UROLOGICAL ONCOLOGY Prognostic Significance of Body Mass Index and Other Tumor and Patient Characteristics in Non- Metastatic Renal Cell Carcinoma Vusal Ahmedov, Fuat Kızılay*, İbrahim Cüreklibatır Purpose: In this retrospective study, we aimed to investigate the prognostic effect of body mass index (BMI) in localized renal cell carcinoma (RCC) cases who underwent surgical treatment. Furthermore, the assessment of various patient and tumor characteristics and surgical methods on survival has been identified as additional targets. Materials and Methods: Three hundred and eighty patients with localised, non-metastatic, unilateral RCC who underwent radical or partial nephrectomy in our clinic between January 2007 and December 2016 were enrolled in this study. Age, gender, height, weight, BMI, operation type and method, pathology results and tumor stage of the patients were recorded. Patients were divided into 3 groups according to body mass index (BMI): Normal weight (< 25 kg/m2), overweight (25-30 kg/m2) and obese (> 30 kg/m2) as groups 1, 2 and 3, respectively. We analyzed the relation between the BMI, gender, smoking, hypertension, type and method of surgical treatment, histologic subtype, tumor stage, estimated glomerular filtration rate (eGFR) and cancer-specific (CSS) and recurrence free survival (RFS). All data analysis was performed using SPSS® Statistical Software for Windows (Version 13.0) and a P value less than 0.05 was considered to be significant. Results: The effect of BMI on both CSS and RFS was statistically significant (P < .001). There was also a signifi- cant relation between smoking, operation type (partial/radical), eGFR and tumor stage and CSS and RFS. Conclusion: Our findings show that overweight and obese RCC patients according to the BMI have a more fa- vorable prognosis. Multicenter, prospective studies with more cases and longer oncological follow-up period are needed to support these findings. Keywords: body mass index; prognosis; renal cell carcinoma; recurrence; survival. INTRODUCTION Renal cell carcinoma (RCC) accounts for 2-3 % of all cancers(1). The incidence of RCC increases around the world in the last decades and it has been re- ported that 20-40 % of patients will develop local recur- rence or distant metastases after localized RCC treat- ment with partial or radical nephrectomy(2). RCC is a very heterogeneous and complex disease with a widely varying prognosis. In cases of kidney cancer, it is very important to be able to predict the prognosis and the response to selected treatments prior to disease management. However, some problems are anticipated in predicting the prognosis of RCC. The main causes of these are as follows; natural course of kidney can- cer is highly complicated and significantly differs be- tween the patients, many defined prognostic variables are present and these variables interact with each other. Factors affecting prognosis of RCC are tumor-related (anatomical and histological features) and patient-relat- ed factors (clinical findings, symptoms, general health status, laboratory findings, and molecular factors). At present, the pathologic stage (pT), lymph node status (pN) and histologic grade of the tumor represent the most important prognostic variables. However, some other characteristics of the patient and the tumor have been shown to be associated with renal cancer out- comes. Recently, several systems have been designed Ege University School of Medicine, Urology Department, Izmir, Turkey. *Correspondence: Department of Urology, Ege University School of Medicine, Izmir, Turkey. Tel: +90 532 5800685. Fax: +90 232 3746552. E-mail: fuatkizilay@gmail.com. Received July 2017 & Accepted December 2017 by combining various prognostic factors to obtain a powerful and important prognostic model for RCC(3-5). Many epidemiological studies have shown that obesity and family history are important risk factors for RCC(6- 8). Although obesity is a well-known risk factor for RCC, there are articles reporting that obesity improves or at least does not worsen the disease prognosis(9,10). In this study, we aimed to analyze the prognostic effect of body mass index (BMI) in our localized RCC cohort managed with surgical treatment. We also evaluated the effect of gender, smoking, hypertension, surgical