The influence of body mass index on the long-term survival of patients with renal cell carcinoma after tumour nephrectomy


Axel Haferkamp, Department of Urology, University of Heidelberg, INF 110, 69120 Heidelberg, Germany.



To assess whether under- or overweight at the time of surgery has any effect on the survival of the patients with renal cell carcinoma (RCC), as obesity increases the risk of developing RCC.


We prospectively evaluated 780 patients who had nephrectomy for RCC between 1990 and 2005. We used uni- and multivariate Cox proportional hazards models to assess the effect of body mass index (BMI), tumour stage, Fuhrman grade, age, sex, histological type and performance status on cancer-specific survival (CSS). Patients were grouped according to BMI (in kg/m2), as underweight (<18.5), normal (18.5–<25), overweight (25–<30) and obese (≥30).


The median (range) follow-up was 5.3 (0.5–15.4) years, the patients being followed until June 2006; 254 patients died during the follow-up. Multivariate analyses of all patients showed that tumour stage, Fuhrman grade, Karnofsky performance status, age, sex and BMI were independent prognostic factors for CSS. While underweight patients had a significantly worse prognosis than those of normal weight, overweight or obese patients had a similar outcome to that of patients of normal weight. In a subgroup analyses including patients with localized RCC only, there was a strong tendency to less aggressive disease in the overweight group (P = 0.081).


Being underweight is an unfavourable and new risk factor for CSS in patients with RCC treated by nephrectomy. Although not significant, there seems to be a limited favourable prognostic effect of overweight on CSS in patients with localized RCC.


body mass index


cancer-specific survival


hazard ratio


performance status


National Institutes of Health.


Several epidemiological studies have consistently suggested that obesity is related to an increased risk of developing RCC in women and men [1–5]. The hypothetical reasons for this increased risk include higher levels of oestrogen, insulin and growth factors in adipose tissue, and hypertension and immune malfunction [6].

Although obesity appears to double the risk of developing RCC, some evidence showed that patients with RCC and a higher body mass index (BMI) at diagnosis have better survival than those with a lower BMI [7–11]. To date, the data supporting this inverse association remain somewhat questionable because of specific limitations in the existing studies. These include the retrospective design of the studies, the absence of data of important covariates, and the evaluation of subgroups only. In addition, all authors have focused on overweight and obese patients only, and compared them with a group of combined normal and underweight patients (BMI < 25 kg/m2). No study of RCC has described the prognostic influence of underweight. This is surprising, as Flegal et al.[12] showed that being underweight was associated with greater mortality than in those of normal weight in the National Health and Nutrition Examination Survey.

Therefore the aim of the present study was to evaluate the prognostic influence of BMI (in kg/m2), grouped as underweight (<18.5) , normal (18.5–<25), overweight (25–<30) and obese (≥30) on cancer-specific survival (CSS) of prospectively assessed patients with RCC.


In all, 780 patients with RCC who had no previous malignant tumour and who had a radical nephrectomy at the authors’ institution between 1990 and 2005 were entered into a prospective database. The median (range) age of the patients was 61.6 (14.6–89.0) years; 319 were aged <60 years and 461 were ≥60 years, and 494 were male and 286 were female.

According to the 1997 American Joint Committee on Cancer TNM staging system, the tumour stage was I in 412 patients (52.8%), II in 77 (9.9%), III in 141 (18.1%) and IV in 150 (19.2%). The tumour histological type and grade were determined according to the 1997 WHO classification and Fuhrman’s criteria. The carcinomas were clear-cell in 646 specimens (86.1%), chromophilic in 70 (9.3%), chromophobic in 30 (4.0%) and collecting duct in four (0.5%), with 30 not classified by the pathologist. The Fuhrman grade was 1 in 186 specimens (24.0%), 2 in 431 (55.7%), 3 in 156 (20.3%) and 4 in one (0.1%), with six not classified by the pathologist. At the time of surgery 714 patients (91.5%) had a Karnofsky performance status (PS) of ≥80% and 66 of <80%.

