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ORIGINAL ARTICLE
Year : 2009  |  Volume : 1  |  Issue : 1  |  Page : 15-17 Table of Contents     

Multicentricity and its associated clinicopathological risk factors in renal cell carcinoma


Department of Urology, Turkey Yuksek Ihtisas Education and Training Hospital, Ankara, Turkey

Date of Submission24-Dec-2008
Date of Acceptance04-Feb-2009

Correspondence Address:
B Cem Ozgur
Libya Street, 62\17 06650 Kocatepe, Ankara
Turkey
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DOI: 10.4103/0974-7796.45497

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   Abstract 

Aims : Although nephron-sparing tumor surgery (NSS) has become a routine procedure for renal tumors under certain precautions in many centers, due to the incidence of multifocality, it still remains controversial. This study examines some clinical and pathological risk factors associated with multifocal renal tumors and also factors contributing to the success or failure of NSS.
Materials and Methods: From 2000-2005, 130 patients with renal cell carcinoma (RCC) who had undergone radical nephrectomy were included in this study at one academic center. The clinicopathologic features of these cases were reviewed and categorized to identify risk factors of multifocality including age, gender, size and side of the tumor, presence of vascular invasion, Fuhrman's grade, and clinical and pathological stages.
Statistical Analysis: Data were expressed as mean. Statistical significance among groups was evaluated using Chi-square test and Fisher's exact test when appropriate. Student's t test was used for comparison of two means. Multiple logistic regression analysis was performed for risk factors of multicentricity. P < . 05 was considered to indicate statistical significance. Analyses were carried out with SPSS (version 13) software.
Results : In all, 88 men and 42 women were included with a mean (range) age of 57 years. Vascular invasion, nuclear grade, and pathological and clinical stages of the primary tumors were the significant predictors of multicentricity in the statistical analyses.
Conclusions
: These data document that multifocality of RCCs is associated with presence of vascular invasion, high grade, and advanced staged tumors. Our results support the fact that NSS is an acceptable approach to RCC without these features, as oncological safety seems less evident in such cases and should be considered for absolute indications. Future trials should be performed with adequate funding and patient-focused outcomes.

Keywords: Multifocality, nephron sparing surgery, renal cell carcinoma


How to cite this article:
Ozgur B C, Gonenc F, Yazicioglu AH. Multicentricity and its associated clinicopathological risk factors in renal cell carcinoma. Urol Ann 2009;1:15-7

How to cite this URL:
Ozgur B C, Gonenc F, Yazicioglu AH. Multicentricity and its associated clinicopathological risk factors in renal cell carcinoma. Urol Ann [serial online] 2009 [cited 2019 May 22];1:15-7. Available from: http://www.urologyannals.com/text.asp?2009/1/1/15/45497


   Introduction Top


The kidney cancer accounts for 3% of all adult malignancies, the majority of which are renal cell carcinoma (RCC). Over 12,000 deaths annually in the United States are attributed to RCC and the overall incidence of RCC has increased over the last two decades. [1] Kidney cancer is classified into types according to clinical and histological criteria and the most prevalent form, clear cell RCC, which accounts for 70% of the cases. Radical nephrectomy has been shown to be curative in localized RCC. However, in patients with a contralateral kidney disease or solitary kidney, a renal parenchymal preserving procedure, rather than total nephrectomy, is used. Recently, nephron sparing surgery (NSS) has been performed for the treatment of RCC patients with a normal contralateral kidney. While the preponderance of patients with sporadic RCC will have solitary tumors, 4-20% of patients will have multifocal RCC at the time of diagnosis. [2],[3] Compared to the pathohistological analysis of nephrectomy specimens, neither ultrasonography and color duplex sonography nor regular CT scans are able to identify multifocal lesions with acceptable sensitivity and specificity. [4] Local tumor recurrence is very likely due to the presence of occult multifocal lesions. This study was designed to investigate the incidence and associated factors of multicentricity of RCC in order to characterize these multifocal tumors, as the major disadvantage of conservative surgery is the approximate 10% risk of postoperative local tumor recurrence. [5]


