Outcomes Following CT-Guided Percutaneous Radiofrequency Ablation of Primary Renal Tumors

Abstract: Purpose: The purpose of this study was to analyze outcomes in a single-center cohort of patients undergoing CT-guided percutaneous renal radiofrequency ablation (rRFA) to determine if lesion size was a differentiator of outcomes, and to describe the temporal changes in lesion size following rRFA. Materials and Methods: Forty lesions in 37 patients (27 males, 10 females; mean age 70±13 years) were treated with rRFA from 2006 to 2013. Patient, tumor, and treatment characteristics were analyzed. Statistical analysis included the entire treated cohort with particular attention paid to subgroupings based on (a) whether patients had a renal mass <3 cm or ≥3 cm, and (b) whether the lesion was biopsy-proven renal-cell carcinoma (RCC). To evaluate lesion changes after ablation, a mixed-effects ANOVA model was fit to lesion size values over time. Results: Kaplan-Meier survival curves showed trends toward worse primary recurrence and overall survival in lesions ≥3 cm, but these were not statistically significant (P=.13 and P=.27 respectively). Secondary recurrences were the same in both groups. The rate of change over time in lesion size following rRFA did not differ significantly either by initial lesion size (P=.65), or between biopsy-proven and non-biopsy-proven RCC (P=.46). Conclusion: rRFA is safe and effective in treating kidney tumors. Overall success of tumor ablation was unrelated to initial size. Serial changes in tumor size after ablation are similar regardless of original size and whether the lesion had been proven RCC by biopsy.

Key words: carcinoma, renal cell carcinoma, radiofrequency ablation.

______________________________________________

Renal cell carcinoma (RCC) constitutes the majority of kidney malignancies.¹ The number of RCC cases is increasing with approximately 65,000 new cases diagnosed each year in the United States.^1,2 Almost twice as many men as women are diagnosed with RCC, and the age at diagnosis peaks between ages 50 and 80 years.^2,3 Cigarette smoking and obesity have consistently been established as risk factors.¹

Guidelines indicate active surveillance, surgical intervention, and minimally invasive therapy as management methods for RCC.⁴ Renal radiofrequency ablation (rRFA) is a favorable alternative in patients who are poor surgical candidates because it spares kidney tissue and retains renal function. Renal radiofrequency ablation has no negative effects on glomerular filtration rate in the short or intermediate term,⁵ and it also poses less risk for developing chronic kidney disease (CKD) when compared to radical nephrectomy.^6,7

Many studies have shown high clinical success rates for rRFA, especially in cases where the lesions are exophytic and <3 cm^8-11 or <4 cm.^12-15 The purpose of this study was to analyze outcomes in a single-center cohort of patients undergoing CT-guided rRFA, to determine if lesion size was noted to be a differentiator of outcomes, and to describe temporal changes in lesion size following rRFA in patients with smaller vs larger tumors.

Materials and Methods

Patient and Tumor Characteristics

IRB approval was obtained for this study. A retrospective review was performed of our single institutional experience performing CT-guided percutaneous RFA. From June 2006 to June 2013, 40 renal masses in 37 patients (27 males, 10 females; mean age, 70±13 years; range, 40-89 years) were ablated. One patient had bilateral tumors; another patient had 3 tumors (1 on the right kidney, 2 on the left kidney). Four patients had previous partial nephrectomy. Patient characteristics are summarized in Table 1. 

Tumor size ranged from 1.2 cm to 6.3 cm (mean, 2.9±1.1 cm). Nineteen lesions (7 clear cell, 6 papillary, 2 chromophobe, 2 mixed, 3 unspecified) were confirmed to be RCC by image-guided biopsy. Similar to our experience, routine biopsy prior to rRFA is often not performed.^6,10,12-14 Two lesions were parapelvic (central), and 38 lesions extended to the renal cortex (exophytic). Additional tumor characteristics are listed in Table 2.

Percutaneous rRFA Procedure

Prior to the procedure, informed consent was obtained from all patients. With patients under general endotracheal or laryngeal mask anesthesia and lying prone on the CT table, scanning was performed to determine the exact location of the lesions. The method of anesthesia was at the discretion of the treating anesthesiologist. Appropriate skin sites for ablation were prepped and draped in standard sterile fashion and locally anesthetized with 1% lidocaine. Under direct CT guidance, electrodes (range, 2.5 cm to 5 cm active tip) were inserted into the lesions (Figure 1). The electrodes were multitined in 32 cases (LeVeen; Boston Scientific) and Cool-Tip in 8 cases (Covidien). Adjustments were made to confirm precise positioning of the needle within the mass. Aside from variations in technique of each performing radiologist, manufacturer instructions were followed for power and ablation time (mean, 21±10 minutes). 

