A total of 133 patients diagnosed with renal clear cell carcinoma at the Zhumadian Central Hospital from June, 2013 to June, 2015 were selected consecutively. The inclusion criteria for the present study were: T1-2N0M0 period in American Joint Committee on Cancer staging of RCCs, no secondary tumor in kidney or kidney stones, patients having completed surgical removal of the tumor and cytokines or sorafenib therapies, no participation in other clinical trials, good compliance and complete clinical data. The exclusion criteria for the study were: impaired kidney function, high level (doubled more than normal) of serum creatinine and urea nitrogen, hemoglobin <100 g/l; history of renal trauma, isolated kidney, solitary kidney, renal tuberculosis; serious hypertension and poor diabetes control, and disease of cardiovascular combined with cerebrovascular, liver function damage, and other underlying diseases intolerable of surgery.

Informed consent was obtained from patients and their families. The ethics committee at the Zhumadian Central Hospital approved the study protocol. The patients were divided into the surgery alone group (40 cases), surgery combined with cytokine group (45 cases) and surgery combined with sorafenib group (48 cases) according to the different treatments. The surgery alone group included 25 men and 15 women, aged 46–68 years with an average age of 57.5±10.3 years; tumor numbers were 1–3 with 1.6±0.5 on average; 32 cases of unilateral and 8 of bilateral; and maximum tumor diameters were 2–7.5 cm with 4.8±1.9 cm on average. The surgery combined with cytokines group included 28 men and 17 women, aged 43–69 years with an average age of 56.2±11.4 years; tumor numbers were 1–3 with 1.4±0.6 on average; 36 cases of unilateral and 9 of bilateral; and maximum tumor diameters were 2.5–8.0 cm with 4.9±1.6 cm on average. The surgery combined with sorafenib group included 29 men and 19 women, aged 44–72 years with an average age of 59.3±14.2 years; tumor numbers were 1–3 with 1.7±0.8 on average; 39 cases of unilateral and 9 of bilateral; and maximum diameters of the tumor were 2.5–8.5 cm with 5±1.7 cm on average. Differences of gender, age, tumor number, location and diameter in the 3 groups had no statistical significance (P>0.05).

The operative methods included radical resection and nephron sparing surgery, and open and laparoscopic surgery, which were carried out according to the standard of medical procedures performed by one surgical and nursing team. There was no statistically significance in the different surgeries of the 3 groups (P>0.05). In the cytokine group, interleukin (IL)-2 was selected for an intravenous injection of 72,000 IU/kg·8 h, used for 5 days followed with 2 days of break, for a total of ≤4-12 weeks. In the sorafenib group, sorafenib was injected at 400 mg each time, twice a day, for a total of 4–12 weeks. Any adverse reactions led to drugs being withdrawn.

The follow-up was continued to January, 2016 and the 2 groups were followed-up 6–30 months; average of 20 months. Recurrence rates, survival rates, serum creatinine, hemoglobin levels, the levels of serum vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, and drug adverse reaction rates of the 2 groups were compared as per the commonly used chemotherapy drug toxicity standard CTC 3.0 version. Serum creatinine and hemoglobin levels were detected using conventional biochemical assay, and VEGF and TNF-α were detected using ELISA. Kits were purchased from R&D Systems, Inc. (Minneapolis, MN, USA) and used as per the manufacturer's instructions.

SPSS 20.0 (IBM SPSS, Armonk, NY, USA) was used for data analysis and processing. Quantitative data were presented as mean ± standard deviation and groups were compared with single factor analysis of ANOVA. Qualitative data were expressed as cases number or percentage, and groups were compared using the χ² test. Survival time was compared using the Kaplan-Meier method (log-rank test). P<0.05 was considered to indicate a statistically significant difference.

The Kaplan-Meier method was used to determine the recurrence and survival rates of different treatments. The results revealed that the surgery combined with sorafenib group had a significantly lower recurrence and higher survival rates (Fig. 1) (P<0.05). The median survival period in the sorafenib group was >30 months while that in the other 2 groups was 27 months, with a significant statistical difference (χ²=6.214, P=0.045) (Table I).

Differences of preoperative serum creatinine and hemoglobin levels were not statistically significant (P>0.05). In 3 months of follow-up, creatinine levels were significantly elevated while hemoglobin levels were significantly decreased. The sorafenib group had decreased creatinine and higher hemoglobin levels than those in the other 2 groups (P<0.05) (Table II).

Differences of preoperative VEGF and TNF-α levels were not statistically significant (P>0.05). In the 3 months of follow-up, VEGF levels were reduced but TNF-α levels were increased. The sorafenib group had significantly lower VEGF and higher TNF-α levels than those in other 2 groups (P<0.05) (Table III).

The surgery combined with cytokine group had 6 cases of severe abdominal pain and diarrhea, 4 cases of headache, 5 cases of multiple organ dysfunction (such as myocardial ischemia, hypotension, respiratory difficulties, liver and kidney dysfunction, thrombocytopenia, anemia and mental disorders), with a total incidence of 33.3%. The surgery combined with sorafenib group had 3 cases of severe hand or foot skin reaction, 2 cases of hypertension, 1 case of diarrhea, 1 case of fatigue and loss of appetite, with a total incidence of 33.3%, which was significantly lower than those in the cytokine group (χ²=4.521, P=0.033).