RESUMO
PURPOSE: Lymphadenectomy is a well established practice for many urological malignancies but its role in renal cell carcinoma is less clear. Our primary objective was to determine whether lymphadenectomy impacted survival in patients with fully resected, high risk renal cell carcinoma. MATERIALS AND METHODS: Patients with fully resected, high risk, nonmetastatic renal cell carcinoma were randomized to adjuvant sorafenib, sunitinib or placebo in the ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial. Lymphadenectomy was performed for cN+ disease or at surgeon discretion. Patients treated with lymphadenectomy were compared to patients in the trial who did not undergo lymphadenectomy. The primary outcome was overall survival associated with lymphadenectomy. Secondary outcomes were disease free survival, factors associated with performing lymphadenectomy and surgical complications. RESULTS: Of the 1,943 patients in ASSURE 701 (36.1%) underwent lymphadenectomy, including all resectable patients with cN+ and 30.1% of those with cN0 disease. A median of 3 lymph nodes (IQR 1-8) were removed and the rate of pN+ disease in the lymphadenectomy group was 23.4%. There was no overall survival benefit for lymphadenectomy relative to no lymphadenectomy (HR 1.14, 95% CI 0.93-1.39, p = 0.20). In patients with pN+ disease who underwent lymphadenectomy no improvement in overall or disease-free survival was observed for adjuvant therapy relative to placebo. Lymphadenectomy did not confer an increased risk of surgical complications (14.2% vs 13.4%, p = 0.63). CONCLUSIONS: The benefit of lymphadenectomy in patients undergoing surgery for high risk renal cell carcinoma remains uncertain. Future strategies to answer this question should include a prospective trial in which patients with high risk renal cell carcinoma are randomized to specific lymphadenectomy templates.
Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Excisão de Linfonodo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Risco , Sorafenibe/uso terapêutico , Sunitinibe/uso terapêutico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Resistance to imatinib mesylate is emerging as a clinical challenge in patients with metastatic gastrointestinal stromal tumors (GIST). Novel patterns of progression have been noted in a number of these patients. The objective of this study was to correlate molecular and radiologic patterns of imitinib-refractory disease with existing conventional criteria for disease progression. EXPERIMENTAL DESIGN: Patients with metastatic GIST treated with imatinib were followed with serial computed tomography/magnetic resonance imaging and [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography. Where feasible, biopsies were done to document disease progression. RESULTS: A total of 89 patients were followed for a median of 43 months. Forty-eight patients developed progressive disease. A unique "resistant clonal nodule" pattern (defined as a new enhancing nodular focus enclosed within a preexisting tumor mass) was seen in 23 of 48 patients and was thought to represent emergence of clones resistant to imatinib. Nodules were demonstrable a median of 5 months (range, 0-13 months) before objective progression defined by tumor size criteria and were the first sign of progression in 18 of 23 patients. Median survival among patients whose first progression was nodular was 35.1 months, compared with 44.6 months for patients whose first progression met Southwest Oncology Group criteria (P = 0.31). Comparative tumor biopsies were done in 10 patients at baseline and from progressing nodules. Genotypic analyses of KIT and PDGFRA kinases were done, revealing new activating kinase mutations in 80% (8 of 10) of these patients. CONCLUSION: The resistant clonal nodule is a unique pattern of disease progression seen in patients with GISTs after an initial response to imatinib and reflects the emergence of imatinib-resistant clones. Conventional tumor measurements (Southwest Oncology Group/Response Evaluation Criteria in Solid Tumors) do not detect this subtle finding. A new enhancing nodule growing within a preexisting tumor mass should be classified as a new lesion and be regarded, at least, as partial progression of GIST.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Células Clonais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Evolução Molecular , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/genética , Radiografia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Deleção de Sequência , Análise de SobrevidaRESUMO
PURPOSE: Although prostate cancer specific mortality is decreasing, there is little effect on overall mortality in this population, suggesting the possibility of an increased risk of death from nonprostate cancer related causes. Androgen deprivation therapy could adversely affect cardiovascular health. We investigated changes in lipid and glucose during androgen deprivation therapy. MATERIALS AND METHODS: We performed an exploratory analysis of pooled data from 3 prospective clinical trials aimed at achieving medical castration by comparing the gonadotropin releasing hormone antagonist abarelix, the gonadotropin releasing hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen bicalutamide. Most patients were treated in the neoadjuvant setting or because of biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were determined in 1,102 men at baseline, and on treatment days 85 and 169. In the current study men were categorized into 3 treatment groups according to the type of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate plus bicalutamide or abarelix, and statin therapy. RESULTS: Significant increases in total cholesterol, triglyceride and high density lipoprotein-cholesterol were observed in patients on leuprolide acetate or abarelix but not in patients on leuprolide acetate plus bicalutamide. Consistent changes in low density lipoprotein-cholesterol were not detected. Increased total cholesterol was usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin A1C increased from baseline to day 85 only and there were no significant changes in fasting glucose measurements. The type of androgen deprivation therapy did not affect these parameters. CONCLUSIONS: Short-term androgen deprivation therapy affects serum lipid and hemoglobin A1C independent of statin therapy.