treatment type and method, histologic tumor subtype, estimated glomerular filtration rate (eGFR) and tumor stage on cancer-specific (CSS) and recurrence free sur- vival (RFS). PATIENTS AND METHODS Patient selection The study was initiated after the local ethics committee approval. Three hundred and eighty patients with lo- calised, non-metastatic, unilateral renal cell carcinoma who underwent radical or partial nephrectomy in our clinic between January 2007 and December 2016 were enrolled in this retrospective study. These were consec- utive cases and all of them were operated in the same clinic. Patients with metastatic renal tumor who under- went radical nephrectomy (n = 14) and patients with bi- Urological Oncology 96 Vol 15 No 03 May-June 2018 97 lateral renal tumor who underwent partial nephrectomy (n = 4) were excluded from the study. Seventy-seven patients with papillary histology were excluded from the study since it may be hereditary. Also, patients whose pathologic report revealed end-stage angiomy- olipoma, oncocytoma and unclassified carcinoma were not included in the study (n = 8), 6 patients had missing data and 7 patients were lost to follow-up (Figure 1). Database and Patient Groups Age, gender, height, weight, BMI, operation type and method, pathology results and tumor stage of the pa- tients were recorded. Tumor staging was established ac- cording to 2010 tumor, node, metastasis classification (11). The results of preoperative and postoperative lab- oratory examinations such as chest X-ray, abdominal ultrasonography, thorax and abdominal tomography, magnetic resonance imaging, brain tomography and bone scintigraphy were reviewed from patient files. The weight and height of the patients were recorded at the first visit. Patients were divided into 3 groups according to BMI: Normal weight (< 25 kg/m2), over- weight (25-30 kg/m2) and obese (> 30 kg/m2) as groups 1, 2 and 3, respectively. The abbreviated Modified Diet and Renal Disease equation was used to measure eGFR using the last serum creatinine before surgery(12). Patients were classified as having a baseline eGFR of above 60, between 45-60 and less than 45 mL/min per 1.73 m2. Recurrences detected at the site of the surgery in patients who underwent radical nephrectomy and re- currences detected in the residue kidney in patients who underwent partial nephrectomy were accepted as local. In cases of partial nephrectomy, recurrences at different locations in the same kidney were also accepted as lo- cal. Elsewhere in the body, masses that are associated with kidney tumors were considered as distant recur- rences. All recurrences were detected by cross-sectional imaging in the postoperative follow-up period. Patients were stratified according to the American Society of Anesthesiologists (ASA) score. Preoperative preparation Before surgery, all patients underwent physical exam- ination, routine blood and urine examinations, two-di- mensional chest radiography, abdominal ultrasonog- raphy and tomography. Preoperative imaging of the patients did not reveal any regional (retroperitoneal ad- enopathy) or distant metastasis. Where necessary, diag- nostic tests such as Doppler ultrasonography, magnetic resonance imaging and bone scintigraphy were added. Written, informed consent of the patients was obtained before surgery. All patients underwent detailed anesthe- sia examination before the operation. Surgical treatment and follow-up Patients underwent radical or partial nephrectomy with open or laparoscopic methods under general anesthe- sia. Tumor size (4 cm) was typically the determining factor in the selection of partial or radical nephrectomy. However, this criterion was not strictly determinative, Table 1. Proposed surveillance schedule following treatment for RCC, taking into account patient risk profile and treatment efficacy. Risk profile Follow-upa 6 12 24 36 48 60 > 60 Low US CT US CT US CT Discharge Intermediate CT CT CT US CT CT CT once every 2 years High CT CT CT CT CT CT CT once every 2 years a Numbers indicate the month. CT: computed tomography of chest and abdomen, alternatively use MRI; US: ultrasound of abdomen, kidneys and renal bed. Figure 1. Study flow chart aRenal cell carcinoma, bBody mass index Prognostic factors in RCC-Ahmedov et al. and