   Materials and Methods Top


One hundred and thirty patients with RCC underwent radical nephrectomy in our institution between March 2000 and December 2005. There were 88 men and 42 women, with a mean age of 57 years. Tumors were staged according to UICC TNM classification (1997) and graded using Fuhrman's nuclear grade system. [6],[7] Diameter of the tumor was recorded as the greatest of the three dimensions. The farthest distance of multifocal lesions to the margin of the primary tumor was measured and recorded. After fixation in 10% formalin solution, the kidney samples were step sectioned at 3-mm intervals and examined. All tissue abnormalities were removed and stained with hematoxylin and eosin. These were examined for multifocal cancer. On each slice of the sample, parenchymal margins of the pseudocapsule were continuously examined. Statistical analysis was performed using SPSS 13.0. Data were expressed as mean and statistical significance among groups was evaluated using Chi-square test and Fisher's exact test when appropriate. Student's t test was used for comparison of two means. Multiple logistic regression analysis was performed for risk factors of multicentricity. P < 0.05 was considered statistically significant.


   Results Top


Tumor stage was pT1 in 68 specimens, pT2 in 32, pT3 in 27, and pT4 in 3, and their grades were G1 in 70 cases, G2 in 28, G3 in 22, and G4 in 10. The mean diameter of primary tumors plus or minus standard deviation (SD) was 7.33 ± 3.1 cm (range: 2.5-16). The histological pattern was clear cell in 81.5% (106/130), papillary (chromophil) in 7.7% (10/130), mixture of clear cell and granular cell in 3.8% (5/130), sarcomatoid cell in 3.8% (5/130), collecting duct carcinoma in 1.5% (2/130), and chromophobe cell type in 1.5% (2/130). Seventeen of the 130 RCC patients were diagnosed with multifocal tumors, the incidence of multicentricity being 13% (17/130) - a rate similar to that found in previous studies. These satellite tumors measured 0.2-27 mm in diameter. Ten cases had just one satellite tumor while the other seven had two or more. Among the 38 multifocal tumors, 30 (78.9%, 30/38) were <5 mm in diameter and were within 1 cm from the primary tumors. While the other eight (21.1%, 8/38) were >10 mm in diameter and distinctly separate from the primary tumors, with a distance to the primary tumor of 12-50 mm.

[Table 1] shows that the incidence of multicentricity was significantly associated with tumor size, nuclear grade, and pathological and clinical stages of the primary tumor. Multiple logistic regression analysis showed that pathological and clinical stages of the primary tumor were the significant predictors of RCC multifocality in stages T3-T4 versus T1-T2 cancers. Also, vascular invasion and histopathologically G4 types were the other significant risk predictors of the multicentricity of RCC. Other parameters, such as age, gender, and location did not significantly correlate with multifocality. Another finding in the present study was that the incidence of multicentricity in primary tumors <5 cm was not significantly lower than in tumors larger than this size following the allocation of the tumors of diameters >5 and ≤5 cm to two groups, respectively.


