Percutaneous Single-Probe Cryoablation vs Single-Electrode Radiofrequency Ablation for Treatment of Renal Tumors Less Than 2.5 cm
Abstract: Background: Current manufacturer guidelines for cryoablation of renal tumors measuring more than 1 cm include the use of multiple probes to achieve an adequate ablation margin. No prior studies have compared the use of single-probe cryoablation or single-electrode radiofrequency ablation (RFA) in the treatment of lesions greater than 1 cm. Objective: The aim of this study was to compare the clinical outcomes of lesions suspicious for renal cell carcinoma measuring 2.5 cm or less treated with percutaneous single-electrode RFA or single-cryoprobe technique. Methods: This retrospective review compared single-probe cryoablation to single-electrode RFA performed on 116 suspicious lesions in 107 patients over a 10-year period. The percutaneous intervention included a combination of CT and ultrasound-guidance utilizing a single 17-gauge cryoprobe or single multitine electrode. The primary outcome was defined as nonenhancement and either reduction in size or stability of the target lesion on follow-up contrast-enhanced CT or MRI performed at a minimum of 6 months (clinical success). Secondary outcomes included technical success (defined as nonenhancement on contrast-enhanced CT performed immediately following the ablation) as well as complications. Logistic regression analysis was performed to assess for predictors in outcome. Statistically significant differences between the two treatment modalities regarding patient demographics and lesion characteristics were assessed. A P value of <.05 was considered statistically significant. Results and limitations: Ninety-four percent of all RFA treatments (n=87) and 91% of all cryoablation treatments (n=29) were considered technically successful. Initial technical success was achieved in 93% of all RFA lesions (n=82) and 89% of all cryoablation lesions (n=25). On intent-to-treat basis, clinical success was achieved in 97% of RFA lesions (n=73) and 91% of cryoablation lesions (n=21, P=.21). If a lesion was initially treated successfully, 97% of those treated with RFA (n=70) and 95% of those treated with cryoablation (n=18) were ultimately clinically successful. The overall recorded complication rate was 6% (n=7), all occurring with RFA. Conclusion: Single-probe percutaneous cryoablation of renal masses measuring <2.5 cm is safe and comparable to percutaneous RFA.
Key words: radiofrequency ablation, cryoablation, renal cell carcinoma
Renal cell carcinoma (RCC) comprises up to 4% of all malignancies, with more than 64,000 cases and 13,000 deaths estimated to have occurred in 2012.1,2 The incidence of RCC has increased considerably in the past 3 decades, mainly due to the early detection of incidental small lesions on cross-sectional abdominal imaging such as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI) for unrelated conditions.3-6
Surgical resection of RCC remains the gold standard of treatment; however, percutaneous and laparoscopic ablation of RCC is a well established and widely accepted alternative in appropriately selected patients.3-10 Cryotherapy in particular has been studied since 1981 and is now accepted with radiofrequency ablation (RFA) as a potential treatment option for renal cell carcinoma.6-8
In laboratory porcine and phantom models analyzing different combinations of size and quantity of cryoprobe, single probes compared with multiple probes created low percentages of lethal ice (colder than -30°C).12,13 Littrup et al assessed the effects on the proportions of lethal ice in phantoms in one to four cryoprobes.12 The single cryoprobe resulted in an average lethal ice diameter of 1.2 cm. As a result, for renal tumors measuring more than 1 cm, current manufacturer recommendations are to use more than one cryoprobe to achieve an adequate ablation margin.13
The purpose of this retrospective study was to compare the efficacy in the treatment of lesions measuring 2.5 cm or less utilizing contemporary commercially available single-electrode RFA or single-cryoprobe technique.
Materials and Methods
After approval from the Vancouver General Hospital Ethics Review Board, a retrospective review was conducted of all patients referred between November 2001 and March 2012 for percutaneous thermal ablation of renal tumors with imaging characteristics suspicious for RCC. Multidisciplinary renal tumor board consensus was required to proceed with ablation. Ablation was indicated if patients were not surgical candidates due to comorbid condition, had predisposition to recurrent RCC (warranting maximum renal function preservation, such as Von Hippel-Lindau Syndrome), had easily accessible lesions from a percutaneous approach, and had lesions not adjacent to or abutting central structures (such as the vein, calyx, or ureter). A single percutaneous ablation procedure on a single lesion was performed by 1 of 3 experienced interventional radiologists.