surgical decision was made according to factors such as surgeon preference and experience, tumor lo- cation, size and patient comorbidities. Patients were divided into groups according to type and method of surgery, and the difference between survival rates was examined. The protocol recommended by the Guide- lines of the European Urological Association(13) was used to follow-up the patients (Table 1). Outcome measures Our primary outcome measurement was the relation between the BMI and survival rates and our secondary outcome measurement was the relation between gender, smoking, hypertension, type and method of surgical treatment, histologic subtype, tumor stage and survival rates. We calculated the CSS ratios by calculating the percentage of patients who did not die from the RCC in the follow-up period. Patients who died from caus- es other than the disease being studied are not counted in this measurement. The length of time after primary treatment for RCC ends that the patient survives with- out any signs or symptoms of cancer was calculated as RFS. Statistical analysis The Kolmogorov-Smirnov test was used to determine whether the variables met the normal distribution. Normal distribution-matching data were shown by mean and standard deviation while the non-matching data were shown by median and between the quar- ters. The student test was used to compare the varia- bles and survival analysis was performed by univariate and multivariate Cox proportional hazards model and Kaplan-Meier method. All data analysis was performed using SPSS® Statistical Software for Windows (Version 13.0). P value less than 0.05 was considered to be sig- nificant. RESULTS Two hundred and forty-one (63.4 %) of the 380 pa- tients were male and 139 (36.6 %) were female. The vast majority of patients (306, 80.5%) were in the ASA I-II group. Sixty-two patients (16.3%) were in ASA III group and 12 patients (3.1%) were in ASA IV group. The mean follow-up period of the patients was 62.28 ± 1.16 months (0-98). According to the follow-up proto- col proposed in Table 1, 72 patients were followed up at 6 months, 68 at 12 months, 62 at 24 months, 58 at 36 months, 51 at 48 months, 42 at 60 months and 27 at > 60 months. Seven patients who did not comply with the protocol were excluded from the follow-up. When BMI Table 2. Patient and operation characteristics Variables Number (n) Ratio (%) Mean(±SD) Sex Male 241 63.4 Female 139 36.6 Age (year) Male 61.6 ± 10.8 Female 39.2 ± 12.3 BMIa (kg / m2) 25.6 ± 2.9 Height (cm) 162.8 Body weight (kg) 75.4 Smoking Yes 191 50.2 Amount (cigarettes/day) 1-10 55 10-20 61 > 20 75 Duration (years) 1-10 60 11-20 92 No 189 49.8 Hypertension Yes 27 7.1 No 353 92.9 Operation type Partial nephrectomy 85 22.3 Radical nephrectomy 295 77.7 Operation method Laparoscopy 74 19.4 Open 306 80.6 eGFRb < 45 88 23.1 45-60 143 37.6 > 60 149 39.3 Tumor characteristics Stage T1a 138 36.3 T1b 128 33.6 T2a 38 10.0 T2b 6 1.57 T3a 70 18.4 Localization Upper pole 115 30.2 Middle pole 128 33.6 Lower pole 122 32.1 Hilar 15 3.94 Side Right 194 51.1 Left 186 48.9 Histological subtypes Clear cell 316 83.1 Chromophobe 59 15.5 Mucinous tubular spindle cell 4 1.05 Multilocular cystic 1 0.26 aBody mass index bEstimated glomerular filtration rate (mL/min per 1.73 m2) Prognostic factors in RCC-Ahmedov et al. Urological Oncology 98 Vol 15 No 03 May-June 2018 99 and histologic subtype relation were examined, clear cell pathology was higher in the first group compared to the other two groups, but it was not statistically sig- nificant (P = .0822). The mean tumor size was 5.3 cm (IQR = 3.92). The mean follow-up period of the patients was 50.8 ± 18.1 months. Surgical margin positivity was confirmed in 33 patients (8.68%). Local or distant recurrence was ob- served in 82 of 380 patients (21.57%). The mean time to recurrence was 30.2 ± 21.4 months. Eighty-two of the patients (21.57%) died in follow-up. The mean time to exitus was 29.6 ± 12.4 months. Demographic and operation data and tumor characteristics are shown in Table 2. Cancer-specific survival The mean cancer-specific survival time of the patients after diagnosis was 73.5 ± 1.2 months. When the rela- tion between BMI and survival time was analyzed, the mean survival time in group 1 was 58.6 ± 2.8 months, 82.5 ± 1.5 months