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Cryoablation versus Radiofrequency Ablation for Renal Tumor Ablation: Time to Reassess?
COMMENTARY
Cryoablation versus Radiofrequency Ablation for Renal Tumor Ablation: Time to Reassess? Debra A. Gervais, MD ABBREVIATIONS IRE = irreversible electroporation, MW = microwave, RCC = renal cell carcinoma, RF = radiofrequency
Of the widely available methods for renal tumor ablation, cryoablation was the first to be assessed in the treatment of renal cell carcinoma (RCC) by using open surgical approaches. Open surgical access was necessary because early cryoprobes were too large for percutaneous application. Initial evaluation of percutaneous approaches to renal tumor ablation in humans included a “treat-and-resect” case reported by Zlotta et al (1) in 1997 and the first case with ablation as the sole planned treatment reported by McGovern et al (2) in 1999. With the advent of percutaneous needle applicators, renal tumor ablation moved to interventional radiology suites with ultrasound (US), computed tomography, and, in some cases, magnetic resonance imaging guidance. With percutaneous cryoprobes available shortly thereafter, the next several years saw expansion of the use of percutaneous image-guided radiofrequency (RF) ablation and cryoablation of renal tumors. Most recently, newer modalities such as microwave (MW) ablation and irreversible electroporation (IRE) have been assessed, and even promoted by some, to treat small tumors. The appeal of percutaneous needle applicators for tumor ablation was the avoidance of surgery in selected patients. Indications for renal tumor ablation include advanced age, multiple comorbid conditions, solitary kidneys, familial syndromes, or multiple sporadic RCC. Early experience with small tumors showed a high technical effectiveness rate with a low recurrence rate over short follow-up intervals (3–5). These early successes led to growing enthusiasm for its use in growing numbers of patients, as documented by a Surveillance, Epidemiology, and End Results database trend evaluation comparing the From the Department of Radiology, Abdominal Imaging and Intervention, Massachusetts General Hospital, White 270, 55 Fruit St., Boston, MA 02114. Received May 6, 2013; final revision received and accepted May 11, 2013. Address correspondence to D.A.G.; E-mail: [email protected] D.A.G. has received Massachusetts).
a
research
grant
& SIR, 2013 J Vasc Interv Radiol 2013; 24:1135–1138 http://dx.doi.org/10.1016/j.jvir.2013.05.030
from
Covidien
(Mansfield,
use of radical nephrectomy, partial nephrectomy, and tumor ablation between 2004 and 2007 (6). What was also clear from early experience is that tumor size matters for almost any measure of therapy effectiveness. For small tumors measuring 4 cm or less (ie, T1a), cryoablation and RF ablation showed technical effectiveness rates in the range of 87% to 97% in cohorts with short follow-up periods (7–10). What has not been assessed in randomized trials is comparative effectiveness of RF ablation and cryoablation. With the advent of new devices on the market such as those used to perform MW ablation and IRE, the question of which ablation method is optimal for RCC not only persists but garners new attention. The peerreviewed literature consists of an ever-increasing number of cohort studies with varying protocols for tissue diagnosis, follow-up, and method of ablation.
WHICH IS BETTER FOR SMALL RENAL MASSES: RF ABLATION OR CRYOABLATION? For practices with cryoablation and RF ablation systems or for practices seeking to purchase a first ablation system, the question is often phrased as, “Which is better for small renal masses: RF ablation or cryoablation?” A number of factors contribute to the difficulty in developing randomized trials to answer this question. Among the major drivers are the following challenges: (i) existing extirpative therapies for T1a renal tumors such as complete nephrectomy or partial nephrectomy are associated with high local recurrence-free survival (RFS) and disease-free survival rates (11); (ii) accumulated evidence suggests that any difference in RFS between RF ablation and cryoablation, if any such difference exists, is likely to be very small (7–10); and (iii) given the success of extirpative therapies, existing guidelines recommend tumor resection as a standard therapy with ablation as an option for a smaller number of selected patients (12).