The procedure was performed within the CT suite using a combination of CT and ultrasound guidance. A single multitine electrode (3.0 cm or 3.5 cm LeVeen needle; Boston Scientific) or 17 ga cryoprobe (IceSphere or IceRod; Galil Medical) was inserted. For RFA, at the operator’s discretion, 1 or 2 stacked ablations were performed. For cryoablation, a single cycle including a freeze of 8-10 minutes, passive thaw of 5-8 minutes, and freeze of 8-10 minutes was performed. Additional cycles were performed at the discretion of the operator.
The aim of the procedure was to achieve an ablation margin of at least 1 cm with both RFA and cryoablation, as documented on intraprocedural noncontrast CT scanning.13 The noncontrast CT was utilized in addition to assess for intraprocedural complications. Immediately following ablation, the needles were removed, and a postcontrast CT scan was performed in those with sufficient renal function (GFR of 60 or more), and a noncontrast CT scan was performed in those with significant renal impairment (GFR less than 30). For those patients with a GFR between 30 and 60, appropriate premedication and hydration were administered (oral N-acetylcysteine, intravenous sodium bicarbonate, or 0.9% saline) prior to the procedure, in accordance with local departmental guidelines.
The patient was observed for at least 4 hours post procedure and discharged home on the same day if clinically well. Patients who failed to meet discharge criteria were admitted for observation along with further analgesic control if deemed necessary by the admitting urologist.
Follow-up of the treated lesions consisted of a contrast-enhanced CT or MRI at 3, 6, and 12 months post treatment. If the patient had significant renal impairment, the nephrology department was consulted to determine the most appropriate investigation and premedication, as contrast enhancement was deemed necessary for follow-up. The ablation zone was assessed to ensure interval stability or reduction in size.
The primary outcome measure was clinical success, defined as nonenhancement and either reduction in size or stability of the target lesion on follow-up contrast-enhanced CT or MRI performed at a minimum of 6 months. If enhancement was noted on a follow-up scan performed before 6 months, this was included as a clinical failure if there was a renal tumor board consensus to repeat the treatment with an alternative ablative technique. If enhancement was noted before 6 months, and a 6-month scan was yet to be performed, the lesion was excluded from analysis for clinical success, due to the possibility of spontaneous involution, which has been described in the literature.15,16 If the lesion demonstrated residual enhancement at 6 or more months, but was then successfully treated by the same repeat ablative technique, this was considered clinically successful.
The major secondary outcome was technical success, defined as nonenhancement on contrast-enhanced CT performed immediately following the ablation or demonstration of an ice ball that encompassed the lesion on noncontrast CT for those with renal insufficiency. Both technical success per individual treatment and initial technical success for each individual lesion were analyzed.
Patient demographics were recorded. In addition, lesion depth and level was recorded, as described by Gervais et al and Schmit et al and classified as exophytic, parenchymal, or central, and upper, middle, or lower pole (Table 1).17,18 Lesion location was assessed by review of preprocedural or intraprocedural images on the hospital picture archiving and communication system (PACS), if available. For those lesions where the images were no longer available, the official radiology report for the preprocedural or intraprocedural imaging was accessed from the hospital radiology information system (RIS). Complication rates were also recorded, and classified according to the Society for Interventional Radiology (SIR) clinical practice guidelines.19
Logistic regression analysis was performed using the SAS software package (version 9; SAS Institute Inc.) to assess for predictors in outcome. Statistically significant differences between the two treatment modalities regarding patient demographics (age and sex) and lesion characteristics (size and location) were assessed. A P value of <.05 was considered statistically significant.
Over the 10-year period, 191 treatment sessions were performed on 164 patients with 178 lesions (mean diameter 2.5 cm, range 0.8 cm – 4.8 cm). One hundred and sixteen lesions (mean diameter 1.9 cm, range 0.8 cm – 2.5 cm) in 107 patients (63 males, 44 females) met the radiologic criteria for enrollment in the study, with a total of 126 treatment sessions. There were 2 patients with 2 lesions, 1 patient with 4 lesions, and 1 patient with 5 lesions. Mean patient age was 65 years, and median age 67 years (range 36 years – 87 years).