in group 2 and 84.6 ± 1.4 months in group 3 (P < .001) (Figure 2). The mean survival time was 64.6±2.4 months in smokers and 84.2 ± 1.2 months in non-smokers (P < .001). The number of cigarettes smoked per day and the duration of smoking also sig- nificantly affected survival rates (P < .001). Mean sur- vival time was 88.6 ± 1.1 months in patients undergoing partial nephrectomy and 73.7 ± 1.8 months in patients undergoing radical nephrectomy (P = .001). Multiloc- ular cystic and mucinous tubular spindle cell carcino- ma tumors were excluded from the analysis due to low number of cases. Mean survival time was 75.6 ± 2.0 months in patients with clear cell pathology and 82.2 ± 3.6 months in patients with chromophobe pathology (P = .442). A statistically significant difference was also observed between tumor stage and survival time (P < .001). We found that preoperative eGFR significantly affected the CSS (P < .001). Because tumor stage is a very important determinant of cancer-specific survival, CSS analysis according to the stage is shown in Figure 3. Recurrence-free survival The mean recurrence-free survival time of the patients was 74.8 ± 1.8 months. When the relation between BMI and recurrence-free survival was examined, the mean recurrence-free survival time was 58.2 ± 3.4 months in group 1, 77.3 ± 2.5 months in group 2 and 82.8±1.9 months in group 3 (P < .001) (Figure 4). Mean recur- rence-free survival time was 69.8 ± 2.6 months in smok- ers and 89.6 ± 1.8 months in non-smokers (P = .001). The number of cigarettes smoked and the smoking du- ration significantly affected RFS (P < .001). The mean recurrence-free survival time was 88.4 ± 1.3 months in patients undergoing partial nephrectomy and 68.4 ± 2.2 months in patients undergoing radical nephrectomy (P Table 3. Effects of patient and tumor characteristics on survival. Variables Number (n) Number of Number of Mean cancer-specific Mean recurrence-free 95% CIa 95% CIb P valuea P valueb deaths (n) recurrences (n) survival (month) survival (month) local distant BMIc groups 1 126 48 32 10 58.6 58.2 51.8–66.9 51.6–67.8 < 001 < 001 2 135 11 11 6 82.5 77.3 80.1–88.2 72.3–83.6 3 119 7 7 2 84.6 82.8 82.1–89.7 79.6–89.7 Sex Male 241 41 22 16 74.7 72.9 71.8–81.4 68.6–78.8 0.540 0.648 Female 139 25 22 8 74.2 73.8 70.2–81.3 67.8–80.4 Smoking Yes 191 49 31 13 64.6 69.8 62.1-74.0 61.2-73.4 Amount (cigarettes/ day) 1-10 72 8 5 2 78.3 74.3 68.2-78.5 10-20 61 13 7 4 62.8 64.2 71.5-80.5 60.4-68.9 > 20 58 28 20 6 44.6 52.2 57.8-64.1 48.4-56.8 < 001 < 001 Duration (years) 121 15 8 5 67.5 70.2 65.2-70.6 65.5-74.1 1-10 70 34 22 9 42.2 62.1 39.2-46.4 58.2-65.4 11-20 No 189 17 17 7 84.2 89.6 80.1–88.2 78.7–91.8 Hypertension Yes 27 12 23 8 62.6 56.2 56.7–71.6 49.6–64.4 0.488 0.089 No 353 54 22 15 74.4 74.6 72.7–81.4 70.8–79.2 Operation type Partial 85 8 6 3 88.6 88.4 83.1–91.6 82.8–91.6 < 001 < 001 Radical 295 58 44 15 73.7 68.4 67.2–77.1 63.5–72.2 Operation method Open 306 38 24 9 76.7 75.2 72.1–81.3 70.7–79.5 0.720 0.680 Laparoscopic 74 28 23 12 76.1 76.8 69.2–81.9 68.3–82.8 Histological Clear cell 316 42 24 7 75.6 74.7 71.1–79.8 69.8–78.8 0.442 0.584 subtypes Chromophobe 59 24 23 14 82.2 79.6 76.7–92.6 73.8–92.1 Stage T1a 138 3 5 2 88.1 87.9 82.2–90.2 83.4–90.6 < 001 < 001 T1b 128 8 6 3 77.8 76.4 71.8–82.5 71.8–82.2 T2a 38 12 8 3 71.3 71.6 66.5–80.1 69.1–81.3 T2b 6 16 10 5 58.5 56.4 48.9–66.6 46.1–62.8 T3a 70 27 18 8 48.9 46.1 42.8–63.6 38.4–54.3 eGFRd < 45 88 37 25 7 45.8 52.9 38.8-48.1 50.8-54.3 < 001 < 001 45-60 143 23 17 5 59.6 61.8 52.2-61.4 59.7-63.3 > 60 149 6 11 3 82.1 84.3 78.3-86.8 82.8-86.5 aConfidence interval and P values for cancer-specific survival bConfidence interval and P values for recurrence-free survival cBody mass index dEstimated glomerular filtration rate (mL/min per 1.73 m2) Prognostic factors in RCC-Ahmedov et al. < .001). There was a statistically significant negative association between tumor stage and recurrence free survival (P < .001). Preoperative eGFR significantly affects RFS similarly to CSS (P < .001). The relation between patient and tumor characteristics and CSS and RFS is shown in Table 3. Univariate and multivariate analyzes indicating the relationship of variables with survival are presented in Table 4. DISCUSSION Nowadays, obesity is a very important public