Karin Kampel-Kettner

Histologic Tumor Necrosis Is an Independent Prognostic Indicator for Clear Cell and Papillary Renal Cell Carcinoma

Histologic tumor necrosis (TN) has been reported to indicate a poor prognosis for different human cancers. In papillary renal cell carcinoma (RCC), data regarding the prognostic impact of TN are conflicting. We retrospectively studied the pathology records of 2,333 consecutive patients who underwent nephrectomy from 1984 to 2006 at a single tertiary academic center. In multivariate analyses regarding clear cell RCC, the presence of histologic TN was an independent negative prognostic factor for metastasis-free (hazard ratio [HR], 2.32; confidence interval [CI], 1.86-2.9; P < .001) and overall (HR, 1.52; CI, 1.31-1.76; P < .001) survival. Regarding papillary RCC, the presence of histologic TN represented an independent predictor of metastasis-free (HR, 5.22; CI, 2.2-12.5; P < .001) and overall (HR, 1.69; CI, 1.11-2.58; P = .015) survival. Our findings suggest that the presence of TN is an independent predictor of clinical outcome in clear cell and papillary RCC. Thus, histologic TN might be a reliable prognostic indicator and should, therefore, routinely be examined during pathologic analysis of RCC specimens.

External Validation of the Leibovich Prognosis Score for Nonmetastatic Clear Cell Renal Cell Carcinoma at a Single European Center Applying Routine Pathology

PURPOSE The Leibovich prognosis score was developed as a prognostic tool for metastatic disease after radical nephrectomy for clear cell renal cell carcinoma using pathology review. However, this scoring system has never been externally validated. We externally validated its prognostic accuracy using routine pathology reports. MATERIALS AND METHODS We retrospectively evaluated data from the routine pathology records of 1,754 consecutive patients with nonmetastatic clear cell renal cell carcinoma operated on between 1984 and 2006 at a single tertiary academic center. Clear cell renal cell carcinoma cases were categorized as 0 to 11 by the Leibovich prognosis score and further stratified into low, intermediate and high risk groups. Metastasis-free survival was assessed using the Kaplan-Meier method. To evaluate the prognostic impact a multivariate Cox regression model was used and prognostic accuracy was determined using Harrells concordance index. RESULTS Median followup was 82 months (IQR 39-142). Metastasis developed in 375 of the 1,754 patients (21.4%). The 10-year metastasis-free survival rate for Leibovich scores in our study ranged from 95% for scores of 0 and 1 to 12% for scores of 8 or greater. Pathological T stage, N stage, low tumor grade, large tumor diameter and histological tumor necrosis were independent predictors of metastasis-free survival (p <0.001). Harrells concordance index was 0.778. CONCLUSIONS Risk prediction by the Leibovich prognosis score using routine pathological results was comparable to that of the original data based on pathology review. Our data support using the Leibovich prognosis score in clinical practice for followup decisions and patient selection for adjuvant treatment trials.

Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer

BackgroundSingle circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC.MethodsBlood of 40 patients with renal tumors was subjected to ScreenCell® filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH.ResultsCNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX.ConclusionsThe majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell® filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.

Prognostic Value of the Leibovich Prognosis Score Supplemented by Vascular Invasion for Clear Cell Renal Cell Carcinoma

PURPOSE We assessed whether supplementing the Leibovich prognosis score with vascular invasion would improve prognostic value to predict metastatic disease in patients with nonmetastatic clear cell renal cell carcinoma. MATERIALS AND METHODS We retrospectively evaluated the pathology records of 1,754 patients with nonmetastatic clear cell renal cell carcinoma treated with surgery between 1984 and 2006 at a single tertiary academic center. The Leibovich prognosis score was supplemented by additional scoring for vascular invasion. Metastasis-free survival was assessed using the Kaplan-Meier method for each score category. A Cox regression model was used for multivariate testing. Predictive accuracy was determined by the Harrell concordance index and decision curve analysis. RESULTS Median followup was 84 months. Ten-year metastasis-free survival probability for a score of 0 to 1 and 2 to 8 or greater was 95%, 83%, 78%, 81%, 69%, 51%, 15% and 13%, respectively. The concordance index was 0.792 compared to 0.778 from our external validation of the Leibovich prognosis score using routine pathological findings (p <0.05). Decision curve analysis also favored the predictive ability of the novel model. CONCLUSIONS Adding vascular invasion improved the predictive accuracy of our validation data by 1.4% over that of the Leibovich prognosis score. Patients with a score of 7 or greater had a more than 85% probability of metastatic disease at 10 years. Thus, they could be considered candidates for adjuvant treatment trials.