1136
’
Commentary: Cryoablation vs RF Ablation for Renal Tumors
To seek an answer comparing RF ablation and cryoablation performance in the treatment of RCC requires the question to be defined with a more measurable parameter. For partial nephrectomy, 5-year RFS rates are higher than 97% (11). Newer percutaneous modalities are therefore held to a very high standard. Any meaningful survival data must include 5-year RFS. For new procedures, 5-year survival means, at a minimum, that studies must accrue and follow up patients for 5 years and sometimes more, even though Kaplan–Meier log-rank tests adjust for some patients to enter into the study for shorter periods of time than the interval studied. Published reports with 5-year RFS have appeared for RF ablation and cryoablation in recent years (10,13–16). For cryoablation, reports include laparoscopic and percutaneous cryoablation as a result of the earlier adoption of cryoablation via surgical approaches. That now leaves in a current state with a tumor that has an excellent prognosis of 97% 5-year disease free survival after extirpative therapy and growing data on two ablation modalities with 5-year disease-free survival rates in the range of 87%–97%. Although RFS after partial nephrectomy is better than after tumor ablation, the gap in the 5-year RFS rates between surgery and best reported ablation results is small. In addition, the 5-year RFS ranges for cryoablation and RF ablation overlap substantially. Proponents of each side debate the relative merits of each ablation modality in panels with no clear data-driven consensus, but with proponents arguing for a small incremental gain in their preferred method of treatment by selecting reports that favor their favored modality. Neither side has sufficient data to provide a definitive and final answer. What do existing reports tell us about RFS after cryoablation and RF ablation of small renal masses? Any difference in RFS between cryoablation and RF ablation for the treatment of T1a RCC is nonexistent or very small. Two metaanalyses reached different conclusions (8,9) regarding effectiveness but did not specifically compare 5-year RFS. Kunkle and Uzzo (8) reported local progression rates of 12.9% versus 5.2% for RF ablation and cryoablation, respectively. In contrast, El Dib et al (9) reported 90% and 89% effectiveness for RF ablation and cryoablation, respectively, with no statistically significant difference, and concluded that it is urgent to perform trials with long-term data to determine whether RF ablation or cryoablation is better. How to go about assessing such a difference for those who believe it exists will be illustrated next. Any real difference in RFS is likely to be small, on the order of 5%. The extreme case would be a 10% difference (eg, 85% RFS for one and 95% RFS for the other). Based on available experience and peer-reviewed literature, it is not likely that, for small tumors (ie, T1a) the 5-year local RFS for cryoablation or RF ablation is any lower than 85% (7–10,13–16). To perform a randomized trial to
Gervais
’
JVIR
assess a difference in RFS for T1a renal tumors for RF ablation versus cryoablation, one would seek statistical significance with a P value of .05 and statistical power of 0.80. To estimate the sample size needed for such a study, one would estimate the expected difference between the two modalities. Based on the available evidence, any such difference is likely in the range of 0%–10%. With these parameters, estimated sample size for a trial seeking a 5% RFS difference, eg, 90% for ablation modality A and 95% for ablation modality B, would be 465 patients in each arm, for a total of 930 patients (17). For a more extreme difference of 10% (0.85 vs 0.95), the sample size would decrease to 152 patients in each arm, or a total of 304 patients (17). What does all this mean? The performance of a randomized trial to detect a possible, undoubtedly small, difference between cryoablation and RF ablation in the treatment of T1a renal tumors may require more than 900 patients. Enrollment of this many patients would require a multiinstitutional trial performed over the course of many years. Such a trial has proved elusive for other reasons. Device companies are typically much smaller than pharmaceutical companies and have fewer resources available to fund such studies. A relatively rare cancer with a high survival rate with the use of existing surgical techniques further limits the number of patients who fit existing guidelines for ablation of RCC. Excellent survival with existing therapies limits the interest of government agencies in funding such trials. Finally, with RF ablation and cryoablation technology widely available in most tertiary-care centers and increasingly available outside of tertiary-care settings, patients eligible for renal tumor ablation can opt for ablation without being involved in research studies. The concepts in the exercise described and conclusions illustrated hold true in the comparison of any pair of modalities, not only for RF ablation compared with cryoablation. The same can be applied in the future to compare RF ablation or cryoablation versus MW ablation or IRE if and when sufficient 5-year RFS data become available. A small number of early reports of MW ablation for small renal appearance present technical effectiveness and RFS rates similar to those of RF ablation and cryoablation. This suggests again that, if there is a difference in RFS between MW ablation and RF ablation or cryoablation, it will likely be small, so the effect of changing modality would require a large sample size to detect.