health problem and it is reported that in the United States more than one-third of adults and 17 % of youth are obese (14). Obesity is indicated to be an important risk factor for sporadic RCC in the European Urological Associa- tion (EAU) Guideline and the risk of RCC is reported to be 3.6 times more in obese patients compared with the general population(15). As already mentioned, the in- cidence of RCC is increasing every year worldwide. It is quite significant that this incidence shows parallelism with the increase in the incidence of obesity. Several community-based case-controlled epidemi- ological and clinical, prospective studies have been conducted to establish the relationship between obe- sity and renal cancer. Many epidemiological studies have addressed the relationship between obesity and renal cancer. The upregulation of leptin and downreg- ulation of adiponectin pathways has largely explained the pathogenesis of RCC(16). Obese people have more health problems than normal weight people, so they are subjected to more frequent health controls and this may be the reason of more frequent occurrence of inciden- tal masses. However, in our study, such information is not available. Also, filling the questionnaires by the pa- tients and in case of patients’ tending to report lower body weighs in some studies and some methodological differences such as the use of waist circumference or hip circumference parameters instead of body mass in- dex in some other studies have resulted in different out- comes reporting different risk ratios and suggesting that obesity is only a risk factor for women and even that obesity is not a risk factor for kidney cancer. Howev- er, outcomes of the studies conducted by the European Prospective Investigation into Cancer and Nutrition Re- search Group (EPIC) on about 350.000 Europeans have shown that obesity is an important risk factor for RCC (6). In this study, it was reported that while all of the pa- rameters used for obesity evaluation in women (such as BMI, body weight, waist circumference, waist circum- ference) increased the risk of kidney cancer, only the hip circumference as a risk factor in men was reported to have a predictive value. Many hypotheses have been proposed to explain why obesity is a risk factor for RCC cases. Scacchi et al showed high serum concentrations of free insulin-like growth factor-I in obese patients(17). This factor affects cell cycle and is an important mutagenic factor associ- ated with many cancers, including breast, prostate, lung and colorectal. It is stated that obesity may increase Figure 2. Kaplan-Meier analysis of the cancer-specific survival of individuals in terms of body mass index. Figure 3. Kaplan-Meier analysis of the cancer-specific survival of individuals in terms of tumor stage. Figure 4. Kaplan-Meier analysis of the recurence-free survival of individuals in terms of body mass index. Prognostic factors in RCC-Ahmedov et al. Urological Oncology 100 Vol 15 No 03 May-June 2018 101 RCC risk by raising serum concentrations of free es- trogens in animal studies(18). Recently, it has been sug- gested that lipid peroxidation is a partially responsible mechanism for increased RCC risk in obese and hyper- tensive patients(19). These data suggest that increased BMI may also cause poor prognosis in RCC cases. But the results of the studies are far from supporting this assumption. Donat et al. retrospectively reviewed the data of 1137 RCC patients and reported that although an increased BMI was associated with a greater proportion of clear cell histology, comorbidity, and surgical morbidi- ty, BMI did not adversely impact overall or progres- sion-free survival(9). Reeves et al.(20) followed up 1.2 million women on avarage for 5.4 years for cancer incidence and 7.0 years for cancer mortality. They found that increasing body mass index was associated with an increased incidence of kidney cancer in addi- tion to many other cancers (trend in relative risk per 10 units=1.53, 95% confidence interval 1.27 to 1.84) and concluded that increasing body mass index is associat- ed with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Kamat et al.