The BMI was classified as a four-level categorical variable according to the USA National Institutes of Health (NIH); 10 patients were underweight at the time of surgery, 245 were normal, 361 were overweight and 141 were obese, with 23 not evaluated. The median (range) BMI was 26.6 (15.7–46.3) kg/m2.

Of the 10 underweight patients, eight had stage I tumours, one stage II and one stage III. According to Kim et al.[13,14], five of these patients had signs of cachexia, including weight loss (one), hypoalbuminaemia (three), anorexia (one) or malaise (one).

Patients were prospectively evaluated every 3 months for the first 2 years after treatment, every 6 months for the next 3 years, and yearly thereafter, with a chest X-ray or thoracic CT, abdominal ultrasonography or CT or MRI and serum chemistry. Patients were followed until June 2006. Survival was calculated from the date of nephrectomy. The survival endpoint was the date of the last follow-up or death. Kaplan-Meier estimates were used to describe survival rates, including point-wise asymptotic 95% CI. Patients who were confirmed to have died from other tumour were censored. Furthermore, assuming independence of the occurrence of RCC and other tumours in the same patient, patient survival was censored at the time of occurrence of a second malignancy. The study was approved by the institutional review boards.

The following clinical and pathological features were assessed for their prognostic relevance to the long-term survival the patients with RCC: age (≥60 vs <60 years), gender, Karnofsky PS (<80% vs ≥80%), tumour stage (II–IV vs I), Fuhrman grade (2 or 3 vs 1), histological type (clear cell vs other) and BMI (underweight, overweight or obesity vs normal). Univariate and multivariate analyses of prognostic factors were used within the Cox proportional hazards model. For each prognostic factor the hazard ratio (HR) in the univariate analysis and the adjusted HR in the multivariate analysis are given, including the 95% CI. In all tests, P < 0.05 was considered to indicate significance.


The median (range) follow-up was 5.3 (0.5–15.4) years; to June 2006, 254 patients (32%) had died from their disease. The CSS rate (95% CI) at 5 years after surgery for all patients was 67.3 (63.7–71)%; it was 47.6 (11.0–84.3)% in underweight patients, 62.1 (55.3–68.7)% in those of normal weight, 69.8 (64.4–75.0)% in overweight and 70.5 (62.2–78.7)% in obese patients. On univariate analyses, the risk of dying from RCC for overweight patients was reduced to ≈75% of that in those of normal weight (HR 0.77, 0.59–1.02, P = 0.067), and to about two-thirds for obese patients (HR 0.70, 0.48–1.01, P = 0.057). Being underweight had no significant influence on CSS in the univariate analysis (HR 1.48, 0.54–4.03, P = 0.443). Age, gender, Karnofsky PS, tumour stage, Fuhrman grade and clear cell subtype were significant univariate prognostic factors of CSS in these patients.

In the multivariate model of all patients, which included the univariate prognostic factors noted above and the four-level categorical variable BMI, the association between overweight or obesity and death from RCC was no longer evident. By contrast, being underweight at the time of surgery significantly increased the HR by more than four times that of patients of normal weight. Age >60 years, male sex, Karnofsky PS of <80%, tumour stage and Fuhrman grade 3 remained significant prognostic factors for dying from RCC in the multivariate model. The HRs, 95% CI and P values of the univariate and multivariate analyses for all patients are shown in Table 1.