   Discussion Top


A significant increase in the detection of localized renal tumors has been observed with the routine use of abdominal imaging techniques. Radical nephrectomy has been shown to be curative in localized RCC. Although radical nephrectomy remains the procedure of main choice for surgically resectable lesions, NSS has become a successful alternative treatment to radical nephrectomy for RCC when a functioning renal parenchyma must be preserved, such as in patients with bilateral tumors, RCC involving a solitary functioning kidney, unilateral RCC with a normal contralateral kidney at risk for future impairment from an intercurrent disease, such as diabetes or renal calculi. NSS in carefully selected patients has resulted in favorable long-term survival and a low rate of local and systemic progression. [8],[9],[10],[11] The major disadvantage of NSS is the risk of local tumor recurrence due to undetected microscopic multifocal RCC in the remnant of the operated kidney. In patients with RCC, multifocality is detected in 4-20% of the cases after histopathological examination. Our data report a 13% rate of multifocal tumors and it was similar to prior reports. Compared to the pathohistological analysis of nephrectomy specimens, any preoperative imaging techniques are able to identify multifocal lesions with acceptable sensitivity and specificity. With the known incidence of multifocal disease, the ability to identify multifocal renal tumors preoperatively is extremely important and has been evaluated by several series. Schlichter et al. showed that preoperative imaging demonstrated multifocality in only 17% of patholgically multifocal patients prior to nephrectomy. [12] Kletscher et al. demonstrated that preoperative imaging was only able to identify 44% of multifocal tumors and multifocality is related with some pathohistological patterns. [13] The proportion of renal tumors associated with multifocal RCC has yet to be established. However, the associated factors of multicentricity of these tumors still remain unclear whether tumor location, size, pathological stage, grade, or any other factors have any influences on incidence. Kinouchi et al. reported that none of the pathologic variables examined (tumor grade, tumor stage, main tumor size, cell pattern, and vascular invasion) were found to be predictive of the presence of satellite tumors. [14] Baltaci et al. reported that only the pathological stage of the primary tumor was a significant predictor of RCC multifocality in stages T3 versus T1 and T2 cancers. [15] In our study, the incidence of multicentricity in primary tumors <5 cm was not significantly lower than that in tumors larger than this size. Our results also suggest that vascular invasion is an important risk factor for multifocality in patients with RCC. Therefore, careful and long-term follow up is mandatory in patients with RCC who have undergone NSS, especially those with vascular invasion of the primary tumor, while it is a probability having a more relaxed follow up for others. On the other hand, we found a significant increase at the risk of multifocality in stages T3-T4 and G4 tumors. These results also suggest that NSS may not be adequate in patients with advanced stages and high grades. However, one will not be able to know the grade preoperatively. Although multifocal disease is present in only a small percentage of patients with RCC, recognition of multifocality is important to ensure appropriate treatment. Close follow-up should be performed due to risk of multifocality irrespective of tumor size.

 
   References Top

1.Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, et al. Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival. Cancer 2004;101:3-27.  Back to cited text no. 1    
2.Karayiannis A, Varkarakis I, Chort M, Alivizatos G, Fragiskos S. Multifocality of renal cell tumors is a factor to consider before performing a partial nephrectomy. Anticancer Res 2002;22:3103-7.  Back to cited text no. 2    
3.Richstone L, Scherr DS, Reuter VR, Snyder ME, Rabbani F, Kattan MW, et al. Multifocal renal cortical tumors: Frequency, associated clinicopathological features and impact on survival. J Urol 2004;171:615-20.  Back to cited text no. 3    
4.Heidenreich A, Ravery V; European Society of Oncological Urology. Preoperative imaging in renal cell cancer. World J Urol 2004;22:307-15.  Back to cited text no. 4    
5.Novick AC. The role of renal-sparing surgery for renal cell carcinoma. Semin Urol 1992;10:12-5.  Back to cited text no. 5    
6.Guinan P, Sobin LH, Algaba F, Badellino F, Kameyama S, MacLennan G, et al. TNM staging of renal cell carcinoma. Cancer 1997;80:992-3.  Back to cited text no. 6    
7.Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655-63.  Back to cited text no. 7    
8.Licht MR, Novick AC, Goormastic M. Nephron-sparing surgery in incidental versus suspected renal cell carcinoma. J Urol 1994;152:39-42.  Back to cited text no. 8    
9.Lerner SE, Hawkins CA, Blute ML, Grabner A, Wollan PC, Eickholt JT, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nepron-sparing or radical surgery. J Urol 1996;155:1868-73.  Back to cited text no. 9    
10.Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: Indications, techniques and outcomes. J Urol 2001;166:6-18.  Back to cited text no. 10    
11.Ramνrez ML, Evans CP. Current management of small renal masses. Can J Urol 2007;14:39-47.  Back to cited text no. 11    
12.Schlichter A, Schubert R, Werner W, Zermann DH, Schubert J. How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery? Urol Int 2000;64:192-7.  Back to cited text no. 12    
13.Kletscher BA, Qian J, Bostwick DG, Andrews PE, Zincke H. Prospective analysis of multifocality in renal cell carcinoma: Influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy. J Urol 1995;153:904-6.  Back to cited text no. 13    
14.Kinouchi T, Mano M, Saiki S, Meguro N, Maeda O, Kuroda M, et al. Incidence rate of satellite tumors in renal cell carcinoma. Cancer 1999;86:2331-6.  Back to cited text no. 14    
15.Baltaci S, Orhan D, Soyupek S, Bedük Y, Tulunay O, Gφgüs O. Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma. J Urol 2000;164:36-9.  Back to cited text no. 15    



 
 
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