Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma.

The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC. The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival. The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001). The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.

Lam JS ，Shvarts O ，Said JW ，Pantuck AJ ，Seligson DB ，Aldridge ME ，Bui MH ，Liu X ，Horvath S ，Figlin RA ，Belldegrun AS ... -  《CANCER》

Performance status and cytoreductive nephrectomy: redefining management in patients with poor performance.

An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2/3 can quantify cancer patients' well being and may be used to select patients for treatment. The objective of the current study was to investigate the outcomes of cytoreductive nephrectomy (CN) for patients who have an impaired performance status (ECOG PS 2/3). Patients who underwent CN for renal cell carcinoma (RCC) between 1989 and 2006 were identified. Patient records were reviewed for age, symptoms, ECOG PS, tumor size, stage, grade, histology, sarcomatoid features, lymph node metastasis, site of metastasis, and the presence of bone metastases (BM) in weight-bearing structures. The relation of ECOG PS to outcome variables was evaluated. Four hundred eighteen patients underwent CN, including 117 patients who had an ECOG PS of 0, 274 patients who had an ECOG PS of 1, and 27 patients who had an ECOG PS of 2/3. Patients who had a worse ECOG PS were younger, had higher tumor classification and grade, and more frequently demonstrated anemia and BM. Only 37.5% of patients who had an ECOG PS of 2/3 experienced an improvement in performance in the postoperative period, and only 57.5% went on to receive systemic therapy, of whom none attained an objective responses. The median disease-specific survival for patients who had an ECOG PS of 0, 1, and 2/3 was 27 months, 13.8 months, and 6.6 months, respectively (P<.001). Patients who had an ECOG PS of 2/3 could be stratified further by the presence or absence of BM into 2 groups (median disease-specific survival: 17.7 months and 2.1 months, respectively; P = .006). Surgery in patients who have a poor performance may serve a palliative function but should be performed with caution because of the poor outcome of such patients. ECOG PS is influenced strongly by BM. A subset of patients with an ECOG PS of 2/3 that are symptomatic specifically from BM may derive greater benefit from CN than patients who hare symptomatic because of visceral metastases.

Shuch B ，La Rochelle JC ，Wu J ，Klatte T ，Riggs SB ，Kabbinavar F ，Belldegrun AS ，Pantuck AJ ... -  《-》

pT1 clear cell renal cell carcinoma: a study of the association between MIB-1 proliferative activity and pathologic features and cancer specific survival.

The majority of patients with pT1 clear cell renal cell carcinoma (RCC) are cured with nephrectomy. However, a few patients will die of RCC. In several studies, MIB-1 proliferative activity was identified as an independent predictor of survival in patients with RCC. The objective of the current study was to examine MIB-1 proliferative activity in a large series of patients with pT1 clear cell RCC who were treated uniformly with radical nephrectomy, and to examine the association between proliferative activity and cancer specific survival in a multivariate model incorporating tumor size, nuclear grade, and tumor necrosis. Patients with solitary pT1 clear cell RCC who underwent radical nephrectomy between 1970-1997 were eligible for the current study. For each of the 40 patients who died of RCC, a stratified random sample of at least 3 year-matched patients who still were alive or had died of other causes at the time of last follow-up was selected. Patient age at nephrectomy, patient gender, tumor size, nuclear grade, and tumor necrosis were evaluated, and the MIB-1 proliferative activity was assessed using digital image analysis. Univariate and multivariate Cox proportional hazards models were fit to assess the features associated with cancer specific survival. The associations between MIB-1 proliferative activity and pathologic features were assessed using the Wilcoxon rank sum test. The mean MIB-1 value for those patients who died of clear cell RCC was 6.5% compared with 3.6% for those patients who died of other causes or were still alive at the time of last follow-up. Patients whose tumor had an MIB-1 proliferative activity > o r = 5.0% were more than twice as likely to die of RCC than patients whose tumors had a MIB-1 activity < 5% (P = 0.02). However, after adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be associated significantly with cancer specific survival. There was a significant association between MIB-1 proliferative activity and tumor size, nuclear grade, and necrosis. After adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be an independent predictor of outcome in patients with pT1 clear cell RCC who were treated with radical nephrectomy. There was a significant association between MIB-1 and other well established pathologic prognostic features of pT1 clear cell RCC.

Cheville JC ，Zincke H ，Lohse CM ，Sebo TJ ，Riehle D ，Weaver AL ，Blute ML ... -  《CANCER》

Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal cell carcinoma and not surrogates for each other.

Tollefson MK ，Thompson RH ，Sheinin Y ，Lohse CM ，Cheville JC ，Leibovich BC ，Kwon ED ... -  《CANCER》

Long-term survival of patients with unilateral sporadic multifocal renal cell carcinoma according to histologic subtype compared with patients with solitary tumors after radical nephrectomy.

Dimarco DS ，Lohse CM ，Zincke H ，Cheville JC ，Blute ML ... -  《-》