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Item does not contain fulltext, BACKGROUND: Currently two pretreatment prognostic models with limited accuracy (65-67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC). OBJECTIVE: We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC. DESIGN, SETTING, AND PARTICIPANTS: The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers. MEASUREMENTS: The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes. RESULTS AND LIMITATIONS: Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr. CONCLUSIONS: Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC.

Item does not contain fulltext, BACKGROUND: The prognostic significance of venous tumor thrombus extension in patients with renal cell carcinoma (RCC) is a matter of many controversies in the current literature. OBJECTIVE: To evaluate the prognostic role of inferior vena cava (IVC) involvement in a large series of pT3b and pT3c RCCs. DESIGN, SETTING, AND PARTICIPANTS: A total of 1192 patients from 13 European institutions underwent a radical nephrectomy for pT3b and pT3c RCC between 1982 and 2003. The patients were evaluated in a retrospective manner. Age, gender, clinical symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, tumor size, adrenal invasion, perinephric fat invasion, histological type, and Fuhrman grade were reviewed. The log-rank and Cox uni- and multivariate regression analyses were used to evaluate prognostic factors for overall survival. MEASUREMENTS: Overall survival and prognostic factors for overall survival in patients with RCC extending to the renal vein (RV) or to the IVC. RESULTS AND LIMITATIONS: The median follow-up was 61.4 mo (56.3-66.5 mo). The mean age was 63.2 yr. The mean tumor size was 8.9 cm. Group 1 (Gr 1) included 933 patients with a renal vein tumor thrombus (78.3%), Group 2 (Gr 2) included 196 patients with a subdiaphragmatic IVC tumor thrombus (16.4%), and Group 3 (Gr 3) included 63 patients with a supradiaphragmatic IVC tumor thrombus (5.3%). Median survival was 52 mo for Gr 1, 25.8 mo for Gr 2, and 18 mo for Gr 3. In univariate analysis, Gr 1 had a significantly better overall survival than Gr 2 (p<0.001) and Gr 3 (p

Item does not contain fulltext, OBJECTIVE: To quantify the survival disadvantage related to the presence of exclusive nodal metastases (eNM) in patients with otherwise non-metastatic (M0) renal cell carcinoma (RCC). PATIENTS AND METHODS: Data were retrieved from 12 institutional databases and yielded 3507 patients with T1-3N1-2M0 RCC treated with partial or radical nephrectomy. Cox regression analyses relied on T stage, Fuhrman grade and presence of eNM. Data were analysed using univariable, multivariable and stratified analyses. RESULTS: Overall 165 (4.7%) patients had eNM; of 2023 patients of stage T1, 23 (1.1%) had eNM, vs 20 of 448 (4.5%) for T2 and 122 of 993 (12.3%) for T3. In univariable analyses the presence of eNM increased the rate of cancer specific mortality (CSM) by 7.1 times. After adjusting for T stage and Fuhrman grade, in all patients eNM increased the rate of CSM by 3.2 times. In stratified analyses adjusted for Fuhrman grade, the increase in CSM related to the presence of eNM was 28.9, 4.3 and 2.5 times (all P < 0.001) for stages T1, T2 and T3, respectively. CONCLUSIONS: From the prognostic perspective, staging lymphadenectomy appears of most value in patients with T1-2 RCC, but the low prevalence of eNM questions the practical applicability of nodal staging in those patients. Conversely, in patients with T3 RCC, the prevalence and the prognostic impact of eNM might make a staging lymphadenectomy worthwhile.

Item does not contain fulltext, PURPOSE: Fuhrman grade represents a key determinant of the natural history of small renal masses that represent renal cell carcinoma. We tested whether renal mass biopsy prediction of Fuhrman grade in the nephrectomy specimen could be safely substituted for by an accurate statistical model. To date the best available model has shown poor accuracy (55.6%), which is close to flipping a coin (50%) and clearly inadequate for use in clinical practice. MATERIALS AND METHODS: We identified 1,139 patients with T1aN0M0 renal cell carcinoma treated with partial or radical nephrectomy at 11 participating institutions from 1989 to 2004. This cohort was used in univariate and multivariate logistic regression models predicting high Fuhrman grade (III-IV) at nephrectomy. Predictors included age at diagnosis, gender, tumor size and symptom classification. Multivariate logistic regression coefficients were used to generate a nomogram. RESULTS: The rate of Fuhrman grade III-IV in patients with T1aN0M0 renal cell carcinoma was 12.3%. Stratifying patients with Fuhrman grade III-IV by age, gender, histological subtypes and sample size failed to reveal statistically significant differences. On univariate analysis predicting Fuhrman grade III-IV at nephrectomy only tumor size was a statistically significant predictor (p = 0.05). The most accurate multivariate nomogram for Fuhrman grade III-IV prediction was 58.3% (95% CI 57.8-58.9) accurate. Of all tested predictors only tumor size achieved independent predictor status (p = 0.009). CONCLUSIONS: Our analysis derived in European patients shows that statistical models cannot safely replace renal mass biopsy based prediction of Fuhrman grade III-IV at nephrectomy. Our findings corroborate a report from the United States in which a similar model had 55.6% accuracy. Jointly the studies indicate that statistical models are unreliable and cannot safely be substituted for renal mass biopsy in North American or European patients.

Item does not contain fulltext, PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stages treated with nephrectomy. We applied conditional survival methodology to a previously reported posttreatment nomogram predicting survival after nephrectomy for patients with renal cell carcinoma stage I to IV. We used the same predictor variables that were integrated in the original multivariable Cox regression models, namely TNM stage, Fuhrman grade, tumor size and symptom classification. To validate the conditional survival nomogram we used an independent cohort of 3,560 patients from 15 institutions. RESULTS: The 5-year survival of patients immediately after nephrectomy was 74.2%, which increased to 80.4%, 85.1%, 90.6% and 89.6% at 1, 2, 5 and 10 years after nephrectomy, respectively. The predicted probabilities varied by as much as 50% when, for example, predictions of renal cell carcinoma specific mortality at 10 years were made after nephrectomy vs 5 years later. Within the external validation cohort the accuracy of the conditional nomogram was 89.5%, 90.5%, 88.5% and 86.7% at 1, 2, 5 and 10 years after nephrectomy. CONCLUSIONS: We developed (2,530) and externally validated (3,560) a conditional nomogram for predicting renal cell carcinoma specific mortality that allows consideration of the length of survivorship. Our tool provides the most realistic prognosis estimates with high accuracy.

Item does not contain fulltext, OBJECTIVE: To identify clinical variables that can accurately predict the presence of distant metastases in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Age, symptom classification, tumour size and the prevalence of distant metastases at diagnosis before nephrectomy were available for 5376 patients with pathologically confirmed RCC. The data of 2660 (49.5%) patients from 11 centres were used to develop a multivariable logistic regression model-based nomogram predicting the individual probability of distant metastases. The remaining data from 2716 (50.5%) patients from three institutions were used for external validation. RESULTS: In the development cohort, 269/2660 (10.1%) had distant metastases, vs 285/2716 (10.5%) in the external validation cohort. Symptom classification and tumour size were independent predictors of distant metastases in the development cohort; age was not an independent predictor. A nomogram based on symptom classification and tumour size was 85.2% accurate in predicting the individual probability of distant metastases in the external validation cohort. CONCLUSION: Although distant metastases might be easily identifiable in some patients, their diagnosis might be a challenge in others. The current nomogram provides a simple, user-friendly and, most importantly, an accurate tool aimed at predicting the probability of distant metastases in patients with RCC.