(10) reviewed the records of 400 patients who underwent ne- phrectomy for localized RCC. Their findings revealed that overweight and obese patients with renal cell car- cinoma have a more favorable prognosis than patients with a normal BMI and they concluded that if others confirm their finding that a high BMI confers a surviv- al advantage to patients undergoing nephrectomy, BMI may prove to be an important prognostic factor in renal cell carcinoma. We also found that a high BMI score leads to better prognosis in RCC patients in our study, similar to the results of Kamat et al. In a large cohort study conducted in Korea, the data of 1017 patients were retrospectively reviewed. After a mean follow-up of 76.9 months, the authors found that overweight and obese patients had less aggressive tumors, such as less lymph node and/or distant metastases, low pathological T stage and low Fuhrman grade vs normal weight pa- tients. In terms of cancer specific survival and overall survival multivariate analysis showed that overweight and obese patients had good survival rates compared to those with a body mass index in the normal range in the cohort (T1-4NallMall) groups. In addition, over- weight and obese status was significantly associated with cancer specific and overall survival in the T1- 4N0M0 groups. They concluded that overweight and obese Korean patients with RCC have more favorable pathological features and a better prognosis than those with a normal BMI(21). Similar results were obtained with the above studies in our study. We found that can- cer-specific survival and recurrence-free survival were better in the overweight and obese patient group than Prognostic factors in RCC-Ahmedov et al. Table 4. Univariate and multivariate analysis model for overall survival. Variables Univariate Multivariatec HRa 95% CIb P value HRa 95% CIb BMId Group 1 1.28 (0.88-1.32) 0.004 1.34 (1.02-1.42) Group 2 1.09 (0.92-1.22) 0.028 1.21 (0.96-1.39) Group 3 0.92 (0.82-1.14) 0.036 1.22 (1.06-1.38) Sex Male 1.06 (0.89-1.21) 0.584 - Female 1.02 (0.91-1.21) 0.480 - Smoking Yes 1.36 (1.21-1.58) 0.043 1.44 (1.22-1.56) Amount (cigarettes/day) 1-10 1.17 (0.88-1.21) 0.038 1.28 (1.19-1.32) 10-20 1.23 (1.15-1.32) 0.026 1.33 (1.26-1.42) > 20 1.38 (1.24-1.43) 0.018 1.45 (1.39-1.56) Duration (years) 1-10 1.19 (1.11-1.25) 0.021 1.24 (1.18-1.31) 11-20 1.24 (1.17-1.41) 0.017 1.35 (1.22-1.43) No 1.08 (1.03-1.22) 0.022 1.19 (1.09-1.24) Hypertension Yes 1.02 (0.89-1.14) 0.086 - No 1 - - Operation type Partial 1.68 (1.56-1.72) 0.004 1.72 (1.62-1.79) Radical 2.13 (1.99-2.24) 0.023 2.34 (2.18-2.44) Operation method Open 1.04 (0.96-1.12) 0.880 - Laparoscopic 1.08 (0.99-1.19) 0.420 - Histological subtypes Clear cell 1.14 (0.99-1.21) 0.560 - Chromophobe 1.09 (1.03-1.14) 0.226 - Stage T1a 1.17 (1.08-1.22) 0.004 1.22 (1.18-1.33) T1b 1.39 (1.15-1.48) 0.021 1.49 (1.36-1.55) T2a 1.69 (1.58-1.79) 0.019 1.75 (1.68-1.84) T2b 1.98 (1.84-2.21) 0.024 2.28 (2.12-2.88) T3a 2.23 (2.12-2.46) 0.038 2.49 (2.31-2.65) eGFR < 45 2.16 (1.89-2.32) 0.012 2.38 (2.21-2.49) 45-60 1.86 (1.74-1.99) 0.005 2.04 (1.92-2.32) > 60 1.62 (1.54-1.78) 0.049 1.92 (1.82-2.18) a Hazard ratio b Confidence interval c Multivariate analysis included variables that were significant (p < 0.05) in univariate analysis in the normal group, but we did not find any significant difference between the genders. However this study allows us to obtain important in- formation on the impact of BMI on the prognosis of RCC, it has several limitations. First of all, this study is a retrospective analysis of data collected from a sin- gle center; hence the number of cases is relatively small and limited to calculate the general population. In addi- tion, the loss of body weight and preoperative nutrition- al status are also reported to be significant prognostic factors for RCC(22), but our study did not include these. Smoking is also considered as an important risk factor for RCC. Several cancerous substances found in ciga- rettes cause cancers with different relative risk ratios in many other organs and increase the risk of developing RCC by 1.4-2.3 times(23). The risk of developing kid- ney cancer is directly related to the number of cigarettes consumed per day and the duration of use. Smoking cessation decreases the risk of developing cancer and then this reduction rate reaches 30% in 10 years. In our study, we also found that the survival of smokers was lower than