With LeVeen probes, ablations were performed until roll-off was achieved using a 200-watt generator; a second ablation was performed starting at 70% of the initial maximal ablation energy according to treatment guidelines until roll-off occurred. Tumors ≥3 cm were treated with overlapping lesions, often deep and centrally within the mass. After retracting and removing the needles, CT scanning was performed to evaluate for any procedural complications. Streaking in the perirenal fat and the presence of gas bubbles in the ablated bed provided indication of ablation efficacy on noncontrast study. Patients were extubated prior to transfer to the recovery room. Treatment characters are listed in Table 3.

Patient Follow-Up

Patients were scheduled for a pre- and post-contrast CT scans at 1, 3, and 6 months after the procedure followed by planned annual imaging for 5 years. Variations existed depending upon patient availability, scheduling conflict, and patient’s ability to receive iodinated contrast. The mean duration of follow-up for all patients was 19.3±17.5 months (median, 14.1 months). Twenty patients were followed up with dual-phase CT,⁵ with noncontrast CT alone,⁸ with MRI, and 1 with PET CT. Two patients were lost to follow-up, while 1 patient had not yet reached the 1-month follow-up point.

Analysis & Statistics

The analysis included the entire treated cohort, with particular attention paid to subgroupings based on (a) whether patients had a renal mass <3 cm (Group 1) or ≥3 cm (Group 2) and (b) whether or not the lesion was biopsy-proven RCC. Student t test, Fisher exact test, and chi-square test were performed via MedCalc to compare patient, lesion, and treatment characteristics between Groups 1 and 2. Kaplan-Meier (KM) survival curves were also created via MedCalc to analyze primary recurrence and overall survival.

To evaluate lesion changes over time after rRFA, a mixed-effects ANOVA model was fit to lesion size values over time. Fixed effects included a separate intercept for each subgroup and a separate slope over time for each subgroup. Random effects included the random effect for patient nested within subgroup and a random slope over time for each patient nested within subgroup. An intercept for the overall population was estimated as the equally weighted average of the intercept over the subgroups, and similarly for slope over time. The test of equality of slopes between subgroups was conducted as a t test within this ANOVA model. 

The ANOVA model was fitted to lesion sizes as reported and also to log-transformed lesion sizes. As neither model provided a clearly superior fit to the data, results are reported from the model without log transformation.

Results

Only one patient had residual enhancing tumor after the initial rRFA at 1-month follow-up; all other lesions showed no enhancement on the first post-treatment scan. In this case, a repeat ablation was performed approximately 3 months after the initial procedure. Three lesions demonstrated recurrence (range, 9.7-28.6 months post-ablation), 2 were treated by repeat ablations, and 1 was treated by partial nephrectomy. The initial sizes of these lesions were 6.3 cm, 3.5 cm, and 3.3 cm (mean, 4.4 cm). As of last follow-up, there was no secondary recurrence after reintervention.

Patients who had lesions ≥3 cm were significantly older (mean age, 76±10 vs 65±13, P<.005). There were no significant differences in glomerular filtration rate (P=.74), serum creatinine (P=.44), number of prior interventions (P=.61), gender (P=.15), ethnicity (P=.49), or a history of diabetes, hypertension, and other diseases (P=.97) between the two groups. There was also no significant difference in lesion location (P=.49), kidney side affected (P=.34), and type of probe used during ablation (P=.58). Lesions ≥3 cm were treated with larger probes (chi-square test, P<.005) and ablated for longer periods of time (mean time, 25+10 vs 16+6 minutes, P<.005) than lesions <3 cm. Although KM survival curves (Figure 1) showed trends toward worse primary recurrence (P=.13, Figure 2A) and overall survival (P=.27, Figure 2B) in larger lesions, these trends were not statistically significant.

