Low clinical stage renal cell carcinoma: relevance of microvascular tumor invasion as a prognostic parameter

PURPOSE: Renal cell carcinoma is a tumor with unpredictable behavior and defining reliable prognostic factors would be extremely valuable in the clinical setting. Tumor stage, nuclear grade and tumor cell type are the main prognostic clinical parameters available. In this study we evaluated the role of microvascular involvement in the primary lesion for predicting tumor behavior in patients with low stage clinical disease. MATERIALS AND METHODS: A total of 95 patients with clinically localized renal cell carcinoma (stages T1-T2 Nx M0) underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 45 months. The impact of microvascular tumor invasion on disease progression and its correlation with known pathological outcomes (tumor size, nuclear grade and cell type) were studied. RESULTS: Microvascular tumor invasion was observed in 24 patients (25%), of whom 50% had disease recurrence. Of the 71 patients without microvascular invasion only 4 (6%) showed tumor recurrence. When microvascular invasion was correlated with other histological parameters, a significant statistical association was noted with tumor diameter, perirenal fat invasion, macroscopic extension to the renal vein, nuclear grade, lymph node metastasis and sarcomatous elements in the tumor. Multivariate analysis showed that microvascular invasion and the involvement of regional lymph nodes were independent predictors of disease recurrence. Concerning cancer specific survival, microvascular invasion and perirenal fat infiltration were the only factors related to death. CONCLUSIONS: Microvascular invasion is an independent and relevant clinical prognostic parameter for low clinical stage renal cell carcinoma.     

Impact of clinicopathological parameters in patients treated for renal cell carcinoma

PURPOSE: We determined the impact of clinical and pathological factors in the outcome of patients with renal cell carcinoma treated surgically. MATERIALS AND METHODS: We retrospectively reviewed the records of 230 consecutive patients after radical or partial nephrectomy. We analyzed clinical (incidental or symptomatic disease) and pathological (tumor size, histological type, Fuhrman nuclear grade, microvascular invasion and lymph node involvement) parameters. Disease-free and cancer specific survival curves were individualized for each parameter and on multivariate analysis. RESULTS: Median postoperative followup was 34.3 months, median time to recurrence was 22 months and mean overall survival was 130 months. A total of 40 patients (17.3%) presented with local and/or metastatic recurrence and 32 (13.9%) died of the disease. Five-year disease-free and cancer specific survival rates on univariate analysis were 56.7% and 64% for symptomatic tumors, 76.6% and 68% for clear cell carcinoma, 26.9% and 39% for sarcomatoid tumors, 34.7% and 47.5% for high grade tumors, 26.7% and 39.7% for microvascular invasion, 37.5% and 49.1% for tumors larger than 7 cm, and 11% and 32% for lymph node involvement, respectively. On univariate analysis patients with lymph node involvement and microvascular invasion had a poor prognosis. Multivariate analysis showed that the single independent prognostic factor was microvascular invasion. CONCLUSIONS: This study points out different clinical and pathological prognostic factors of survival in patients treated for renal cell carcinoma. Microvascular invasion was the only independent prognostic factor on multivariate analysis.     

Prognostic impact of tumor size on pT2 renal cell carcinoma: an international multicenter experience

PURPOSE: The current tumor classification for renal cell carcinoma classifies pT2 tumors as larger than 7 cm in greatest dimension and limited to the kidney. We examined the current pT2 tumor classification of renal cell carcinoma and determined whether a tumor size cutoff exists that would improve prognostic accuracy. MATERIALS AND METHODS: We studied 706 patients with pT2 renal cell carcinoma treated with surgical extirpation at 9 international academic centers. Data collected from each patient included age at diagnosis, gender, 2002 TNM (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status, histological subtype and disease specific survival. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median followup was 52 months. Univariate Cox regression analysis showed a significant association of tumor size with disease specific survival (HR 1.11, p<0.001). An ideal tumor size cutoff of 11 cm was identified, which led to the stratification of 2 groups with respect to disease specific survival (p<0.0001) with 5 and 10-year survival rates of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm, respectively. The incidence of metastases was significantly greater in the larger than 11 cm group, while Eastern Cooperative Oncology Group performance status, Fuhrman grade and histological subtype were similar. Multivariate Cox regression analysis retained tumor size as an independent prognostic factor and as the strongest prognostic factor for patients with pT2N0M0 disease. CONCLUSIONS: Our data suggest that the current pT2 classification can be improved by subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm. Patients in the proposed pT2bN0M0 group are at higher risk for death from renal cell carcinoma and should be considered for adjuvant therapies. External validation is warranted before suggesting change to the TNM classification.     

