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Background: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α (HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC)., Methods: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/-14q (VHL-WT plus HIF2α [WT/H2]), -3p/+14q (HIF1α and HIF2α [H1H2]), and -3p/-14q (HIF2α [H2])., Results: Among patients who had loss of 3p, tumors with -3p/-14q (H2) alterations were larger (P = .002), had higher grade (P = .002) and stage (P = .001), and more often were metastatic (P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with -3p/-14q (H2) had worse cancer-specific survival (P = .014), and patients who had localized disease (P = .012) and primary T1 (pT1) tumors (P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses., Conclusions: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC., (Copyright © 2013 American Cancer Society.)

Background: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS)., Methods: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated., Results: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015)., Conclusions: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway., (Copyright © 2012 American Cancer Society.)

Background: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC., Methods: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status., Results: Smokers presented more commonly with pulmonary comorbidities (P < .0001) and cardiac comorbidities (P = .014) and with a worse performance status (P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = .022), higher pathologic tumor classification (P = .037), an increased risk of bulky lymph node metastases (P = .031), and the presence of distant metastases (P < .0001), especially lung metastases (P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = .012)., Conclusions: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated., (Copyright © 2011 American Cancer Society.)

Background: The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses., Methods: In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status., Results: Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p-deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3-T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ≤4 cm in greatest dimension, 9p-deleted tumors were more likely to recur (19% vs 2%; P = .01)., Conclusions: Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment., (© 2010 American Cancer Society.)

Background: Sarcomatoid features in renal cell carcinoma may represent an aggressive subclone arising from the primary tumor. The patterns of metastases for these tumors were evaluated to determine if sarcomatoid features were retained at metastasis and whether the percentage of sarcomatoid features in the primary tumor influenced spread., Methods: All patients with sarcomatoid features found at nephrectomy with synchronous or metachronous resection of metastases were evaluated. The histology, grade, and percentage of sarcomatoid features in the primary and metastatic site were recorded. The association between percentage of sarcomatoid features, grade, histology, and pattern of metastases was evaluated., Results: Thirty-two patients were identified with sarcomatoid features and resected metastases. Fifty-two metastatic sites were evaluated. A single histologic appearance (sarcomatoid or carcinomatoid) was present in 50 of 52 sites (96%). Thirty sites (58%) demonstrated only a sarcomatoid pattern, whereas 20 (38%) contained only a carcinoma pattern. Histology and carcinoma grade did not influence metastatic pattern; however, greater percentage of sarcomatoid features was associated with the presence of distant sarcomatoid histology. A cutoff of 30% sarcomatoid features in the primary tumor was useful in predicting systemic sarcomatoid histology., Conclusions: Sarcomatoid elements are frequently observed in the metastases of primary tumors with sarcomatoid features, and these metastases generally contain a solitary pattern supporting the subclone hypothesis. However, both components can metastasize in the same patient. The percentage of sarcomatoid features influences the pattern of spread, and patients with >30% sarcomatoid features in the primary tumor frequently have distant sarcomatoid histology. This cutpoint may be helpful for inclusion criteria for future clinical trials., (Copyright 2009 American Cancer Society.)

Background: The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder., Methods: A tissue microarray was constructed that contained 724 tissue samples from 340 patients. Immunohistochemical staining was performed using the antibody MN-75, the percentage of positive cells was evaluated, and their association with tumor (T) classification, grade, and survival was assessed., Results: All normal urothelial tissue samples were negative for CAIX expression, whereas 71% of bladder cancers expressed CAIX. CAIX expression was higher in noninvasive (Ta) versus invasive (T1-T4) tumors (P < .001), in low-grade versus high-grade bladder cancer (P < .001), and in metastases versus the corresponding primary tumor (P = .032). For patients with nonmuscle invasive carcinoma who underwent transurethral resection (TUR), higher CAIX expression was associated with poorer recurrence-free survival (P = .001). In addition, for patients with T1 tumors who underwent TUR, higher CAIX expression conveyed a 6.5-fold higher risk of progression into muscle-invasive disease (P = .006). In patients who underwent cystectomy, higher CAIX expression was associated with worse overall survival (P = .003). Multivariate Cox models revealed that CAIX expression was the strongest, independent prognostic factor of recurrence-free survival (hazard ratio, 2.29; P = .001) and overall survival (hazard ratio, 1.9; P < .001)., Conclusions: CAIX was expressed differentially in noninvasive versus invasive tumors, in low-grade versus high-grade bladder cancer, and in primary tumors versus metastases. The current results indicated that CAIX is a strong predictor of recurrence, progression, and overall survival of patients with bladder cancer; and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The data suggest a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer., ((c) 2009 American Cancer Society)