Serial changes in lesion size after ablation were modeled as a function of time. The rate of change over time in lesion size following rRFA did not differ significantly either by initial lesion size (<3 cm vs ≥3 cm, P=.65; Figure 3A), or between biopsy-proven and non-biopsy-proven RCC (P=0.46; Figure 3B). The regression line for the <3 cm group was lesion size (cm)=2.2139 cm–0.02208 cm×(number of months). For the ≥3 cm group, the regression line was lesion size (cm)=3.6034 cm–0.01683 cm×(number of months). These models thus estimate a reduction in treated lesion size (maximal diameter) over the course of 3 months by 0.066 cm in the <3 cm group, and by 0.050 cm in the ≥3 cm group. Over 12 months, estimated reductions in treated lesion size are 0.265 cm in the <3 cm group and 0.202 cm in the ≥3 cm group.

The pooled intercept and slope for the entire population based on equal weighting over the 2 groups yielded the following regression line: lesion size (cm)=2.9087 cm–0.01946 cm×(number of months). This model thus estimates a reduction of 0.058 cm in treated lesion size over the course of 3 months and 0.233 cm over 12 months.

The regression line for the lesions that were not biopsy-proven RCC was lesion size (cm)=3.236 cm–0.01547 cm×(number of months). For biopsy-proven RCC, the regression line was lesion size (cm)=2.6276 cm–0.02376 cm×(number of months). These models thus estimate a reduction in treated lesion size (maximal diameter) over the course of 3 months by 0.046 cm in the non-biopsy-proven group, and by 0.071 cm in the biopsy-proven group. Over 12 months, estimated reductions in treated lesion size are 0.186 cm in the non-biopsy-proven group and 0.285 cm in the biopsy-proven group.

Results for the pooled intercept and slope for the entire population based on equally weighting over these 2 groups were very similar to the intercept and slope pooled over the <3 cm group and the ≥3 cm group.

Two out of 3 recurrent lesions were biopsy-proven papillary RCC. Whether or not a lesion was biopsy-proven RCC was not a significant factor in determining primary recurrence (Fisher exact test, P=.33).

Complications

Eight out of 37 total patients experienced complications after rRFA. The severity of the complications was determined using the Society of Interventional Radiology (SIR) Clinical Practice Guidelines.¹⁶ In our study, minor complications included hemorrhage that did not require a blood transfusion (1), mild perinephric hematoma (2), flank pain (3), postprocedure urinary tract infection (1), hydronephrosis (2), gastroenteritis (1), and diarrhea (1). Major complications included thermal injury to an intercostal nerve (1), chronic hematuria (1), renal insufficiency (1), and colon injury (1). The patient with colon injury had a posteriorly positioned splenic flexure that sustained thermal injury during rRFA despite CT evidence of a sufficient fat plane between the RFA probes and the colon; this patient underwent colonic resection. There were no other major unplanned procedures following rRFA.

Discussion

Thermal ablation techniques including RFA and cryoablation (CA) have demonstrated efficacy in treating renal tumors. A recent review of published series studied 385 patients with 445 renal masses—all measuring ≤3.0 cm—treated by either RFA (n=256 tumors in 222 patients) or CA (n=189 tumors in 163 patients).¹⁷ At a mean follow-up of 2.8 years, 7 cases of recurrence and a 4.3% complication rate were found for RFA. Following cryoablation, 4 cases of recurrence (mean, 0.9 years after treatment) and 4.5% complication rate were observed. There were no significant differences between RFA and CA for technical success, complication rates, and recurrence rates. The authors, however, recommended cryoablation for large lesions due to the ability of cryophobes to create large ice balls of up to 8 cm. They noted that cryoablation may be preferential for centrally located lesions due to published results that described failures, limitations, and incomplete ablations associated with central lesions treated by RFA.^18-20 The size of cryoablated lesions may also decrease to a greater degree and at a faster rate than those treated by RFA.²¹ In another series comparing CA (n=600 cases) to RFA (n=775 cases), RFA-treated lesions had significantly higher rates of local tumor progression and a greater tendency toward metastatic progression.²² Nevertheless, most studies indicate similar clinical outcomes for RFA and CA (Table 4).^17,21,23-24

A comparison of RFA and partial nephrectomy has resulted in mixed findings (Table 5). In one study of renal tumors in solitary kidneys, RFA had lower morbidity and complication rates than laparoscopic partial nephrectomy.²⁵ Another study found no significant difference between the two methods for 5-year disease-free survival probability, local recurrence-free survival probability, and metastasis-free survival probability.²⁶ Although patients with independent risk factors
associated with increased recurrence were excluded in this study, others argue that the outcomes of RFA and partial nephrectomy cannot be directly compared because of selection bias.^6,27,28 For example, current partial nephrectomy patients tend to be younger with fewer comorbidities, contributing to increased overall survival rates.^6,28 