non-smokers. The mean age of women in our study was significantly lower than that of men (38.3 vs 60.7). The birth rate in our country is quite high (2.3 - 4.2%)(24). Accordingly, women are frequently exposed to physician control at a young age and are consulted to urologists with renal masses that the obstetricians identify incidentally at the ultrasound. We consider that the age difference mainly depends on this. We stratified the patients according to ASA groups as it could affect survival rates. We con- sider that the ASA score did not affect the survival rates because the vast majority of the patients (80.5%) were in low-risk group (ASA I-II). Although preliminary reports of hypertension and diu- retic use indicate different risk factors for kidney can- cer, recent studies have shown that only hypertension is a risk factor and diuretics are not a risk factor(25). In our study, there was no statistically significant difference between the two groups, although hypertensive patients had less mean survival time than those without hyper- tension. As for surgical treatment, death and recurrence were observed in 5 patients after partial nephrectomy in our study. We found that survival rate was better in cases underwent partial nephrectomy than those underwent radical nephrectomy. We think that this is due to the larger tumor size of patients who underwent radical ne- phrectomy. For this reason, the number of deaths and recurrences was higher in radical nephrectomy group. Decreased renal function in RCC patients is a com- mon finding. It has been shown that low eGFR affects overall survival in patients undergoing surgery for RCC and nephron sparing surgery is recommended in these patients(26). Similarly, we found that the low eGFR level significantly reduced CSS and RFS in our study. Lymph node involvement may be predicted by preoperative radiologic imaging and some predictive models(27). In our clinic, we perform lymph node dis- section (LND) in RCC patients who have lymph node enlargement in preoperative imaging and peroperative suspicious lymph node involvement. However, we did not include the LND effect in this analysis because the data of these patients are incomplete and we do not have a standard protocol. Nowadays, in the treatment of renal tumors, laparo- Prognostic factors in RCC-Ahmedov et al. scopic radical nephrectomy and partial nephrectomy operations can be successfully performed with both transperitoneal and retroperitoneal approaches. When the EAU guidelines were analyzed, it has been stated that the laparoscopic approach resulted in lower mor- bidity, equivalent oncologic outcomes in T1-2 tumors in experienced hands, and possibly equivalent onco- logic outcomes in T3a tumors (Grade of evidence: 3). Laparoscopic radical nephrectomy is recommended as a treatment option in experienced centers (Recommen- dation level: B). There was no significant difference in survival rates after open and laparoscopic surgery in our study. Based on this result, we concluded that laparo- scopic method can be utilized as a standard approach in the treatment of kidney tumors. RCC is known as a heterogeneous malignancy with different clinical and pathological subgroups. Papillary and chromophobe RCCs constitute approximately 15- 25 % of total renal cancers and have a better progno- sis than the clear cell RCC group(28,29). In our study, no statistically significant difference was found between histologic subtypes in terms of survival. Tumor stage is the most important factor determining RCC prognosis(30). Tumor stage was also an important prognostic factor in our study. CSS and RFS decreased as tumor stage increased. CONCLUSIONS BMI was significantly associated with prognosis in pa- tients with RCC. Our findings indicate that overweight and obese RCC cases, which are determined by BMI, have a more favorable prognosis. However, our find- ings need to be supported by multicentre, prospective studies including more number of patient groups and longer oncologic follow-up period. ACKNOWLEDGEMENT This study was approved by Ege University local ethics committee. CONFLICT OF INTEREST The authors report no conflict of interest. REFERENCES 1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007; 18: 581-92. 