Lymphovascular invasion independently predicts increased disease specific survival in patients with transitional cell carcinoma of the upper urinary tract

PURPOSE: We investigated the prognostic impact of lymphovascular invasion (LVI) and traditional prognostic factors for survival in a large series of patients treated surgically for upper tract transitional cell carcinoma (TCC). We also developed a prognostic factors-based model for risk stratification of upper tract TCC. MATERIALS AND METHODS: We identified a study population of 173 consecutive patients treated surgically for upper tract TCC at our institution between 1980 and 2002. We compared LVI with other pathological features and determined the disease specific survival rate. RESULTS: LVI was found in 52 patients (30.1%). As tumor grade and pathological stage increased, the incidence of LVI increased significantly. LVI was found in 12 of 133 patients (9.0%) without lymph node metastasis compared with 40 of 40 patients (100%) with lymph node metastasis. Five and 10-year disease specific survival rates were 84.9% and 80.4% in the absence of LVI, and 40.2% and 21.1% in the presence of LVI, respectively (p <0.001). In multivariate analysis LVI, pathological T stage and tumor grade were independent predictors for disease specific survival. The relative risk of death could be expressed with the formula, exp(0.729 x tumor grade + 1.659 x pathological T stage + 1.160 x LVI). Using this equation the patients were stratified into low risk (grade 1 or 2, LVI negative, stage pT2 or lower), high risk (any tumor grade, LVI positive, stage pT3 or greater) and intermediate risk (all others) groups with significant differences in survival. Five and 10-year disease specific survival rates were 93.0% and 89.4% in the low risk group (82 patients), 66.8% and 62.9% in the intermediate risk group (53 patients), and 25.6% and 0% in the high risk group (38 patients), respectively. CONCLUSIONS: In addition to pathological stage and tumor grade, LVI is an independent prognostic factor for disease specific survival in upper tract TCC. Patients in the high and/or intermediate risk groups may benefit from integrated therapies with surgery and postoperative systemic chemotherapy.     

Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index.

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status x 0.459) + (nuclear grade x 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI < or = 0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.     

Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma

PURPOSE: We determined the prognostic impact of human leukocyte antigen class I on the survival of patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for HLA class I was performed on specimens from 45 patients with clear cell renal cell carcinoma. We performed univariate and multivariate analyses of various factors affecting cause specific survival including HLA class I, Fuhrman grade, TNM stage and tumor size. Furthermore, we compared the survival of patients with HLA class I positive renal cell carcinoma to that of those with down-regulated HLA class I using the Kaplan-Meier method and log rank test. RESULTS: HLA class I was immunohistochemically down-regulated in 17 (37.8%) clear cell renal cell carcinomas. The down-regulation had no correlation with other clinicopathological parameters such as tumor size, perirenal fat invasion, tumor thrombus, TNM stage or nuclear grade. Univariate and multivariate analyses revealed that HLA class I expression, tumor grade and TNM stage were significant factors influencing the disease specific survival of patients with renal cell carcinoma. Patients with HLA class I positive renal cell carcinoma had longer recurrence-free survival than those with down-regulated expression at 5-year followup (95.5% and 61.1%, respectively). CONCLUSIONS: Our data demonstrate that down-regulation of HLA class I on tumor cells is an independent prognostic factor for clear cell renal cell carcinoma. This finding suggests that HLA class I restricted cytotoxic T lymphocytes have an important role in the suppression of renal cell carcinoma.     