Trends of stage, grade, histology and tumour necrosis in renal cell carcinoma in a European centre surgical series from 1984 to 2010

Aims To analyse renal cell carcinoma (RCC) stage, grade, histology and necrosis migration in a large European centre series over the last 27 years. Methods The pathology reports of 2739 consecutive patients with RCC who underwent nephrectomy from 1984 to 2010 at the institution of the authors were systematically re-evaluated. Patients were pooled into five time groups according to the date of surgery: group 1: 1984–1989, group 2: 1990–1994, group 3: 1995–1999, group 4: 2000–2004 and group 5: 2005–2010, respectively. Changes in pT categories according to WHO 2010 classification, tumour grade, histological subtype and presence of tumour necrosis (TN) were evaluated. Results Small pT1a tumours were found in 62/485 (12.8%) and 312/639 (48.8%) patients in groups 1 and 5, respectively (p<0.001). Advanced tumour stages (pT3a-4) were found in 306/485 (63.1%) and 171/639 (26.8%) patients in groups 1 and 5, respectively (p<0.001). The number of grade 3/4 tumours increased from 62/485 (12.7%) and 130/639 (20.3%) in groups 1 and 5, respectively, whereas the number of grade 1 tumours decreased over time (p<0.001). There has been a significant histological migration for the chromophobe subtype from 1.1% to 4.3% (p=0.002). The frequency of the presence TN decreased from 41.7% in group 1 to 32.7% in group 5 (p<0.001). Conclusions In contrast to data from Australia but similar to data from US cohorts, a statistically significant stage migration towards small RCCs was observed in this European cohort. Significant changes in tumour grade, histological subtype and TN were also observed.

Comparison of the 2002 and 2010 TNM classification systems regarding outcome prediction in clear cell and papillary renal cell carcinoma.

Aims:  A novel version of the tumour–node–metastasis (TNM) classification system for renal cell carcinoma (RCC) was introduced in 2010, although the prognostic significance with regard to different histological subtypes has not been explored. Therefore, the aim of our study was to compare the predictive ability of the 2002 and 2010 versions of the TNM classification system for clear cell and papillary RCC.

Predictive ability of the 2002 and 2010 versions of the Tumour-Node-Metastasis classification system regarding metastasis-free, cancer-specific and overall survival in a European renal cell carcinoma single-centre series.

Whats known on the subject? and What does the study add?

Comparison of the 2002 and 2010 version of the TNM classification system regarding the prediction of metastasis-free survival in patients with renal cell carcinoma.

448 Background: A new version of the TNM classification system for renal cell carcinoma (RCC) has been introduced in 2010 by the American Joint Committee on Cancer (AJCC). However, data for its ability to predict metastasis-free survival in RCC patients from validation studies of independent cohorts are sparse. Therefore, we decided to compare the predictive ability of the 2010 vs. the 2002 version of the TNM classification system. METHODS Pathological reports of 2595 patients with uni- or bilateral synchronous non-metastatic (pT1-4N0M0) RCCs, treated with radical nephrectomy or nephron sparing surgery between 1984 and 2010 at a single tertiary academic center, were re-evaluated. Metastasis-free survival (MFS) was assessed using the Kaplan-Meier method and pairwise log-rank tests. RESULTS Mean follow up was 95 (0-322) months and 430 (16.6%) patients were found to develop metastatic disease from RCC. Pairwise comparisons revealed statistically significant differences in MFS between adjacent 2002 primary tumor classifications, including pT1a vs. pT1b (p<0.001), pT1b vs. pT2 (p=0.029), pT3a vs. pT3b (p<0.001), and pT3c vs. pT4 (p=0.007) but excluding, pT2 vs. pT3a (p=0.963) and pT3b vs. pT3c (p=0.968). With the changes to the 2010 primary tumor classification different trends in statistical significance were observed in pairwise comparisons, including pT1a vs. pT1b (p<0.001), pT3a vs. pT3b (p=0.001) but excluding pT1b vs. pT2a (p=0.062), pT2a vs. pT2b (p=0.856), pT2b vs. pT3a (p=0.395), pT3b vs. pT3c (p=0.891) and pT3c vs. pT4 (p=0.933). CONCLUSIONS The 2010 version of the TNM classification system remains a robust predictor of MFS compared to the 2002 version. However, the 2010 version showed less discriminative power in higher pT-stages compared to the 2002 version of the TNM classification system.

SARCOMATOID TRANSFORMATION AND COLLECTING SYSTEM INVASION: INDEPENDENT PROGNOSTIC INDICATORS IN PATIENTS WITH RENAL CELL CARCINOMA?

1207 SARCOMATOID TRANSFORMATION AND COLLECTING SYSTEM INVASION: INDEPENDENT PROGNOSTIC INDICATORS IN PATIENTS WITH RENAL CELL CARCINOMA? Thomas Chromecki*, Georg C Hutterer, Karin Kampel-Kettner, Arwin Imamovic, Peter Rehak, Cord Langner, Karl Pummer, Richard Zigeuner. Graz, Austria. INTRODUCTION AND OBJECTIVE: Outcome prediction of patients with renal cell carcinoma (RCC) is mainly based on stage and grade. Regarding adjuvant treatments, additional prognostic indicators may gain importance. We evaluated the prognostic impact of sarcomatoid transformation and invasion of the collecting system. METHODS: The pathology reports of 2394 resected RCCs from 2333 consecutive patients (983 females, 1350 males) operated between 01/1984 and 12/2006 at our institution were systematically re-evaluated with regard to pT-categories (TNM 2002), tumor grades, tumor necrosis, invasion of the collecting system, histological subtypes and sarcomatoid transformation. A central pathology review was not performed. A multivariate analysis regarding metastasis-free survival including the above mentioned histopathological parameters, age, and