care centers. METHODS: We identified and followed-up 2415 patients with ccRCC who underwent radical or partial nephrectomy in 2 European tertiary care centers. Univariable and multivariable analyses and prognostic accuracy analyses were performed to evaluate the ability of several simplified FGSs (i.e. grades I + II vs., grades III + IV, grades I + II vs. grade III and grade IV) to predict CSM. RESULTS: Independent predictor status in multivariate analyses was proved for the simplified 2-tiered FGS (high-grade vs. low-grade), for the simplified 3-tiered FGS (grades I + II vs. grade III and grade IV) as well as for the traditional 4-tiered FGS. The prognostic accuracy of multivariable models of 77% was identical for all tested models. Prognostic accuracy of the model without FG was 75%. CONCLUSIONS: A simplified 2- or 3-tiered FGS could predict CSM as accurate as the traditional 4-tiered FGS in a large European study population. Application of new simplified 2- or 3-tiered FGS may reduce inter-observer-variability and facilitate clinical practice without compromising the ability to predict CSM in ccRCC patients after radical or partial nephrectomy.

[Postoperative prognosis of chromophobic renal cell carcinoma: comparative analysis of the multinational CORONA database]. / Die postoperative Prognose des chromophoben Nierenzellkarzinoms : Eine vergleichende Analyse anhand der multinationalen CORONA-Datenbank.

BACKGROUND: The chromophobe subtype represents the third most common histological subtype of renal cell carcinoma (chRCC). Due to the rarity of this subtype only one publication regarding the specific analysis of clinical and histopathological criteria as well as survival analysis of more than 200 patients with chRCC is known to date. MATERIALS AND METHODS: A total of 6,234 RCC patients from 11 centres who were treated by (partial) nephrectomy are contained in the database of this multinational study. Of the patients 259 were diagnosed with chRCC (4.2 %) and thus formed the study group for this retrospective investigation. These subjects were compared to 4,994 patients with a clear cell subtype (80.1 %) with respect to clinical and histopathological criteria. The independent influence of the chromophobe subtype regarding tumor-specific survival and overall survival was determined using analysis by Cox proportional hazards regression models. The median follow-up was 59 months (interquartile range 29-106 months). RESULTS: The chRCC patients were significantly younger (60 vs. 63.2 years, p < 0.001), more often female (50 vs. 41 %, p = 0.005) and showed simultaneous distant metastases to a lesser extent (3.5 vs. 7.1 %, p = 0.023) compared to patients with a clear cell subtype. Despite a comparable median tumor size a ≥ pT3 tumor stage was diagnosed in only 24.7 % of the patients compared to of 30.5 % in patients with a clear cell subtype (p = 0.047). In addition to the clinical criteria of age, sex and distant metastases, the histological variables pTN stage, grade and tumor size showed a significant influence on tumor-specific and overall survival. However, in the multivariable Cox regression analysis no independent effect on tumor-specific mortality (HR 0.88, p = 0.515) and overall mortality (HR 1.00, p = 0.998) due to the histological subtype was found (c-index 0.86 and 0.77, respectively). CONCLUSIONS: Patients with chRCC and clear cell RCC differ significantly concerning the distribution of clinical and histopathological criteria. Patients with chRCC present with less advanced tumors which leads to better tumor-specific survival rates in general; however, this advantage could not be verified after adjustment for the established risk factors.

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 Harrell's 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.

[Advanced bladder cancer in elderly patients. Prognostic outcomes and therapeutic strategies]. / Das fortgeschrittene Urothelkarzinom der Harnblase beim älteren Patienten. Ein Überblick über Inzidenz, Prognose und therapeutische Möglichkeiten.

INTRODUCTION: Age is suggested to be the greatest single risk factor for developing urothelial carcinoma of the bladder (UCB). This review presents an overview of the incidence, prognosis, surgical and medical therapy of UCB in elderly patients (> 65 years). RESULTS: Elderly patients have an approximate 11-fold increase in the incidence and a 15-fold increase in UCB mortality when compared to younger individuals. However, adequate surgical or medical treatment is less often or delayed offered to elderly patients. In properly selected cases, similar surgical outcomes and complication rates are reported in elderly patients, regardless of the type of urinary diversion. Application of perioperative systemic chemotherapy is dependent on physiologic deterioration and comorbidities. An adequate, restrictive case selection and early proactive postoperative rehabilitation are important factors to achieve good results. CONCLUSIONS: In adequately selected elderly patients, radical cystectomy and urinary diversion as well as systemic chemotherapy are feasible, safe and efficacious treatment options for advanced UCB.

Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma.

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.

Patterns of invasion and histological growth as prognostic indicators in urothelial carcinoma of the upper urinary tract.

The biological significance of squamous and glandular differentiation and different patterns of invasion in upper urinary tract urothelial carcinoma is unclear. We reviewed 268 cases of consecutive upper urinary tract carcinomas with respect to the presence of squamous and/or glandular differentiation and different patterns of invasion (nodular, trabecular, and infiltrative) and correlated data with patient outcome. Squamous or glandular differentiation occurred in 47/268 (18%) tumors and its presence correlated with high tumor stage (P<0.001) and grade (P<0.001). Invasive patterns were nodular in 49/227 (22%), trabecular in 95/227 (42%), and infiltrative in 83/227 (37%) tumors. The nodular pattern prevailed in low stage (P<0.001) and low-grade (P<0.001) tumors, whereas the infiltrative pattern prevailed in high stage (P<0.001) and high-grade (P<0.001) tumors. Multivariate analysis proved that tumor stage (P<0.001) and the infiltrative pattern (P<0.001) are independent predictors of metastasis-free survival, whereas tumor grade and squamous and glandular differentiation lacked independent influence on patient outcome. In conclusion, the infiltrative pattern of invasion significantly correlated with advanced disease and poor patient outcome. In contrast, the presence of squamous and/or glandular invasion did not prove independent influence on patient outcome. The pattern of invasion should be commented upon separately in the pathology report.