肝细胞癌临床病理学特征与手术后长期存活的多因素相关分析

目的评估肝细胞癌（hepatocellular carcinoma，HCC）病理学特征对于长期存活的影响。方法选取1991年1月至2002年6月西南医院实施根治性肝切除，具有完整随访资料和临床资料234例HCC，应用COX比例风险模型单因素和多因素分析影响预后的病理因素，寿命表法计算生存率，Kaplan-Meier乘积极限法绘制生存曲线，log-rank Χ^2检验比较生存时间差异。结果单因素分析提示影响HCC预后的病理因素包括肿瘤大小、微血管侵犯、大血管侵犯、淋巴结侵犯、邻近器官侵犯和Edmonson-Steiner分级，多因素分析发现大血管侵犯（RR：1．728，P〈0．05）、微血管侵犯（RR：1．476，P〈0．05）、淋巴结侵犯（RR：5．010，P〈0．01）、邻近器官侵犯（RR：1．695，P〈0．05）是独立影响HCC预后的重要病理因素。结论大血管侵犯、微血管侵犯、淋巴结侵犯、邻近器官侵犯是影响HCC预后的重要病理学因素。     

A new staging system for locally advanced (pT3-4) renal cell carcinoma: a multicenter European study including 2,000 patients

PURPOSE: We provide an adequate prognostic stratification for locally advanced renal cell carcinoma and propose a new TNM classification. MATERIALS AND METHODS: We analyzed clinical and pathological data on a large series of patients undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 12 European centers. Cancer specific survivals were estimated using the Kaplan-Meier method. The log rank test was used for comparing survival curves and for univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The analysis included 1,969 patients. Median survivor followup was 49 months. Five-year cancer specific survival was 60% for pT3a, 46.2% for pT3b, 10% for pT3c and 12% for pT4 tumors (p <0.0001). According to median survival we identified 3 prognostic groups, including 1--patients with renal vein thrombosis (117 months), fat invasion (98 months) or infradiaphragmatic vena caval thrombosis (67 months), 2--patients with adrenal invasion alone (24 months), renal vein thrombosis plus fat invasion (24 months) or infradiaphragmatic vena cava plus fat invasion (24 months) and 3--patients with renal or infradiaphragmatic caval thrombosis plus adrenal involvement (11 months), supradiaphragmatic vena caval thrombosis (12 months) or Gerota's fascia invasion (12 months). Five-year cancer specific survival rates in groups 1 to 3 were 61%, 35% and 12.9%, respectively (p <0.0001). On multivariate analysis the proposed classification had an independent prognostic value. CONCLUSIONS: Our results suggest the necessity of reclassifying locally advanced renal cell carcinoma according to the 3 described prognostic categories.     

An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage,size, grade and necrosis: the SSIGN score

PURPOSE: Currently outcome prediction in renal cell carcinoma is largely based on pathological stage and tumor grade. We developed an outcome prediction model for patients treated with radical nephrectomy for clear cell renal cell carcinoma, which was based on all available clinical and pathological features significantly associated with death from renal cell carcinoma. MATERIALS AND METHODS: We identified 1,801 adult patients with unilateral clear cell renal cell carcinoma treated with radical nephrectomy between 1970 and 1998. Clinical features examined included age, sex, smoking history, and signs and symptoms at presentation. Pathological features examined included 1997 TNM stage, tumor size, nuclear grade, histological tumor necrosis, sarcomatoid component, cystic architecture, multifocality and surgical margin status. Cancer specific survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to test associations between features studied and outcome. The selection of features included in the multivariate model was validated using bootstrap methodology. RESULTS: Mean followup was 9.7 years (range 0.1 to 31). Estimated cancer specific survival rates at 1, 3, 5, 7 and 10 years were 86.6%, 74.0%, 68.7%, 63.8% and 60.0%, respectively. Several features were multivariately associated with death from clear cell renal cell carcinoma, including 1997 TNM stage (p <0.001), tumor size 5 cm. or greater (p <0.001), nuclear grade (p <0.001) and histological tumor necrosis (p <0.001). CONCLUSIONS: In patients with clear cell renal cell carcinoma 1997 TNM stage, tumor size, nuclear grade and histological tumor necrosis were significantly associated with cancer specific survival. We present a scoring system based on these features that can be used to predict outcome.     