Our report compares favorably to prior studies that have demonstrated high technical success rates and low complication rates for rRFA (Table 6). Similar to prior results, we found a higher rate of primary recurrence for lesions ≥3 cm in maximal diameter. In fact, there was no recurrence for smaller tumors. However, the absolute rate of recurrence was still very low for tumors ≥3 cm (3 out of 19 treated lesions [16%]). After recurrent tumors were treated by repeat rRFA, there was no difference in secondary recurrence or need for additional therapy between the 2 groups. Notably, patients with larger lesions can still be successfully treated by RFA, although a second ablation may be necessary in some patients. Many studies similarly show high secondary success rates after repeat ablation.^6,12,29 Thus, tumor size alone should not be considered a contraindication to rRFA as long as close surveillance is performed to allow repeat ablation if needed. 

Overall complications were noted in 8 out of 37 patients (22%). Four patients (11%) experienced major complications requiring either an unplanned hospital admission or an unplanned increase in patient care. Four patients (11%) experienced minor complications that did not require extra patient care, hospital stay, or intervention. One patient with a pre-existing history of CKD started dialysis 39 months after treatment. No other patients started dialysis after rRFA treatment, confirming the safety of the procedure in preserving viable renal mass.

Gervais et al¹⁸ noted that 6 months after ablation, 20 out of 23 tumors decreased in size only slightly by 1 cm or less; the remaining 3 tumors decreased by more than 1 cm.³⁰ To our knowledge, no prior work has described serial changes to lesion size following RFA intervention in detail. Therefore, we tracked lesion size at each follow-up appointment after the initial procedure. A linear regression model illustrated that the decline in lesion size after rRFA was similar despite the baseline diameter of the treated lesion. Another linear regression analysis showed post-rRFA reduction in size was preserved regardless of whether or not the lesion was a biopsy-proven RCC. In our series, recurrent tumors increased in size with new contrast enhancement in follow-up images. Familiarity with the anticipated temporal course in lesion size may be important in early assessment of recurrence, particularly in patients unable to receive iodinated contrast for CT scans.

Conclusion

Renal radiofrequency ablation safely and effectively treats kidney tumors, including RCC. Complication and recurrence rates are more common in lesions ≥3 cm, but major complications remain low. A repeat ablation may be necessary in a small percentage of patients with larger lesions. In this group, a lack of subsequent recurrence suggests that size alone should not be considered a contraindication to rRFA treatment. After ablation, serial changes in lesion size are similar regardless of the original size and regardless of whether the lesion had been biopsy-proven RCC.

Acknowledgements

The authors would like to thank Yitzchak David, MPH, for providing the statistical analysis of the data, and David Daniel for his assistance in researching reference materials.

