renal cell carcinoma ( rcc ) is among the most frequent malignant tumors with significant morbidity and mortality . more than 58,000 estimated new cases and more than 13,000 deaths occurred in the united states in 2010 . during the last decades , an increase in the incidence of all clinical stages of renal tumors was observed , with the greatest increase for localized tumors . owing to the wide use of cross - sectional abdominal studies such as ultrasound , computed tomography ( ct ) , and magnetic resonance imaging ( mri ) , the detection rate of small solid lesions has increased , with up to 66% of tumors found incidentally . the majority of incidentally diagnosed rcc tends to be of smaller size and thus is more likely to be asymptomatic , show a lower histological grade , and have a decreased incidence of metastasis . radiofrequency ablation ( rfa ) is a novel minimally invasive therapeutic approach that should be offered to patients with small renal tumors with a size less than 4 cm in diameter or significant comorbidities precluding surgical resection . in the need for a therapeutic approach for such selected cases , rfa was established at our institution in 2006 . in the present study we sought to assess the efficacy , complications , and changes in renal function in our initial cases after an intermediate follow - up period . percutaneous rfa was offered to highly selected patients whose renal tumors did not exceed 40 mm in diameter . patient selection was limited to subjects with advanced age and severe comorbidities that would cause a high surgical risk , impaired renal function prior to treatment , a functional or anatomical solitary kidney , or bilateral renal tumors or patients who refused tumor resection . after an initial implementation and learning process during which no renal biopsies were done , biopsies were routinely performed a few days before rfa under ct guidance . all rfas were performed under general anesthesia with a rita device ( model 1500 rf generator , 25 cm starburst xl semi - flex rfa device , angiodynamics , queensbury , ny , usa ) by an interventional radiologist . according to the kidney protocol of the rita device , the maximum power to achieve a target temperature of 105 was 150 w. depending on the target size , the time of each cycle varied . for a desired ablation defect of 20 mm , we used 5 minutes at the target temperature with a reset time of 5 minutes with a second identical cycle . for a 30-mm defect , we analogously used 7 minutes , and for a 40-mm defect , 8 minutes . if necessary , overlapping ablations were performed by repositioning the probe and restarting the procedure . at the end of the ablation , after the probe had been removed , a control ct scan verified the ablation and excluded complications . patients were examined the day after the procedure through physical examination , ultrasound , and blood samples . the patients ' renal function was assessed immediately before rfa , the day after rfa , and at follow - up by estimating the glomerular filtration rate ( egfr ) with the mdrd equation , as modified in 2005 : egfr=175(creatinine ) (age)(0.742 if female ) . four definitions of treatment outcomes were used : complete and incomplete treatment and suspected and verified recurrence . complete treatment was defined as a lack of contrast enhancement in combination with shrinkage or a stable size of the ablated tumor at the first follow - up mri / ct . conversely , incomplete treatment was defined as contrast enhancement or progression in tumor size at the first follow - up imaging study after treatment . suspected tumor recurrence was defined as contrast enhancement or extension in size in any subsequent imaging in initially completely treated patients . suspected tumor recurrence turned into a verified recurrence either when a renal biopsy of the lesion was positive for vital tumor tissue or when the site of the formerly ablated lesion further increased . patients with rcc or an unknown histology were followed with contrast mri or ct every 3 months after treatment in the first year and then every 6 months , whereas oncocytoma patients were followed every 6 months . statistical analyses , including the related - samples wilcoxon signed - rank tests and the chi - square test , were performed with ibm spss ver . after an initial implementation and learning process during which no renal biopsies were done , biopsies were routinely performed a few days before rfa under ct guidance . all rfas were performed under general anesthesia with a rita device ( model 1500 rf generator , 25 cm starburst xl semi - flex rfa device , angiodynamics , queensbury , ny , usa ) by an interventional radiologist . according to the kidney protocol of the rita device , the maximum power to achieve a target temperature of 105 was 150 w. depending on the target size , the time of each cycle varied . for a desired ablation defect of 20 mm , we used 5 minutes at the target temperature with a reset time of 5 minutes with a second identical cycle . for a 30-mm defect , we analogously used 7 minutes , and for a 40-mm defect , 8 minutes . if necessary , overlapping ablations were performed by repositioning the probe and restarting the procedure . at the end of the ablation , after the probe had been removed , a control ct scan verified the ablation and excluded complications . patients were examined the day after the procedure through physical examination , ultrasound , and blood samples . the patients ' renal function was assessed immediately before rfa , the day after rfa , and at follow - up by estimating the glomerular filtration rate ( egfr ) with the mdrd equation , as modified in 2005 : egfr=175(creatinine ) (age)(0.742 if female ) . four definitions of treatment outcomes were used : complete and incomplete treatment and suspected and verified recurrence . complete treatment was defined as a lack of contrast enhancement in combination with shrinkage or a stable size of the ablated