TECHNOLOGY ENHANCEMENTS, NEW TECHNOLOGIES, AND OTHER OPEN QUESTIONS It can be argued that RF ablation and cryoablation technology are fairly mature. Failures to achieve complete necrosis in early studies may have been in part
Volume 24
’
Number 8
’
August
’
2013
related to a learning-curve effect. In current practice, most T1a tumors can be completely treated with RF ablation or cryoablation in a single session. MW technology is in evolution with multiple devices currently in the United States and world markets. It is likely that the next few years will see consolidation of some of these device companies. The question of which device is better will remain. Even if a small difference in local RFS rates were demonstrated for different renal cancer ablation modalities in a large multicenter prospective randomized study, the question remains as to whether such a difference would matter clinically. For example, a 3% difference in 5-year RFS between RF ablation and cryoablation, if it exists, is likely of no real clinical significance. It could be argued that even a 5% difference would be of little practical significance because, for such a small difference (90% vs 95%), physicians are likely to continue to base the choice of ablation modality for small renal masses on other parameters or preferences. These include but are not limited to operator experience with a preferred modality, technical effectiveness in a single session, and cost of maintaining multiple systems (equipment, infrastructure, operator and facility familiarity). For such small differences in local RFS, these other considerations enter the decision-making process and assume a more prominent role. Operator familiarity with multiple systems is facilitated in centers with larger case volumes. Operators who treat few cases per year will likely prefer a single system even if different modalities have advantages in different situations. Finally, a small difference in RFS between RF ablation and cryoablation, if it exists, may be of little concern if repeat ablation proves successful in the treatment of many recurrences.
QUESTIONS FOR THE FUTURE Given the challenges inherent in comparing RF ablation and cryoablation of small RCC in a randomized trial, new knowledge will most likely continue to emerge from cohort studies as well as from multicenter registries. With this in mind, the Society of Interventional Radiology supported a consensus panel for renal ablation protocol development in 2010. The recommendations included the development of registries (18). In the past 2 years, a renal tumor ablation registry has been developed and has enlisted centers and accrued cases. It will likely be a few more years before ablation modality–specific questions can be attempted to be addressed. Such large databases will help, but will never provide an answer that is purely the result of different technologies, as operator experience and other local variations will influence outcomes because of the absence of prospective randomization. From a quality assurance perspective, the effectiveness may be different depending
1137
on operator experience with tumor ablation with each individual technology. Nevertheless, although the question of which technology is better may remain unanswered, data-driven quality benchmarks may be developed by using such registries. Such benchmarks can establish a minimum level of recurrence rates and complication rates expected for small renal masses. If those targets can be achieved with RF ablation, cryoablation, MW ablation, or whatever new technology the future brings, a new baseline of expected performance can be defined as new operators and technologies become integrated into the practice of interventional oncology. Although registries will increase our knowledge, they too are subject to limitations of the existing literature. Cryoablation and RF ablation ablation have recognized advantages and disadvantages, and case selection biases have developed based on experience rather than prospective randomized evaluation (19). Without any prospective trials, selection bias in practice favors cryoablation for masses larger than 3.0–3.7 cm and central masses and RF ablation for smaller posterior tumors. Cryoablation is often found to be more time-consuming and may result in greater bleeding risks. As a result of these practice patterns, bias in case selection will likely never be eliminated in any study. In summary, given the available peer-reviewed literature, it is likely that, if any real difference exists in local RFS between cryoablation and RF ablation for T1a renal tumors, it is likely to be small (5% or less) and would require a large multiinstitutional randomized trial to detect. Given the current widespread access to these ablation devices, the limited financial resources of device companies to support such trials, the time required for such a trial to accrue patients, and the development of new technology over such time periods, such a trial is not likely to be developed or completed. Moreover, such a small difference may not impact operator choices in choosing ablation equipment. Case selection bias in the existing literature and in current practice continues to constrain attempts to compare cryoablation and RF ablation in a completely unbiased manner. With these limitations, new knowledge and understanding will require assessment of 10-year recurrence rates and enrollment in registries.
