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and stage at presentation. Lastly, the underlyingmechanism behind the differences we observed ingrade and histologic subtype between the genderscannot be further explained with the use of this typeof data set, which represent an additional limitation.
5. Conclusions
Population-based data from the SEER RCC databasesuggest that women present at a slightly olderage than men with tumors that are smaller, lowerstage, and lower grade. Although overall survival issuperior in women, the cancer-specific survivalwhen adjusted for stage and grade is similar to men.
Gender differences in RCC biology and epidemiol-ogy are incompletely understood. Further researchis indicated to define the fundamental basis of theseobserved differences.
Conflicts of interest
Inderbir S. Gill is a consultant and stockholder forHansen Medical, Mountain View, CA, USA.
Source of funding: None.
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Editorial Comment on: Impact of Gender inRenal Cell Carcinoma: An Analysis of theSEER DatabaseMasaru MuraiDepartment of Urology, Keio University School ofMedicine, International Goodwill Hospital,Tokyo, [email protected]
The incidence of renal cell carcinoma (RCC)has been increasing worldwide. Men have twicethe incidence of developing RCC as women. Aronet al. elucidated the differences between the
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genders in terms of cancer progression. Men tendto present with a larger size tumor, a higher stageand a higher grade RCC than women. In contrast,women tend to demonstrate smaller and lowergrade tumors. Men also have a higher incidenceof regional or metastatic spread [1]. There are fewreports of a male survival advantage [2]. Thesedifferences suggest that the hormonal status, i.e.estrogen has an impact on the course of cancer.
The clinical use of anti-angiogenesis agents forthe treatment of metastatic RCC suggest that RCCgrowth is supported by endothelial cells. Macro-phages or fibroblasts might also support the cancer
growth or metastatic spread. In these processes,growth factors including vascular endothelialfactor (VEGF) or inflammatory cytokines includinginterleukin-6, -8 might play a role. Adipocytokinesmay also play a role because obesity is one of theclassic risk factors along with smoking and hyper-tension. Gender differences are prominent in someadipocytokines [3]. Furthermore, recent reportsdescribe that leptin, an adipocytokine, is relatedto invasiveness and the progression of RCC [4].
A recent report has shown the IL-6 production tohave a gender disparity in a chemically inducedanimal model of liver cancer [5]. The hormonalenvironment may link the cytokines or growthfactors related to cancer progression. In themicroenviroment where renal cancer cells prolif-erate, these cancer cells may be supported byendothelial cells, macrophages, fibroblasts andadipocytes via growth factors, inflammatory cyto-kines or adipocytokines. To elucidate the under-lying mechanism of gender differences in RCC,further investigations of the microenviromentmaintained by the cytokines are thus called for.
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DOI: 10.1016/j.eururo.2007.12.002
DOI of original article: 10.1016/j.eururo.2007.12.001
Editorial Comment on: Impact of Gender inRenal Cell Carcinoma: An Analysis of theSEER DatabaseJean-Jacques PatardDepartment of Urology, Rennes University Hospital,Rennes, [email protected]
This paper provides interesting informationbecause it deals with an issue that has been poorlyexplored so far. However, when we read carefullythe results that are presented here by Aron et al, itis obvious that important biologic issues could behidden just behind clinical and pathologic findings[1]. Data presented in this manuscript have beenextracted from the National Cancer Institute Sur-veillance, Epidemiology and End Results Program(SEER) database and >35,000 records have beenexamined. The authors demonstrate that menpresented with larger, higher stage, higher graderenal tumors than women. Interestingly, althoughgender was clearly associated with better survival inunivariate analysis, it was not retained as anindependent prognostic variable when other majorclinical or pathologic renal cell carcinoma prognos-tic variables were introduced into the model.
In our multi-institutional database including>10,000 observations from 24 academic centers wefound basically the same trends. Female genderwas associated with lower T stage, lower Fuhrmangrades, and less propensity for tumors to exhibitperinephritic fat invasion (19.4% vs 23.2%) or topresent with distant metastases (13.3% vs. 16.6%,p = 0.0001). In our series, tumor size, N stage, andadrenal, renal vein, or inferior vena cava invasionrates did not appear to be significantly differentaccording to the male-to-female ratio. However,similar to the results reported by Aron et al, femalegender was associated with a more favorableoutcome than male gender for either overallsurvival (median not reached vs. 210 mo,p = 0.0001) or cancer-specific survival (160 vs. 130mo, p = 0.0001). Again, gender was not retained asan independent prognostic variable for the entirecohort. The biologic enigma behind these data isthat we also found that women were more likely tohave tumors with clear-cell histologic subtype (86%vs. 83.8%, p = 0.0001) and were more likely topresent with symptoms at diagnosis (46.4% vs.43.3%, p = 0.0001) or with poor performance status(Eastern Cooperative Oncology Group �1; 33.1% vs30.0%, p = 0.0001). These data together should
e u r o p e a n u r o l o g y 5 4 ( 2 0 0 8 ) 1 3 3 – 1 4 2 141