Contribution of grade,vascular invasion and age to outcome in clinically localized renal cell carcinoma

OBJECTIVE: To determine the relative prognostic importance of microvascular invasion in apparently localized renal cell carcinoma (RCC). PATIENTS AND METHODS: A retrospective clinical and pathological review was conducted of 176 consecutive patients identified from pathology records who had a nephrectomy for RCC with a median follow-up of 44 months. Vascular invasion was recorded and categorized by the level of microvascular invasion (MVI), renal vein invasion (RVI) and inferior vena cava invasion (IVCI). Tumour type, grade and size were also assessed. These variables were assessed by univariate and multivariate analysis to determine their effect on disease-free survival. RESULTS: In the univariate analysis tumour size, grade, vascular invasion and young age each predicted reduced disease-free survival. On multivariate analysis for all 176 patients, grade, vascular invasion and young age were the significant independent predictors of reduced disease-free survival. In a subgroup of 149 patients from whom those with very high risk determinants were excluded (those with grade 4 tumours and/or IVCI) most of the risk of metastasis could be accounted for by vascular invasion and young age alone (MVI vs no vascular invasion, hazard ratio 3.18, 95% confidence interval 1.29-7.84; RVI vs no vascular invasion 2.41, 0.989-5.89; and age per year 0.963, 0.94-0.992). CONCLUSIONS: Grade, vascular invasion and young age are the main independent predictors of relapse in clinically localized RCC after nephrectomy. For most patients, who do not have very high risk indicators, the main adverse predictors are vascular invasion and young age. These findings are important when selecting patients for trials of adjuvant therapy and have implications for pathological staging.     

Impact of thrombocytosis and C-reactive protein elevation on the prognosis for patients with renal cell carcinoma

AIM: C-reactive protein (CRP) elevation is reportedly a prognostic factor in patients with renal cell carcinoma (RCC). Thrombocytosis has recently been reported also to be a prognostic factor in RCC and, like CRP, to be related to inflammatory cytokines such as interleukin-6. The aim of this study was to evaluate the importance of both thrombocytosis and CRP elevation in tumor recurrence and prognosis for patients with RCC. METHODS: The clinical records of 178 patients who underwent radical nephrectomy were reviewed. Thrombocytosis was defined as a platelet count >or=350,000/mm(3), and CRP elevation was defined as a CRP level >or=1.0 mg/dL. Disease-free survival and cause-specific survival rates were calculated. Independent predictors for recurrence and prognosis were determined. RESULTS: Patients with thrombocytosis and patients with elevated CRP levels had significantly higher pathological T stage, clinical stage, tumor size, histological grade, and percentage of microvascular invasion than did patients without THC and patients with CRP levels <1.0 mg/dL, respectively. There was a significant correlation between platelet counts and CRP levels. Multivariate analysis showed that distant metastasis, tumor size, grade 3 components, and CRP elevation were independent predictors for prognosis but thrombocytosis was not. In N0M0 RCC patients, tumor size, microvascular invasion, and CRP elevation were independent predictors for recurrence. CRP elevation and tumor size were independent predictors for prognosis. CONCLUSIONS: Platelet count and CRP level are strongly correlated in patients with RCC, but only CRP elevation is an independent predictor for recurrence and prognosis.     

Valor pronóstico de la invasión microvascular en la predicción de la supervivencia en el carcinoma de células renales

ObjectiveTo assess microvascular tumor invasion and other clinical and histological parameters as potential prognostic factors in surgically treated renal cell carcinoma.Materials and methodsSurgical specimens from 238 consecutive patients who underwent radical or partial surgery between 1990 and 2006 were retrospectively evaluated. The series included clinically localized or metastatic renal cell carcinoma (pT1-4; N0-1; M0-1). Disease-free and cancer-specific survival assessments were the end points with median follow-up of 75 months (range 1-189 months). Variables studied included: age, sex, tumor size, TNM 2010 classification, Fuhrman grade, histological subtype and microvascular tumor invasion.ResultsMicrovascular tumor invasion was observed in 79 patients (33,2%) and was significantly associated with age (P = .010), tumor size (P = .000), Fuhrman grade (P = .000), pT stage 2010 (P = .000), N stage 2010 (P = .000) and M stage 2010 (P = .000). Multivariate analyses determined that sex, Fuhrman grade, pT stage 2010 and histological subtipe were independent prognostic factors of disease-free survival, while sex, Fuhrman grade, pT stage 2010, M stage 2010, histological subtype and microvascular invasion were prognostic factors for cancer-specific survival.ConclusionsOur study shows that microvascular tumor invasion is an independent prognostic factor for cancer-specific survival in surgically treated patients with renal cell carcinoma.     

