Japanese Journal of Clinical Oncology 32:291-295 (2002)
© 2002 Foundation for Promotion of Cancer Research
Clinical Outcome of Surgical Resection for Renal Cell Carcinoma
Department of Urology, Kobe University School of Medicine, Kobe, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Purpose: To evaluate prognostic factors for patients with renal cell carcinoma (RCC) who had undergone surgical resection.
Patients and methods: We analyzed data from 371 patients with RCC who had undergone surgical resection. Prognostic factors were identified from clinical and pathological data using univariate and multivariate analysis.
Results: When we analyzed all patients including lymph node metastasis, multivariate analysis showed that only pN factor was an independent prognostic factor. We then analyzed 359 patients without lymph node metastasis, and the presence of symptoms, pT, grade, IFN and venous involvement were considered significant. However, pT (pT1 vs pT2–4), tumor grade and presence of symptom were judged to be independent prognostic factors by multivariate analysis. When the patients were stratified according to the tumor size (2.5, 4, 7 cm), a significant difference in disease specific survival was found by 4 and 7 cm, but not by 2.5 cm.
Conclusions: The current TNM staging accurately predicts patient survival. Tumor grade is also an important prognostic factor for patients with RCC.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Although renal cell carcinoma (RCC) is a widespread type of urogenital malignancy, treatment has not been significantly improved. Although partial nephrectomy is frequently performed (1), radical nephrectomy seems to be the gold standard for treating localized renal cell carcinoma. Many investigators have reported the prognostic factors for renal cell carcinoma (2–16). Although the conclusions drawn from these investigations are similar, some discrepancies are apparent. Most of them considered tumor stage as an important prognostic factor, yet how to define tumor stage is critical. The most recent TNM staging was defined in 1997 (17), in which the boundary in tumor size between pT1 and pT2 was change from 2.5 to 7 cm. In RCC confined to organs, the size of the tumor seems to be an important factor (9,16,18). Venous involvement (13–15) and tumor grade (7) are also considered independent prognostic factors by some investigators. We therefore analyzed clinical outcomes of radical nephrectomy to determine prognostic factors for patients with renal cell carcinoma at our institute and related hospitals.
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PATIENTS AND METHODS |
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Patients
Between 1987 and 2001, 371 patients (256 male, 115 female; age range, 21–88 years; mean, 60.7 years) without distant metastasis underwent curative resection for renal cell carcinoma at Kobe University Hospital and related institutions. Patients with known distant metastasis were excluded. Tumors were located on the right in 182 patients and on the left in 189 patients. Radical nephrectomy and nephron-sparing surgery were performed in 355 and 16 patients, respectively. Basically, ipsilateral lymph node dissection was performed, briefly, the left side of the aorta in left RCC and the right side of the vena cava in right RCC. After surgical resection, 222 patients received interferon (IFN) as adjuvant therapy. The mean follow-up period was 44 months, ranging from 5 to 234 months.
Pathological Examination
Pathological staging was based on microscopic examination. TNM staging was based on the 1997 UICC classification (17). Tumors were graded by the WHO criteria. The mode of tumor infiltration was classified as expansive (INF 
), intermediate (INF ß) or diffuse (INF 
). The presence of venous involvement was also evaluated. The patients were divided into two groups according to prognostic factors.
Statistical Analysis
Ten potential prognostic factors were evaluated. Age, gender, location of tumor (right or left) presence of symptoms and presence of adjuvant therapy were considered as potential clinical prognostic factors. Tumor stage (pT), presence of lymph node involvement (pN), tumor grade, tumor infiltration (TI) and venous involvement were examined as potential pathological prognostic factors. Statistical analysis of survival was calculated by the Kaplan–Meier method and differences were evaluated using a log-rank test. Differences with P < 0.05 were considered significant. Significant factors were analyzed by the multivariate Cox’s proportional hazards test. Differences with P < 0.05 were considered significant.
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RESULTS |
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Overall Survival
The overall values of cause-specific survival at 5 and 10 years were 89.5 and 84.8, respectively. Among these patients, 25 died of RCC. Among 10 potential prognostic factors, age, the presence of symptoms, pT, pN, grade, IFN and venous involvement were considered as significant prognostic factors by univariate analysis. The factors considered significant according to the univariate analysis (presence of symptoms, pT, pN, grade, IFN and venous involvement) were used as variables for the multivariate logistic analysis using Cox’s proportional hazards test. Only pN was considered as an independent prognostic factor. This result indicates that the presence of lymph node metastasis had such a great influence that we had to re-analyze the patients without lymph node metastasis.
T1–4N0M0 Patients
Since lymph node involvement implies systemic prevalence, we re-evaluated these factors in 359 patients without lymph node metastasis. Patients’ characteristics are shown in Table 1 and Table 2 gives the results of the univariate analysis. The presence of symptoms, pT, grade, IFN and venous involvement were considered significant. The differences between pT1 vs pT2–4 and between pT1–2 vs pT3–4 were also significant. This is why multivariate analysis was performed twice according to each subgroup (pT1 vs pT2–4, pT1–2 vs pT3–4). When the patients were divided into pT1 vs pT2–4 groups, pT was considered significant (Table 3). However, the presence of symptoms and tumor grade were considered as an independent prognostic factor when the patients were divided into pT1–2 vs pT3–4 groups (Table 4).