REFERENCES 1. Zlotta AR, Wildschutz T, Raviv G, et al. Radiofrequency interstitial tumor ablation (RITA) is a possible new modality for treatment of renal cancer: ex vivo and in vivo experience. J Endourol 1997; 11:251–258. 2. McGovern FJ, Wood BJ, Goldberg SN, Mueller PR. Radio frequency ablation of renal cell carcinoma via image guided needle electrodes. J Urol 1999; 161:599–600. 3. Gervais DA, McGovern FJ, Arellano RS, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma: part 1, Indications,
1138
4.
5.
6.
7.
8. 9.
10.
11.
’
Commentary: Cryoablation vs RF Ablation for Renal Tumors
results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol 2005; 185:64–71. Silverman SG, Tuncali K, vanSonnenberg E, et al. Renal tumors: MR imaging-guided percutaneous cryotherapy—initial experience in 23 patients. Radiology 2005; 236:716–724. Zagoria RJ, Hawkins AD, Clark PE, et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR Am J Roentgenol 2004; 183:201–207. Choueiri TK, Schutz FA, Hevelone ND, et al. Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) database analysis. Urology 2011; 78:93–98. Hui GC, Tuncali K, Tatli S, Morrison PR, Silverman SG. Comparison of percutaneous and surgical approaches to renal tumor ablation: metaanalysis of effectiveness and complication rates. J Vasc Interv Radiol 2008; 19:1311–1320. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer 2008;113: 2671–1280. 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; 110:510–516. Psutka SP, Feldman AS, McDougal WS, McGovern FJ, Mueller P, Gervais DA. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol 2013; 63:486–492. Lane BR, Campbell SC, Gill IS. 10-year oncological outcomes after laparoscopic and open partial nephrectomy. J Urol 2013, http://dx.doi.org/ 10.1016/j.juro.2012.12.102.
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’
JVIR
12. Campbell SC, Novick AC, Belldegrun A, et al. Practice Guidelines Committee of the American Urological Association. Guideline for management of the clinical T1 renal mass. J Urol 2009; 182:1271–1279. 13. Aron M, Kamoi K, Remer E, Berger A, Desai M, Gill I. Laparoscopic renal cryoablation: 8-year, single surgeon outcomes. J Urol 2010; 183: 889–895. 14. Best SL, Park SK, Yaacoub RF, et al. Long-term outcomes of renal tumor radio frequency ablation stratified by tumor diameter: size matters. J Urol 2012; 187:1183–1189. 15. Goyal J, Verma P, Sidana A, Georgiades CS, Rodriguez R. Single-center comparative oncologic outcomes of surgical and percutaneous cryoablation for treatment of renal tumors. J Endourol 2012; 26:1413–1429. 16. Derweesh IH, Malcolm JB, Diblasio CJ, et al. Single center comparison of laparoscopic cryoablation and CT-guided percutaneous cryoablation for renal tumors. J Endourol 2008; 22:2461–2467. 17. Schoenfeld DA. Statistical considerations for clinical trials and scientific experiments. Available at http://www.hedwig.mgh.harvard.edu/sample_ size/size.html Accessed April 30, 2013. 18. Georgiades CS, Rodriguez R, Littrup PJ, et al. Development of a research agenda for percutaneous renal tumor ablation: proceedings from a multidisciplinary research consensus panel. J Vasc Interv Radiol 2010; 21:1807–1816. 19. 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; 200:461–466.