Of the 116 lesions, 75% (n=87) were treated with RFA only, 23% (n=27) were treated with cryoablation only, and 2% (n=2) were treated with both (Figure 1, Table 2). One of the 2 lesions treated with both RFA and cryoablation was treated with RFA initially but had recurrence at 6 months and was eventually successfully treated with cryoablation. The second lesion was treated initially with cryoablation, with recurrence at 3 months, was then treated with RFA, but also demonstrated recurrence 3 months following the second treatment. It was treated a third time with RFA, achieving technical success, but has yet to undergo further follow-up. Ninety-four percent of all RFA treatments (n=88) and 91% of all cryoablation treatments (n=29) were considered technically successful (Table 2).
Initial technical success was achieved in 93% of all RFA lesions (n=82) and 89% of all cryoablation lesions (n=25) (Table 2). Of the 6 RFA lesions that met the criteria for technical failure (Table 3), 3 were treated with repeat RFA; 2 of these were eligible for follow-up and were clinically successful. The third lesion achieved technical success but was lost to follow-up and clinical success could not be assessed. Of the 3 cryoablation lesions that met the criteria for technical failure, two were retreated with cryoablation, both of which were technically and clinically successfully treated; the third lesion continued to be monitored out to 12 months with surveillance imaging due to concerns regarding cardiac comorbidities, and the possibility that the residual enhancement may spontaneously involute. At 12 months, it continued to demonstrate residual enhancement, but remained stable in size, thus still meeting the criteria for clinical failure.
Eighty-four percent of lesions treated with RFA (n=75) and 79% of cryoablation lesions (n=23) had 6 or more months of follow-up. On an intent-to-treat basis (including all patients allocated to a particular treatment, regardless of whether technical success was initially achieved), clinical success was achieved in 97% of RFA lesions (n=73) and 91% of cryoablation lesions (n=21; P=.21) (Table 4). Of those lesions that demonstrated initial technical success, 88% (n=72) of RFA lesions and 76% (n=19) of cryoablation lesions were eligible for follow-up (Table 2). If a lesion was initially treated successfully, 97% of those treated with RFA (n=70) and 95% of those treated with cryoablation (n=18) lesions were ultimately clinically successful (Table 4).
No statistically significant differences in outcome between the 2 treatment groups were noted regarding patient age or sex, or lesion level or size. There were, however, statistically significant negative outcomes in rates of clinical success of deeper lesions treated with RFA compared with more superficial lesions treated with RFA (P=.02).
The overall recorded complication rate was 6% (n=7) (Table 5, Figure 2). One patient experienced hematuria, which resulted in an overnight hospital admission (SIR category B), and the remainder did not warrant further treatment (SIR category A).19 The most common complication was retroperitoneal hematoma, comprising 29% of complications (n=2). All recorded complications occurred with RFA.
Cryoablation presents potential advantages compared with RFA including better patient comfort and tolerance often resulting in lower doses of conscious sedation.20 This technology also offers the benefit of increased intraprocedural visualization, so that active monitoring with ultrasound, CT, or MRI can be undertaken.6 Cryoablation has also been proven in porcine models and humans to be safer than RFA when lesions are located adjacent to critical structures of the renal hilum, such as the collecting system or renal vessels.21,22
Kunkle and Uzzo undertook a meta-analysis comparing outcomes of clinically localized small renal masses treated by cryoablation or RFA.23 Forty-seven studies representing 1,375 renal lesions were analyzed, treated by open, laparoscopic, or percutaneous techniques. The conclusion was that cryoablation results in fewer retreatments and improved local tumor control, as well as the potential for lower risk of metastatic progression compared with RFA.
All of the literature describing cryoablation, and comparing cryoablation with RFA, to our knowledge, describes the multiple-probe technique. There are several limitations with multiple probe cryoablation including increased procedure time and potential increased patient morbidity due to the need to insert multiple cryoprobes percutaneously. The increased cost and technical challenges associated with multiple probe insertion is also problematic.
In addition to the limitations associated with the multiple-probe technique, cryoablation poses additional infrastructure problems, mainly regarding the utilization and storage of large gas tanks, whereas RFA or microwave ablation can be utilized on demand, without any additional infrastructure required.