References

1. Lipworth L, Tarone RE, and McLaughlin JK: The epidemiology of renal cell carcinoma. J Urol. 2006;176(6 Pt 1):2353-2358.
2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
3. Tareen B, Harper W, Garg S, et al. FirstConsult: Renal cell carcinoma. 2010. https://www.mdconsult.com.
4. Alberta Provincial Genitourinary Tumour Team. Renal Cell Carcinoma. Edmonton, Alberta, Canada: Alberta Health Services, Cancer Care; 2012.
5. Pettus JA, Werle DM, Saunders W, et al. Percutaneous radiofrequency ablation does not affect glomerular filtration rate. J Endourol. 2010;24(10):1687-1691.
6. Takaki H, Yamakado K, Soga N, et al. Midterm results of radiofrequency ablation versus nephrectomy for T1a renal cell carcinoma. Jpn J Radiol. 2010;28(6):460-468.
7. Lucas SM, Stern JM, Adibi M, Zeltser IS, Cadeddu JA, Raj GV. Renal function outcomes in patients treated for renal masses smaller than 4 cm by ablative and extirpative techniques. J Urol. 2008;179(1):75-79.
8. Watanabe F, Kawasaki T, Hotaka Y, et al. Radiofrequency ablation for the treatment of renal cell carcinoma: initial experience. Radiat Med. 2008;26(1):1-5.
9. Hiraoka K, Kawauchi A, Nakamura T, Soh J, Mikami K, Miki T. Radiofrequency ablation for renal tumors: Our experience. Int J Urol. 2009;16(11):869-873.
10. Nitta Y, Tanaka T, Morimoto K, et al. Intermediate oncological outcomes of percutaneous radiofrequency ablation for small renal tumors: initial experience. Anticancer Res. 2012;32(2):615-618.
11. Varkarakis IM, Allaf ME, Inagaki T, et al. Percutaneous radio frequency ablation of renal masses: results at a 2-year mean followup. J Urol. 2005;174(2):456-460.
12. Ferakis N, Bouropoulos C, Granitsas T, Mylona S, Poulias I. Long-term results after computed-tomography-guided percutaneous radiofrequency ablation for small renal tumors. J Endourol. 2010;24(12):1909-1913.
13. Tracy CR, Raman JD, Donnally C, Trimmer CK, Cadeddu JA. Durable oncologic outcomes after radiofrequency ablation: experience from treating 243 small renal masses over 7.5 years. Cancer. 2010;116(13):3135-3142.
14. Levinson AW, Su LM, Agarwal D, et al. Long-term oncological and overall outcomes of percutaneous radio frequency ablation in high risk surgical patients with a solitary small renal mass. J Urol. 2008;180(2):499-504.
15. Zagoria RJ, Traver MA, Werle DM, Perini M, Hayasaka S, Clark PE. Oncologic efficacy of CT-guided percutaneous radiofrequency ablation of renal cell carcinomas. AJR Am J Roentgenol. 2007;189(2):429-436.
16. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol. 2003;14(9 Pt 2):S199-S202.
17. Atwell TD, Schmit GD, Boorjian SA, et al. Percutaneous ablation of renal masses measuring 3.0 cm and smaller: comparative local control and complications after radiofrequency ablation and cryoablation. AJR Am J Roentgenol. 2013;200(2):461-466.
18. Gervais DA, McGovern FJ, Arellano RS, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma: Part I. Indications, results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol. 2005;185(1):64-71.
19. Gupta A, Raman JD, Leveillee RJ, et al. General anesthesia and contrast-enhanced computed tomography to optimize renal percutaneous radiofrequency ablation: multi-institutional intermediate-term results. J Endourol. 2009;23(7):1099-1105.
20. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Solid renal tumors: an analysis of pathological features related to tumor size. J Urol. 2003;170(6 Pt 1):2217-2220.
21. Raman JD, Hall DW, Cadeddu JA. Renal ablative therapy: radiofrequency ablation and cryoablation. J Surg Oncol. 2009;100(8):639-644.
22. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer. 2008;113(10):2671-2680.
23. Pirasteh A, Snyder L, Boncher N, Passalacqua M, Rosenblum D, Prologo JD. Cryoablation vs. Radiofrequency Ablation for Small Renal Masses. Acad Radiol. 2011;18(1):97-100.
24. El Dib R, Touma NJ, Kapoor A. Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies. BJU Int. 2012;110(4):510-516.
25. Turna B, Kaouk JH, Frota R, et al. minimally invasive nephron sparing management for renal tumors in solitary kidneys. J Urol. 2009;185(2):2150-2157.
26. Olweny EO, Park SK, Tan YK, Best SL, Trimmer C, Cadeddu JA. Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical t1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up. Eur Urol. 2012;61(6):1156-1161.
27. Zagoria RJ, Pettus JA, Rogers M, Werle DM, Childs D, Leyendecker JR. Long-term outcomes after percutaneous radiofrequency ablation for renal cell carcinoma. Urology. 2011;77(6):1393-1397.
28. Faddegon S, Cadeddu JA. Does renal mass ablation provide adequate long-term oncologic control? Urol Clin North Am. 2012;39(2):181-190.
29. Balageas P, Cornelis F, Le Bras Y, et al. Ten-year experience of percutaneous image-guided radiofrequency ablation of malignant renal tumors in high-risk patients. Eur Radiol. 2013;23(7):1925-1932.
30. Gervais DA, McGovern FJ, Arellano RS, McDougal WS, Mueller PR. Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiol. 2003;226(2):417-424.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no disclosures related to the content of this manuscript.

Manuscript received February 16, 2014; provisional acceptance given March 18, 2014; final version accepted March 25, 2014. 

Address for correspondence: John H. Rundback, MD, 718 Teaneck Road, Teaneck, New Jersey 07666, United States. Email: rundback@mail.holyname.org

Suggested citation: Lee N, Rundback JH, Herman KC, Kerns J, Barkama R. Outcomes following CT-guided percutaneous radiofrequency ablation of primary renal tumors. Intervent Oncol 360. 2014;2(4):E18-E31.