Cryoablation versus Radiofrequency Ablation for Renal Tumor Ablation: Time to Reassess? Debra A. Gervais, MD ABBREVIATIONS IRE = irreversible electroporation, MW = microwave, RCC = renal cell carcinoma, RF = radiofrequency
Of the widely available methods for renal tumor ablation, cryoablation was the first to be assessed in the treatment of renal cell carcinoma (RCC) by using open surgical approaches. Open surgical access was necessary because early cryoprobes were too large for percutaneous application. Initial evaluation of percutaneous approaches to renal tumor ablation in humans included a “treat-and-resect” case reported by Zlotta et al (1) in 1997 and the first case with ablation as the sole planned treatment reported by McGovern et al (2) in 1999. With the advent of percutaneous needle applicators, renal tumor ablation moved to interventional radiology suites with ultrasound (US), computed tomography, and, in some cases, magnetic resonance imaging guidance. With percutaneous cryoprobes available shortly thereafter, the next several years saw expansion of the use of percutaneous image-guided radiofrequency (RF) ablation and cryoablation of renal tumors. Most recently, newer modalities such as microwave (MW) ablation and irreversible electroporation (IRE) have been assessed, and even promoted by some, to treat small tumors. The appeal of percutaneous needle applicators for tumor ablation was the avoidance of surgery in selected patients. Indications for renal tumor ablation include advanced age, multiple comorbid conditions, solitary kidneys, familial syndromes, or multiple sporadic RCC. Early experience with small tumors showed a high technical effectiveness rate with a low recurrence rate over short follow-up intervals (3–5). These early successes led to growing enthusiasm for its use in growing numbers of patients, as documented by a Surveillance, Epidemiology, and End Results database trend evaluation comparing the From the Department of Radiology, Abdominal Imaging and Intervention, Massachusetts General Hospital, White 270, 55 Fruit St., Boston, MA 02114. Received May 6, 2013; final revision received and accepted May 11, 2013. Address correspondence to D.A.G.; E-mail: [email protected] D.A.G. has received Massachusetts).
a
research
grant
& SIR, 2013 J Vasc Interv Radiol 2013; 24:1135–1138 http://dx.doi.org/10.1016/j.jvir.2013.05.030
from
Covidien
(Mansfield,
use of radical nephrectomy, partial nephrectomy, and tumor ablation between 2004 and 2007 (6). What was also clear from early experience is that tumor size matters for almost any measure of therapy effectiveness. For small tumors measuring 4 cm or less (ie, T1a), cryoablation and RF ablation showed technical effectiveness rates in the range of 87% to 97% in cohorts with short follow-up periods (7–10). What has not been assessed in randomized trials is comparative effectiveness of RF ablation and cryoablation. With the advent of new devices on the market such as those used to perform MW ablation and IRE, the question of which ablation method is optimal for RCC not only persists but garners new attention. The peerreviewed literature consists of an ever-increasing number of cohort studies with varying protocols for tissue diagnosis, follow-up, and method of ablation.