tumor at the first follow - up mri / ct . conversely , incomplete treatment was defined as contrast enhancement or progression in tumor size at the first follow - up imaging study after treatment . suspected tumor recurrence was defined as contrast enhancement or extension in size in any subsequent imaging in initially completely treated patients . suspected tumor recurrence turned into a verified recurrence either when a renal biopsy of the lesion was positive for vital tumor tissue or when the site of the formerly ablated lesion further increased . patients with rcc or an unknown histology were followed with contrast mri or ct every 3 months after treatment in the first year and then every 6 months , whereas oncocytoma patients were followed every 6 months . statistical analyses , including the related - samples wilcoxon signed - rank tests and the chi - square test , were performed with ibm spss ver . 18.0 ( ibm co. , armonk , ny , usa ) . mean tumor size was 26.2 mm ( range , 15 to 42 mm ) , mean length of hospital stay was 1.4 days ( range , 1 to 4 days ) , and mean follow - up was 23.8 months ( range , 3 to 59 months ) . thirty - five of the 44 tumors were biopsied before rfa ( 79.6% ) . in biopsied patients , rcc was the prevalent histology in 68.6% and oncocytoma was the prevalent histology in 14.3% ; 17.1% of cases were benign or inconclusive . grade i complications occurred in 11 patients ( 25% ) and grade ii complications in 1 case ( 2.3% ) . all grade i complications ( pain or elevated temperature ) were treated conservatively with anti - inflammatory drugs , whereas the one patient with the grade ii complication ( perirenal bleeding ) received two units of blood without the need for any further surgical interventions ( table 2 ) . overall changes in renal function and a precise breakdown of every patient are shown in table 3 . at more than 2 years after the treatment , the mean serum creatinine increased by 0.14 mg / dl on average ( p<0.004 ) . stratified by length of follow - up , the increase was not significant in the first 24 months but was after 24 months ( difference , 0.24 mg / dl ; p<0.001 ) . mean egfr decreased significantly by 7.5 ml / min from 65.9 ml / min before treatment to 58.4 ml / min at maximum follow - up ( range , -55.2 to 17.3 ml / min ; standard deviation [ sd ] , 13.04 ; p=0.004 ) . the distribution of patients in the corresponding egfr subgroups ( 60 , 59 - 30 , 29 - 15 , and 15 ml / min ) did not change significantly from before therapy to maximal follow - up ( p=0.08 ) . forty - three of 44 ablated tumors ( 97.5% ) were classified as completely treated on the first imaging study at follow - up , which normally took place 1 to 3 months after rfa ( table 4 ) . this patient is currently under active surveillance with no sign of tumor progression or recurrence .   in 8 of 43 cases ( 18.6% ) the suspected recurrences were observed after an average of 23.9 months ( range , 11 to 43 months ) and had an average size of 22.6 mm ( range , 15 to 30 mm ; sd , 7.0 ) . of those eight suspected recurrences , five ( 62.5% ) turned out to be false - positives whereas three ( 37.5% ) were confirmed ( table 5 ) . the false - positive recurrences showed a negative ( repeat ) biopsy or , if the patient refused biopsy , showed no further contrast enhancement on subsequent imaging ( 10 or 12 months after suspected recurrence ) . average follow - up until occurrence of the false - positive recurrences was 25.2 months ( range , 11 to 43 months ) . the three proven recurrences ( 7.7% ) were noted at 12 , 23 , and 30 months after rfa . one patient developed metastatic disease and is currently being treated with tyrosine kinase inhibitors . in our cohort , the overall survival was 87.5% ; five patients died from comorbidities , and renal tumors were not responsible for their deaths . in patients with verified rcc , the tumor - free survival rate was 90% and the metastasis - free survival rate was 95.8% at a mean follow - up of 23.3 months . grade i complications occurred in 11 patients ( 25% ) and grade ii complications in 1 case ( 2.3% ) . all grade i complications ( pain or elevated temperature ) were treated conservatively with anti - inflammatory drugs , whereas the one patient with the grade ii complication ( perirenal bleeding ) received two units of blood without the need for any further surgical interventions ( table 2 ) . overall changes in renal function and a precise breakdown of every patient are shown in table 3 . at more than 2 years after the treatment , the mean serum creatinine increased by 0.14 mg / dl on average ( p<0.004 ) . stratified by length of follow - up , the increase was not significant in the first 24 months but was after 24 months ( difference , 0.24 mg / dl ; p<0.001 ) . mean egfr decreased significantly by 7.5 ml / min from 65.9 ml / min before treatment to 58.4 ml / min at maximum follow - up ( range , -55.2 to 17.3 ml / min ; standard deviation [ sd ] , 13.04 ; p=0.004 ) . the distribution of patients in the corresponding egfr subgroups ( 60 , 59 - 30 , 29 - 15 , and 15 ml / min ) did not change significantly from before therapy to maximal follow - up ( p=0.08 ) . forty - three of 44 ablated tumors ( 97.5% ) were classified as completely treated on the first imaging study at follow - up , which normally took place 1 to 3 months after rfa ( table 4 ) . this patient is currently under active surveillance with no sign of tumor progression or recurrence . in 8 of 43 cases ( 18.6% ) initially classified as complete ablations , radiologists suspected tumor recurrences during follow - up . the suspected recurrences were observed after an average of 23.9 months ( range , 11 to 43 months ) and had an average size of 22.6 mm ( range , 15 to 30 mm ; sd , 7.0 ) . of those eight suspected recurrences , five ( 62.5% ) turned out to be false - positives whereas three ( 37.5% ) were confirmed ( table 5 ) . the false - positive recurrences showed a negative ( repeat ) biopsy or , if the patient refused biopsy , showed no further contrast enhancement on subsequent imaging ( 10 or 12 months after suspected recurrence ) . average follow - up until occurrence of the false - positive recurrences was 25.2 months ( range , 11 to 43 months ) . the three proven recurrences ( 7.7% ) were noted at 12 , 23 , and 30 months after rfa . one patient developed metastatic disease and is currently being treated with tyrosine kinase inhibitors . in our cohort , the overall survival was 87.5% ; five patients died from comorbidities , and renal tumors were not responsible for their deaths . in patients with verified rcc , the tumor - free survival rate was 90% and the metastasis - free survival rate was 95.8% at a mean follow - up of 23.3 months . ablative techniques like percutaneous rfa are emerging because they offer an alternative to surgical excision , especially for elderly patients with impaired health . with the better understanding of the growth kinetics and behavior of small renal tumors [ 7 - 9 ] tumor size seems to be a predictor of the tumor growth rate , whereas size alone is an insufficient parameter to distinguish between rcc with a so - called benign biological behavior from one with an aggressive behavior . others have reported that the aggressive potential of rcc increases beyond a diameter of 30 mm . imaging is not presently able to assess the malignancy of renal tumors : only angiomyolipoma can be diagnosed with sufficient accuracy . renal biopsy is a safe procedure with an incidence of grade i complications of about 10% . biopsy success depends on tumor size and is diagnostic in 81% in tumors with an average size of 25 mm ( showing rcc in about 75% and benign histology in about 20% ) . a repeat biopsy , after an initial nondiagnostic one , provides similar diagnostic rates so that diagnosis for most patients can be achieved . in terms of avoiding unnecessary and unjustified procedures owing to benign , unknown , or inconclusive histology , we recommend our strategy of taking a renal biopsy under local anesthesia a few days before rfa . with a biopsy rate of nearly 80% , our study differs from most of the previously published studies [ 12 - 19 ] . unlike most previously published series [ 12 - 22 ] ( table 6 ) , we used a generally accepted grading system of complications , thus guaranteeing transparency and comparability . the minimally invasive nature of this procedure was confirmed by the low rate of complications in our setting : only minor complications occurred in 27% ( grade i , 25% ; grade ii , 2.3% ) . rfa is associated with a significantly lower incidence of complications , morbidity , and mortality compared with tumor resection , especially laparoscopic nephron - sparing surgery . complications after partial or radical nephrectomy are more likely to occur in older patients with preexisting comorbidities , and postoperative complications after nephrectomy are associated with a significantly higher risk of death . this should be taken into consideration when patients with comorbidities present with small asymptomatic renal tumors . the increase of serum - creatinine by 0.14 mg / dl at a 2-year follow - up and a slight decrease in egfr conforms to the literature . ablative techniques have little impact on renal function in subjects with regular renal function as well as in those with a solitary kidney or renal insufficiency . this is of particular interest because the association between impaired renal function and cardiovascular morbidity and mortality is well established . of note , we experienced a considerable discrepancy in suspected and proven recurrences during follow - up . interestingly , 62.5% of all suspected recurrences ( mean follow - up , 25.2 months ) showed no evidence of malignancy in the ( repeat ) biopsy or no further contrast enhancement in subsequent imaging under active surveillance . in one case , renal biopsy identified a focal inflammation that caused the contrast enhancement . the considerable number of false - positive suspected recurrences must be emphasized , because immediate retreatment , either with a second ablation or even with tumor resection , might be an unnecessary overtreatment . in cases of suspected recurrences , a repeat biopsy or even temporarily active surveillance in selected patients might be justified , especially in small , asymptomatic tumors . .   stated that active surveillance up to 1 year after post - therapeutic enhancement could be justified , because most of these enhancements are not a sign of recurrence but a result of postoperative inflammation immediately after rfa . however , their results relate to enhancements immediately after rfa and not to events occurring 11 to 43 months after rfa . second , not every patient underwent renal biopsy before rfa or if a recurrence was suspected . this was related to multiple factors such as the learning curve , the implementation process of rfa in our department , and patient 's choice . however , this was mitigated because we separately analyzed patients undergoing rfa with biopsy - proven rcc . third , renal function was assessed with serum creatinine and egfr and not with more accurate measures such as diethylene triamine pentaacetic acid - scans , thus diminishing the validity of our results in this field . the primary intention of the study was to report the efficacy of rfa in highly selected patients who were offered a treatment option and not to assess the influence of rfa on renal function . finally , follow - up was limited to a mean of 2 years ; changes in tumor - free survival or renal function might occur later on . owing to demographic changes , the increased incidence of renal tumors in the elderly , a better understanding of the growth kinetics and behavior of small renal tumors [ 7 - 9 ] , the low rate of complications [ 14,16 - 18,20 - 22 ] , and the only slight impairment of renal function , the role and importance of rfa might further increase in the future .