2. Rodriguez-Covarrubias F, Gomez-Alvarado MO, Sotomayor M, et al. Time to Recurrence after Nephrectomy as a Predictor of Cancer- Specific Survival in Localized Clear-Cell Renal Cell Carcinoma. Urol Int. 2011; 86: 47- 52. 3. Parker WP, Cheville JC, Frank I, et al. Application of the Stage, Size, Grade, and Necrosis (SSIGN) Score for Clear Cell Renal Cell Carcinoma in Contemporary Patients. Eur Urol. 2017; 71: 665-73. 4. de Velasco G, Culhane AC, Fay AP, et al. Molecular Subtypes Improve Prognostic Value of International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Model. Oncologist. 2017; 22: 286-92. Urological Oncology 102 Prognostic factors in RCC-Ahmedov et al. 5. Karakiewicz PI, Suardi N, Capitanio U, et al. A preoperative prognostic model for patients treated with nephrectomy for renal cell carcinoma. Eur Urol. 2009; 55: 287-95. 6. Pischon T, Lahmann PH, Boeing H, et al. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer. 2006; 118: 728-38. 7. Weikert S, Boeing H, Pischon T, et al. Blood pressure and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition. Am J Epidemiol. 2007; 167: 438-46. 8. Patard JJ, Rodriguez A, Rioux‐Leclercq N, Guille F, Lobel B. Prognostic significance of the mode of detection in renal tumours. BJU Int. 2002; 90: 358-63. 9. Donat SM, Salzhauer EW, Mitra N, Yanke BV, Snyder ME, Russo P. Impact of body mass index on survival of patients with surgically treated renal cell carcinoma. J. urol. 2006; 175: 46-52. 10. Kamat AM, Shock RP, Naya Y, Rosser CJ, Slaton JW, Pisters LL. Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors. Urology. 2004; 63: 46-50. 11. Sobin L, Gospodarowicz M. Wittekind Ch. Eds. TNM Classification of Malignant Tumors: wiley-blackwell, Oxford; 2009. 12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999; 130: 461-70. 13. Ljungberg B, Bensalah K, Canfield S, et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015; 67: 913-24. 14. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014; 311: 806-14. 15. Bergström A, Hsieh C, Lindblad P, Lu C, Cook N, Wolk A. Obesity and renal cell cancer–a quantitative review. Br J Cancer. 2001; 85: 984. 16. Drabkin HA, Gemmill RM. Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC). Adv Cancer Res. 2010; 107: 39-56. 17. Scacchi M, Pincelli A, Cavagnini F. Growth hormone in obesity. Int J Obes. 1999; 23: 260- 71. 18. Hodgson AV, Ayala-Torres S, Thompson EB, Liehr JG. Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis. Carcinogenesis. 1998; 19: 2169-72. 19. Gago-Dominguez M, Castelao JE, Yuan J-M, Ross RK, Mimi CY. Lipid peroxidation: a novel and unifying concept of the etiology of Vol 15 No 03 May-June 2018 103 renal cell carcinoma (United States). Cancer Causes Control. 2002; 13: 287-93. 20. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 2007; 335: 1134. 21. Jeon HG, Jeong IG, Lee JH, et al. Prognostic value of body mass index in Korean patients with renal cell carcinoma. J. urol. 2010; 183: 448-54. 22. Morgan TM, Tang D, Stratton KL, et al. Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma. Eur Urol. 2011; 59: 923-8. 23. Nomiya T, Tsuji H. Renal Cell Carcinoma. Carbon-Ion Radiotherapy: Springer; 2014: 241-9. 24. Sahin H, Sahin H. Reasons for not using family planning methods in Eastern Turkey. The European Journal of Contraception & Reproductive Health Care. 2003; 8: 11-6. 25. Shapiro JA, Williams MA, Weiss NS, Stergachis A, LaCroix AZ, Barlow WE. Hypertension, antihypertensive medication use, and risk of renal cell carcinoma. Am J Epidemiol. 1999; 149: 521-30. 26. Pettus JA, Jang TL, Thompson RH, Yossepowitch O, Kagiwada M, Russo P. Effect of baseline glomerular filtration rate on survival in patients undergoing partial or radical nephrectomy for renal cortical tumors. Paper presented at: Mayo Clinic Proceedings, 2008. 27. Thompson RH, Raj GV, Leibovich BC, Russo P, Blute ML, Kattan MW. Preoperative nomogram to predict positive lymph nodes during nephrectomy for renal cell carcinoma. J. urol. 2008; 179:212. 28. Moch H, Gasser T, Amin MB, Torhorst J, Sauter G, Mihatsch MJ. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma. Cancer. 2000; 89: 604-14. 29. Beck SD, Patel MI, Snyder ME, et al. Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Ann Surg Oncol. 2004; 11: 71-7. 30. Brierley JD. TNM classification of malignant tumours: John Wiley & Sons; 2017.