Background: The management of renal cell carcinoma (RCC) is evolving toward less extirpative surgery and the use of targeted therapy. The authors set out to provide a benchmark against which emerging therapies should be measured., Methods: A prospective database including clinical and pathological variables for 1632 patients with RCC treated between 1989 and 2005 was queried. Patients were stratified using the University of California-Los Angeles Integrated Staging System (UISS) into low-, intermediate-, and high-risk groups. Disease-specific survival (DSS) was measured. Response to systemic therapy for patients with advanced disease was assessed., Results: Nephrectomy was performed in 1492 patients. Overall 5-, 10-, and 15-year DSS was 55%, 40%, and 29%. For localized disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 97% and 92%, 81% and 61%, and 62% and 41%, respectively. For metastatic disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 41% and 31%, 18% and 7%, and 8% and 0%, respectively. Patients with metastatic disease receiving immunotherapy (n=453) had complete response in 7% (median survival [MS], 120+ months), partial response in 15% (MS, 42.8 months), stable disease in 33% (MS, 38.6 months), and progressive disease in 45% (MS, 11.6 months)., Conclusions: Most patients with localized RCC do well with surgery alone, but effective adjuvant therapy is needed for patients identified as at high risk for recurrence. For advanced disease, newer targeted and potentially less toxic treatments should be at least as effective as those achieved with aggressive surgical resection and immunotherapy.

Background: Patients with renal cell carcinoma brain metastases (RCCBM) are frequently excluded from trials and to the authors' knowledge no guidelines currently exist regarding central nervous system (CNS) surveillance or treatment. The objective of the current study was to assist in the creation of treatment guidelines., Methods: Patients undergoing evaluation for RCCBM from 1989 to 2006 were identified. Their characteristics, symptoms, pathologic variables, number and size of RCCBM, CNS treatment, CNS recurrence, overall survival, and use of systemic therapy were reviewed., Results: A total of 138 patients were identified with RCCBM, of whom 92% had clear cell RCC and 95% had synchronous extracranial metastases. CNS symptoms were noted in 67% of patients. Symptomatic CNS tumors were larger (2.1 cm vs 1.3 cm; P < .001) and more frequently required a craniotomy (P < .001). The median overall survival after a diagnosis of RCCBM was 10.7 months; the 1-year, 2-year, and 5-year survival rates were 48%, 30%, and 12%, respectively. Median CNS recurrence was 9 months after RCCBM treatment. The initial number of tumors (>1 tumor) was found to be an independent predictor of CNS recurrence (hazards ratio of 3.72; P < .001). Those patients with 1 and >1 lesion had a median CNS recurrence-free survival of 13 months and 4 months, respectively (P < .001). Patients receiving interleukin-2 after CNS treatment had a response rate of 17%., Conclusions: Patients with metastatic RCC should undergo CNS screening to allow the identification of smaller lesions that are more amenable to treatment. Those patients with solitary RCCBM are less likely to develop CNS recurrence after local therapy. Selected patients with good performance status may exhibit prolonged survival and should be offered aggressive therapy.

Background: 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)., Methods: 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., Results: 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)., Conclusions: 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., ((c) 2008 American Cancer Society.)