Both percutaneous RFA and cryoablation of renal tumors have been described in the literature, and both are well accepted treatment options in appropriately selected patients. In review articles and retrospective studies that specifically address cryoablation, multiple probes have always been utilized for renal tumors measuring more than 1 cm.3,5,24 In fact, multiple-probe cryoablation has been described as the treatment of choice for large renal masses, which measure 3 cm or larger, due to the large ice ball than can be achieved by placing each probe 1-2 cm apart from each other, to achieve an ice ball margin of at least 5 mm to avoid residual tumor.17,24-26
In lesions treated initially with RFA, regardless of subsequent repeat treatments with either RFA or cryoablation, the technical success rate was 93% (Table 2). Technical success rates for every RFA treatment undertaken (including repeat treatments) was 94% (Table 2). This is comparable to numerous studies assessing technical success of RFA, which report rates between 79% and 100%.6
In lesions treated initially with cryoablation, again regardless of subsequent repeat treatments, the observed technical success rate was 89% (Table 2). A technical success rate for cryoablation treatments undertaken, including repeat treatments, was 91% (Table 2). When compared with the RFA technical success rates, this difference was not statistically significant.
For lesions treated with RFA, the most common technical failure was inaccurate needle positioning, resulting in an ablation defect away from the target lesion. This occurred in 50% of technical failures (n=3). This is possibly due to difficulties in monitoring of the ablation margin once RFA has commenced, especially with ultrasound, which is the real-time modality of choice in our institution. In comparison, only a single technical failure (33%) occurred with cryoablation, due to inaccurate needle placement. This suggests a possible benefit of real-time monitoring of the ice ball. The most common technical failure in lesions treated with cryoablation was residual tumor on the periphery (66%, n=2), similar to the 33% of lesions treated with RFA (n=2) presenting with residual tumor on the periphery.
There was no statistically significant difference in outcomes with lesions treated with cryoablation when compared with RFA, with clinical success of 91% vs 97% (P=.21). If a treated lesion achieved initial technical success, the clinical success rates for lesions treated with cryoablation and RFA were again statistically insignificant (P=.62) at 95% and 97% respectively. These results suggest that comparable outcomes between the 2 treatment types are attainable.
The 6% complication rate compares favorably with other studies, which report an overall complication rate of 1% to 18%.4,27,28 All complications were reported to have occurred with RFA. Of the 7 complications, 2 were intraprocedural imaging-confirmed retroperitoneal hematomas. This is an unusual finding, as a lower rate of bleeding is often reported in RFA procedures as opposed to cryoablation, due to the active coagulation associated with heat and documented compromised platelet function at low temperatures resulting in a transient localized coagulopathy.27,29 A possible reason for the absence of significant cryoablation complications may be due to the single-probe technique, as all studies that have reported increased cryoablation-related bleeding rates utilized a multiple-probe technique.
The rationale for the utilization of a single cryoprobe for renal masses measuring 2.5 cm or less is to increase patient safety and comfort by reducing procedure time and to limit the number of needle insertions and significantly reduce the procedure cost, all while utilizing the previously described advantages of cryoablation. The presented study represents, to the authors’ knowledge, the first analysis of the use of percutaneous single-probe cryoablation in the setting of small renal masses for single-session curative intent. The high number of lesions treated in this study (n=116) ensures statistical integrity in spite of the disproportionate number of lesions treated with RFA (n=88) as compared to cryoablation (n=28).
The limitations of the study include its retrospective nature, and relatively short minimum follow-up period of 6 months. The 6-month time frame was however deemed to be the most appropriate minimal follow-up period to judge clinical success as this interval has been extensively validated as an appropriate surrogate for clinical success in numerous other studies.30,31 The small number of lesions treated in the cryoablation group (n=28 vs n=88 for the RFA group) is an additional limitation.
Furthermore, each lesion was treated based on imaging characteristics and some without biopsy, resulting in the possible treatment of non-malignant tumors such as oncocytomas that could translate into a confounding variable, however the random nature of these events would have resulted in equal representation in both cohorts.
Finally, the retrospective nature of this study also highlights the possibility of under- or over-reporting of complications associated with the procedure. We did not include postprocedure non-clinically significant small perinephric hematomas as a relevant complication, as this is often observed due to the inherent hypervascular nature of renal tumors and renal parenchyma.
The presented retrospective analysis of 116 lesions suggests that single-probe percutaneous cryoablation of small renal masses <2.5 cm is safe and comparable to percutaneous RFA.
Editor’s note: Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest related to the content herein.
Manuscript received December 17, 2014; provisional acceptance given February 20, 2015; manuscript accepted June 3, 2015.
Address for correspondence: Mark Power, MBBS, Department of Radiology, St. George Hospital, Gray St., Kogarah, NSW, Australia 2217. Email: firstname.lastname@example.org.
Acknowledgement: The authors acknowledge Michael Schulzer, MD, PhD, for his contributions to this manuscript.
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