Table 1.  Univariate and multivariate analysis of prognostic risk factors for long-term CSS of all patients with RCC, and of those with localized RCC (stage I and II)
VariableHR (95% CI), P
UnivariateMultivariate (721)Multivariate, localized RCC (456)
Age (≥60 vs <60 years)1.42 (1.09–1.83), 0.0081.43 (1.08–1.89), 0.0132.50 (1.42–4.39), 0.002
Gender (male vs female)1.68 (1.28–2.20), <0.0011.53 (1.14–2.05), 0.0042.06 (1.18–3.60), 0.011
Karnofsky PS (≥80% vs <80%)2.63 (1.83–3.77), <0.0011.73 (1.16–2.56), 0.0071.09 (0.37–3.22), 0.872
Tumour stage
 II vs I3.82 (2.33–6.26), <0.0013.25 (1.94–5.46), <0.0013.26 (1.87–5.67), <0.001
 III vs I6.39 (4.27–9.55), <0.0014.58 (2.94–7.13), <0.001 
 IV vs I25.5 (17.5–37.2), <0.00119.05 (12.5–28.9), <0.001 
Fuhrman grade
 2 vs 11.90 (1.29–2.80), 0.0011.16 (0.77–1.75), 0.4731.33 (0.73–2.43), 0.352
 3 vs 17.46 (5.02–11.1), <0.0012.20 (1.43–3.40), <0.0012.34 (1.02–5.38), 0.046
Histological type (clear cell vs other)1.69 (1.09–2.62), 0.0190.93 (0.59–1.48), 0.7652.42 (0.95–6.12), 0.063
 Underweight vs normal1.48 (0.54–4.03), 0.4434.27 (1.47–12.4), 0.0083.15 (0.77–12.8), 0.110
 Overweight vs normal0.77 (0.59–1.02), 0.0671.00 (0.75–1.34), 0.9890.60 (0.34–1.07), 0.081
 Obese vs normal0.70 (0.48–1.01), 0.0571.11 (0.74–1.65), 0.6130.68 (0.32–1.43), 0.306

In a multivariate subgroup analysis of 456 patients with localized RCC, including tumour stage I and II, there was a strong tendency (P = 0.081) for being overweight to reduce the risk of death from RCC to 60% of that in patients of normal weight. In obese patients the risk reduction was similar, at 68%, but this was not significant (P = 0.306). There was also a strong tendency for being underweight at surgery to worsen the patients’ prognosis 3.1 times. Age, gender, tumour stage, and Fuhrman grade remained significant prognostic factors for dying from RCC in this multivariate subgroup model. Table 1 also shows the HRs, 95% CIs and P values for the multivariate analyses of patients with localized RCC.


Based on the findings of several large epidemiological studies, obesity is considered a risk factor for developing RCC in adults [1–5]; in the present study we evaluated the prognostic influence of BMI on the CSS of patients with RCC treated with nephrectomy. The results indicate that, despite a strong trend for a better prognosis (as long-term CSS) for overweight or obese patients in the univariate analyses, this effect was no longer present in the multivariate model, where other known prognostic factors, i.e. gender, age, Karnofsky PS, tumour stage, histological subtype and Fuhrman grade, were included.

This result is in accordance with the retrospective studies [10,11]; Parker et al.[11] evaluated 970 patients with RCC and were unable to identify obesity (BMI ≥30 kg/m2) as a prognostic factor (HR 0.90, 0.65–1.23, P = 0.488) for CSS in their multivariate analysis, which also included the prognostic factors Mayo Clinic Stage, Size, Grade and Necrosis score, TNM stage groups, nuclear grade and tumour necrosis. They concluded that BMI offers little additional prognostic information beyond the accepted prognostic features. Donat et al.[10] evaluated 1137 patients with RCC who had had a radical or partial nephrectomy. In their multivariate analysis, only age >65 years, systemic symptoms, surgery type and pathological stage affected overall survival. While obesity (BMI ≥30 kg/m2) did not affect overall survival (HR 0.90, 0.62–1.30, P = 0.58), overweight (BMI 25–<30) was almost significant (HR 0.69, 0.48–1.00, P = 0.05).