Background: The role of nephron-sparing surgery (NSS) showed promise in patients with metastatic renal cell carcinoma (MRCC). The disease-specific survival of patients with MRCC was compared according to the type of surgery, NSS (N=45) versus radical nephrectomy (RN) (N=732), in unmatched and matched analyses., Methods: Kaplan-Meier, life tables, log-rank test, and univariate as well as multivariate Cox regression analyses addressed disease-specific survival of NSS versus RN patients. Subsequently, up to 4 RN cases were matched with each NSS case for TNM stage, Fuhrman grade, and histology. Then, disease-specific survival differences were tested with the log-rank statistic. Finally, the sample size necessary to achieve 80% power in survival analyses between the 2 groups (NSS vs RN) was calculated., Results: Of 45 NSS cases, 38 were matched with 99 of 732 RN cases. First, in multivariate unmatched analyses RN predisposes to 1.7-fold higher RCC-specific mortality rate; second, in matched analyses RN predisposes to 1.5-fold higher RCC-specific mortality rate; and third, both analyses failed to demonstrate statistically significant differences. Based on these findings it could be postulated that until further data become available, NSS does not appear to undermine RCC-specific survival in carefully selected patients with MRCC. The power analyses demonstrated that at least 146, 48, and 76 observations per arm are necessary at 1, 2, and 3 years, respectively, to confirm survival equivalence., Conclusions: Although the data were limited in size and completeness, they may indicate that RCC-specific survival may not be undermined if NSS is performed in properly selected cases., (Copyright (c) 2007 American Cancer Society.)

Background: The mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development. The goal of the study was to evaluate the potential and limitations of targeting the mTOR pathway in renal cell carcinoma (RCC)., Methods: Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6 was performed on a tissue microarray constructed from paraffin-embedded specimens from 375 patients treated by nephrectomy for RCC. The expression was associated with pathological parameters and survival., Results: The mTOR pathway was more significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor prognostic features. PS6 and PTEN showed the strongest associations with pathological parameters. Survival tree analysis regarding expression of cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff values for stratification, with corresponding P-values of .03, .001, .02, .005, and <.0001, respectively. Interestingly, high nuclear pAkt expression was associated with a favorable prognosis, whereas high cytoplasmic pAkt expression was associated with a poor prognosis. In multivariate Cox regression analysis, ECOG PS, T classification, N classification, M classification, cytoplasmic Akt, nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS., Conclusions: Components of the mTOR pathway are significantly associated with pathological features and survival. Not all RCC tumor types seem to be equally amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as surrogate parameters for patient selection and predicting prognosis. Patients with a highly activated mTOR pathway should benefit most from this therapy. External validation of our results is recommended., ((c) 2007 American Cancer Society.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright 2005 American Cancer Society.)

Background: The objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy., Methods: The medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid-stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival., Results: The median follow-up was 3.2 years (range, 0.2-9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high-risk group had 1% survival at 1 year and no survivors at 3 years., Conclusions: In patients with metastatic RCC who were treated with nephrectomy and IL-2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials., (Copyright 2003 American Cancer Society.)

Background: The current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC)., Methods: A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population., Results: Two hundred thirty-six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. N0M1 patients were more likely to achieve an objective response to systemic immunotherapy compared with N+M1 patients (P = 0.01). N+M1 patients overall had worse short-term and long-term survival compared with N0M1 patients, with a median survival of 10.5 months compared with 20.4 months, respectively. The median survival of N0M1 patients was improved to 28 months in those who received adjunctive immunotherapy (P = 0.0008), whereas the median survival of patients with N+M1 disease was the same in those treated with and those treated without adjunctive immunotherapy (P = 0.18)., Conclusions: Even in the modern era of systemic immunotherapy, the presence of regional lymphadenopathy exerts a detrimental effect on the survival of patients with metastatic RCC. Lymph node status is a strong predictor of the failure to achieve either an objective immunotherapy response or an improvement in survival when immunotherapy is given as an adjunctive treatment after cytoreductive nephrectomy. However, in multivariate analysis, including both clinical and pathologic variables, lymph node status was found to have less of an impact on survival than primary tumor stage and grade and patient performance status., (Copyright 2003 American Cancer Society.)