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Influence of Tumor Size on Survival Rate
The tumor size of renal cell carcinoma is a very important prognostic factor. The classification of T category was changed in 1997. In the TNM classification in 1987, the boundary of T1 and T2 was 2.5 cm. In 1997, the new boundary of T1 and T2 was 7 cm and T was subdivided into T1a (<4 cm) and T1b (>4 cm). We analyzed our patients using these criteria and searched which classification was rational. Table 5 shows the results of univariate analysis using different stratifications. When the patients were stratified according to the tumor size (2.5, 4, 7 cm), a significant difference in disease specific survival was found by 4 and 7 cm, but not by 2.5 cm.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Since no modality other than surgical resection is effective for treating RCC, it is important to evaluate the clinical outcomes of surgery and to assess prognostic factors obtained from surgical specimens. Many efforts have been made to identify prognostic factors with which to determine the prognosis of patients with RCC who undergo surgical resection (2–16). Most of these reports present several independent prognostic factors derived from multivariate analyses using Cox’s proportional hazard model. Although the conclusions of these reports differ somewhat, tumor stage, nodal involvement, presence of metastasis, tumor grade, vascular involvement and tumor size are commonly considered independent prognostic factors. Preoperative serum levels of acute phase reactants such as erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were also considered prognostic factors. Some investigators sought more powerful prognostic factors such as proliferating cell nuclear antigen (PCNA) expression (3), DNA ploidy (10) and mitotic frequency (5).
Tumor stage (pT) seems to be the most reliable prognostic factor. However, the definition of pT remains controversial. The latest TNM staging was defined in 1997 (17). The main modification of the 1997 TNM staging was the definition of pT1 and pT2. The boundary of tumor size between pT1 and pT2 was 2.5 cm prior to 1997 and 7 cm thereafter. In addition, pT1 was divided into pT1a and pT1b subgroups. The boundary of pT1a and pT1b is a tumor size of 4 cm. Hence the tumor size of RCC is considered a crucial prognostic factor. In fact, Bell reported an association between tumor size and prognosis for patients with RCC in 1938 (2). He noted that only one of 38 cortical tumors smaller than 3.0 cm developed metastases compared with 70 of 106 tumors larger than 3.0 cm. Many investigators supported the notion that tumor size is closely related to prognosis. However, the cut-off value of tumor size is difficult to determine. Javidan et al. (18) investigated which TNM staging (1987 vs 1997) was more closely correlated with prognosis, that is, whether the boundary between pT1 and pT2 should be 2.5 or 7 cm. He concluded that both classifications were strong predictors of survival in univariate and multivariate analyses and essentially equivalent in the ability to predict patient outcome. However, a comparison of survival curves in Kaplan–Meier life tables revealed a better separation of survival for T1N0M0 and T2N0M0 patients under the 1997 TNM classification. Zisman et al. studied the 11 potential cut off points between 1 and 10 cm (16). They concluded that 4.5 cm was most predictive of patient survival (hazards ratio 4.99, P = 0.0001). However, Nativ et al. found no differences in progression rate or survival between tumor sizes smaller and larger than 5 cm (12). In our study, multivariate analysis revealed a significant difference in the cause-specific survival rate between pT1 and pT2–4. Moreover, we compared disease specific survival of the patients according to the tumor size in 2.5, 4 and 7 cm. By univariate analysis, we found a significant difference in cause-specific survival when the tumor size was stratified in 4 and 7 cm, but not in 2.5 cm. This result strongly supported the justification of TNM staging in 1997.
Lymph node involvement is also considered an important prognostic factor (7,13). In fact, when we analyzed the patients including lymph node metastasis, multivariate analysis showed that only pN factor was an independent prognostic factor. Since the patients with lymph node metastasis should be considered as having systemic disease, many investigations excluded patients with lymph node metastasis. Therefore, we re-analyzed the patients excluding lymph node metastasis.
We found that tumor grade was another independent prognostic factor. Since we followed the classification of tumor grade according to the ‘General Rules for Clinical and Pathological Studies on Renal Cell Carcinoma’, the worst tumor grade was 3 (19). Few patients generally progress to grade 3 RCC, so most investigators stratified tumor grade as 1 vs 2 + 3 (11,14). However, the prognosis of grade 3 tumor was extremely poor. This is why we stratified tumor grade as 1 + 2 vs 3. We believe that tumor grade was an independent prognostic factor in our study because of this stratification. Inomiya et al. (7) also compared grades 1 and 3 and showed by multivariate analysis that tumor grade is an independent prognostic factor.
Some investigators sought more powerful prognostic factors such as proliferating cell nuclear antigen (PCNA) expression (3), DNA ploidy (10) and mitotic frequency (5). However, these parameters are still experimental and whether they will be of practical value in the routine clinical environment remains to be determined.
In conclusion, TNM staging in 1997 is appropriate for predicting the prognosis of RCC patients. When tumor grade was stratified into grade 1 + 2 vs 3, grade 3 can be an independent prognostic factor according to multivariate analysis.
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FOOTNOTES |
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+ For reprints and all correspondence: Isao Hara, Department of Urology, Kobe University School of Medicine, 7–5–1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Email: hara@med.kobe-u.ac.jp
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Received January 8, 2002; accepted May 14, 2002
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