Although we were unable to confirm these results in the multivariate analysis of all the present patients, the findings were similar, with a strong tendency to less aggressive disease in the overweight group, in the multivariate subgroup analysis including patients with localized RCC. Perhaps a BMI of 25–<30 kg/m2 has a limited positive prognostic effect in this group of patients. As the long-term survival rate of patients with localized RCC is so high, more patients than included in the present study (456) need to be evaluated to clearly identify being overweight as a positive prognostic factor in patients with localized RCC.

Two studies [7,8] reported findings indicating that overweight and/or obese patients had a more favourable prognosis than patients with a normal BMI. Yu et al.[7] evaluated 349 patients with RCC and available BMI data, and a median follow-up of 4.4 years. They reported a favourable prognosis in obese patients for disease-free survival (HR 0.43, 0.19–0.98) and overall survival (0.68, 0.38–1.22), but the study findings were limited by the retrospective design of the study.

A more contemporary review by Kamat et al.[8] of 400 patients with non-metastatic, node-negative RCC also showed a more favourable prognosis in overweight and obese patients than in those with a normal BMI for disease-free, overall and CSS. Unfortunately, that study also had some important limitations; it was retrospective, the median follow-up was relatively short (32 months) and the study did not control for other known prognostic factors, e.g. PS or histological subtype. Despite these limitations the results in that study underline our impression that being overweight at the time of surgery might have a limited positive prognostic effect in patients with localized disease.

To our knowledge no other study has focused on the effect of being underweight (<18.5 kg/m2) in the prognosis of patients with RCC. Most studies evaluating BMI in these patients defined ‘normal’ differently from the NIH definition of as a BMI of <25 kg/m2, therefore including patients who were underweight [8,10,11]. In the present study we used the NIH definition and identified 10 patients with a BMI of <18.5 kg/m2 as an additional subgroup. Our results indicate that being underweight at the time of surgery worsened the prognosis of patients by more than four times.

One reason for underweight can be cachexia, which is characterized by a complex, multilevel pathogenesis. It involves up-regulated tissue catabolism and impaired anabolism, release of tumour-derived catabolic factors and inflammatory cytokines, and neuroendocrine dysfunction. These culminate to create an energy-inefficient state characterized by wasting, chronic inflammation, neuroendocrine dysfunction and anorexia [15–17].

Cachexia-related findings, including weight loss of ≥2.5 kg within 3 months, hypoalbuminaemia, malaise or anorexia, were previously identified as an independent predictor of survival in patients with RCC [13,14]. Kim et al.[13] reported a prognosis of disease-free survival of three times worse, and 4.4 times worse for CSS, in cachectic than in non-cachectic patients when evaluating 250 with T1N0M0 RCC.

In the present group of 10 underweight patients, five presented with cachexia-like symptoms, as described above; in these patients cachexia was most likely the reason for the low BMI, but cachexia-like symptoms did not account for the low BMI in the other five patients. Several reasons for underweight other than tumour cachexia, including lifestyle and malnutrition, have been reported [18,19] and are probably the reason for being underweight in these five asymptomatic patients. These patients can only be identified as being at greater risk of dying from RCC when their BMI is calculated. This indicates that the groups of underweight and tumour cachexia partly overlap, with some patients in both groups and others in just one group.

Comparing the present study with published reports, there are advantages and limitations. As opposed to all other published reports, the present study was prospective, with a standardized follow-up after surgery for all patients. The present results also enhanced previous work in this area by evaluating a previously unstudied subgroup of BMI. Potential weaknesses include a possible selection bias associated with the referral pattern to a tertiary-care centre, and the relatively few patients compared to previous epidemiological studies.

In conclusion, the present results indicate that BMI offers additional prognostic information beyond the accepted prognostic features. Being underweight (BMI < 18.5 kg/m2) represents a new and unfavourable risk factor for CSS in patients with RCC treated by nephrectomy. Although not statistically significant, there was a limited but favourable prognostic effect of overweight (BMI 25–<30 kg/m2) on CSS in patients with localized RCC. The importance and prognostic implications of this finding need to be addressed in a large multi-institutional pooled analysis.


None declared.