Multi-institutional validation of a symptom based classification for renal cell carcinoma

PURPOSE: We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study. MATERIALS AND METHODS: A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001). CONCLUSIONS: This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.     

Prognostic value of venous tumor thrombus in renal cell carcinoma

ObjectiveTo evaluate the prognostic value of venous tumor thrombus in renal cell carcinoma.Material and methodsA retrospective study of 167 patients with renal cell carcinoma and stage pT3 who underwent radical nephrectomy and extended lymphadenectomy from July 1969 to May 2008 was conducted. Patients with any kind of venous involvement were selected for the analysis (73 patients; 43.7%). The Kaplan Meier survival curves and log-rank test for comparisons were used for the survival analysis. Multivariate analysis was done by Cox regression.ResultsLymph node involvement was present in 30 patients (41.1%) and metastatic disease in 9 patients (12.3%). The most frequent histologic renal cell carcinoma subtype was 50 (68.5%) conventional carcinoma, followed by nondifferentiated in 11 (15.5%), and chromophobe in 9 (12.3%). High grade tumors (Furhman 3-4) were present in 57% of the cases. Venous thrombus level extended to renal vein in 61 patients (83.6%), to inferior vena cava in 9 patients (12.3%) and to the cardiac right atrium in 3 cases (4.1%). The survival analysis showed worse survival in those patients with venous tumor thrombosis (p=.001) and with vein wall invasion (p=.0042), but not in function on the level of the thrombus (p=.12). The multivariate analysis identified the Furhman grade and venous tumor thrombosis as independent survival prognostic factors.ConclusionsIn our series, venous tumor thrombosis, together with the Furhman nuclear grade, is an independent survival prognostic factor. However, neither cephalic extension of the thrombus nor the invasion of the vein wall showed independent prognostic value.     

Validation of a postoperative prognostic model consisting of tumor microvascular invasion, size, and grade to predict disease-free and cancer-specific survival of patients with surgically resected renal cell carcinoma

Objectives:   To determine the value of microvascular invasion, tumor size, and Fuhrman grade to predict the survival of patients with surgically resected renal cell carcinoma (RCC).
Methods:   A total of 771 consecutive patients (T1–4, Nx, M0) were retrospectively reviewed. For each patient with RCC, the prognostic Sao Paulo score (SPS) was calculated using the following variables: tumor size (>7 cm vs ≤7 cm), nuclear grading, and microvascular invasion. On the basis of SPS, patients were subdivided into low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups. Disease-free survival (DFS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Median follow-up was 80 months.
Results:   Median follow-up was 80 months. DFS rates after 5 years were 91.2%, 61.3%, and 51.9% in the original SPS LR, IR, and HR groups, respectively. CSS rates after 5 years were 94.3%, 79.8%, and 58.7%, respectively ( P  < 0.001). Each original SPS constituent revealed a significant influence on DFS and CSS in the multivariate analysis. By modification of the cut-off value of the maximum tumor size from 7 to 5 cm the predictive value of the SPS sum score was marginally enhanced. Using a cut-off value of 5 cm also resulted in a relatively better discrimination between the IR and the HR group regarding DFS and CSS.
Conclusions:   Stratifying RCC patients by SPS into LR, IR, and HR groups provides a clinically useful tool for outcome analysis and risk assessment. However, the prognostic value of the SPS could be enhanced by including a maximum tumor size with a cut-off at 5 cm into the sum score.     

The impact of a 4 cm. cutoff point for stratification of T1N0M0 renal cell carcinoma after radical nephrectomy

PURPOSE: The 1997 TNM classification defines T1 tumors as those smaller than 7 cm. Recently, a cutoff point of 4 cm. has been proposed to create a subclass of T1 tumors. We evaluated the validity of this cutoff point by assessing the pathological findings and prognoses of patients with T1N0M0 renal cell carcinoma following radical nephrectomy. MATERIALS AND METHODS: We reviewed the hospital charts of 333 patients with T1N0M0 tumors, followed as long as 282 months (median 63) after radical nephrectomy. The validity of tumor size cutoff point for predicting survival outcome was tested in relation to other prognostic factors, including patient age, tumor position, nuclear grade, tumor histopathology and degree of microscopic venous invasion. RESULTS: During followup 32 patients (9.6%) had tumor recurrence and 21 (6.3%) died of renal cell carcinoma. A 5 cm. cutoff point maximized the differences in cancer specific survival rates and a 4 cm. cutoff point maximized the differences in disease-free survival rates. Tumor size was directly related to microscopic venous invasion and nuclear grade, which are significant prognostic factors, and a 4 cm. cutoff point enhanced these relationships. CONCLUSIONS: Tumor size is an important prognostic factor for patients with T1N0M0 renal cell carcinoma. A cutoff point of 4 cm. is practical for dividing the T1N0M0 classification into T1a and T1b subclasses.     

Prognostic significance of tumor grade for renal cell carcinoma

BACKGROUND: The natural history and prognosis of renal cell carcinoma cannot be predicted. Based on the Japanese classification system, the value of nuclear grade were assessed as a possible prognostic factor for renal cell carcinomas. METHODS: In this retrospective study of 116 patients with renal cell carcinoma, radical nephrectomy was performed. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using Cox's proportional hazard model. RESULTS: Distribution by stage and grade in the population of renal cell carcinomas was as follows: pT1 in 13 cases (11.3%), pT2 in 65 cases (56.5%), pT3 in 36 cases (31.3%) and pT4 in one case (0.9%) and grade 1, 28 (24.1%), grade 2, 69 (59.5%) and grade 3, 16 (13.8%). Three cases could not be determined because of pre-operative embolization of the renal cell carcinomas. Nuclear grade was correlated with stage (P=0.0002), the presence of perirenal fat involvement (P=0.003) and metastases (P=0.007). A significant difference in survival was found between grades 1 and 3 (P=0.0001) and grades 2 and 3 (P=0.0001), respectively. Survival was significantly correlated with sex (P=0.0125), tumor size (P=0.0001), the presence of lymph node metastasis (P=0.0001), renal vein involvement (P=0.0001), perirenal fat involvement (P=0.002) or distant metastasis (P=0.0001). The multivariate analysis showed that the occurrence of tumor grade (P=0.0006) or distant metastasis were independent prognostic values. CONCLUSION: The observations lead us to conclude that the nuclear grade according to the Japanese classification system appears to be of reliable prognostic value for renal cell carcinomas.     

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.     

Prognostic significance of bladder tumor history and tumor location in upper tract transitional cell carcinoma

PURPOSE: We studied prognostic factors for 5-year disease specific and recurrence-free survival in patients treated for upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: Since July 1987, 72 patients with a mean age of 58.9 years have undergone nephroureterectomy with bladder cuff excision. Median followup was 62.2 months (range 6 to 192). Patient age, sex, detection duration and mode, bladder tumor history, smoking habit, stone disease history, and tumor stage, grade and location were evaluated as prognostic factors. RESULTS: Overall 5-year disease specific and recurrence-free survival rates were 74.9% and 67.8%, respectively. Univariate analysis revealed anemia, positive bladder tumor history, T stage, grade and tumor location in the upper tract as significant prognostic factors. On multivariate analysis T stage, grade and tumor location in the urothelium were the only significant variables for the 5-year disease specific and recurrence-free survival rates. CONCLUSIONS: High tumor stage and grade, and ureteral location were significantly associated with worse disease specific and recurrence-free survival in patients with upper urinary tract transitional cell carcinoma. Our results may help define the patient groups that need adjuvant therapy and they may form a basis for further controlled studies.