WHICH IS BETTER FOR SMALL RENAL MASSES: RF ABLATION OR CRYOABLATION? For practices with cryoablation and RF ablation systems or for practices seeking to purchase a first ablation system, the question is often phrased as, “Which is better for small renal masses: RF ablation or cryoablation?” A number of factors contribute to the difficulty in developing randomized trials to answer this question. Among the major drivers are the following challenges: (i) existing extirpative therapies for T1a renal tumors such as complete nephrectomy or partial nephrectomy are associated with high local recurrence-free survival (RFS) and disease-free survival rates (11); (ii) accumulated evidence suggests that any difference in RFS between RF ablation and cryoablation, if any such difference exists, is likely to be very small (7–10); and (iii) given the success of extirpative therapies, existing guidelines recommend tumor resection as a standard therapy with ablation as an option for a smaller number of selected patients (12).
1136
’
Commentary: Cryoablation vs RF Ablation for Renal Tumors
To seek an answer comparing RF ablation and cryoablation performance in the treatment of RCC requires the question to be defined with a more measurable parameter. For partial nephrectomy, 5-year RFS rates are higher than 97% (11). Newer percutaneous modalities are therefore held to a very high standard. Any meaningful survival data must include 5-year RFS. For new procedures, 5-year survival means, at a minimum, that studies must accrue and follow up patients for 5 years and sometimes more, even though Kaplan–Meier log-rank tests adjust for some patients to enter into the study for shorter periods of time than the interval studied. Published reports with 5-year RFS have appeared for RF ablation and cryoablation in recent years (10,13–16). For cryoablation, reports include laparoscopic and percutaneous cryoablation as a result of the earlier adoption of cryoablation via surgical approaches. That now leaves in a current state with a tumor that has an excellent prognosis of 97% 5-year disease free survival after extirpative therapy and growing data on two ablation modalities with 5-year disease-free survival rates in the range of 87%–97%. Although RFS after partial nephrectomy is better than after tumor ablation, the gap in the 5-year RFS rates between surgery and best reported ablation results is small. In addition, the 5-year RFS ranges for cryoablation and RF ablation overlap substantially. Proponents of each side debate the relative merits of each ablation modality in panels with no clear data-driven consensus, but with proponents arguing for a small incremental gain in their preferred method of treatment by selecting reports that favor their favored modality. Neither side has sufficient data to provide a definitive and final answer. What do existing reports tell us about RFS after cryoablation and RF ablation of small renal masses? Any difference in RFS between cryoablation and RF ablation for the treatment of T1a RCC is nonexistent or very small. Two metaanalyses reached different conclusions (8,9) regarding effectiveness but did not specifically compare 5-year RFS. Kunkle and Uzzo (8) reported local progression rates of 12.9% versus 5.2% for RF ablation and cryoablation, respectively. In contrast, El Dib et al (9) reported 90% and 89% effectiveness for RF ablation and cryoablation, respectively, with no statistically significant difference, and concluded that it is urgent to perform trials with long-term data to determine whether RF ablation or cryoablation is better. How to go about assessing such a difference for those who believe it exists will be illustrated next. Any real difference in RFS is likely to be small, on the order of 5%. The extreme case would be a 10% difference (eg, 85% RFS for one and 95% RFS for the other). Based on available experience and peer-reviewed literature, it is not likely that, for small tumors (ie, T1a) the 5-year local RFS for cryoablation or RF ablation is any lower than 85% (7–10,13–16). To perform a randomized trial to
Gervais
’
JVIR
assess a difference in RFS for T1a renal tumors for RF ablation versus cryoablation, one would seek statistical significance with a P value of .05 and statistical power of 0.80. To estimate the sample size needed for such a study, one would estimate the expected difference between the two modalities. Based on the available evidence, any such difference is likely in the range of 0%–10%. With these parameters, estimated sample size for a trial seeking a 5% RFS difference, eg, 90% for ablation modality A and 95% for ablation modality B, would be 465 patients in each arm, for a total of 930 patients (17). For a more extreme difference of 10% (0.85 vs 0.95), the sample size would decrease to 152 patients in each arm, or a total of 304 patients (17). What does all this mean? The performance of a randomized trial to detect a possible, undoubtedly small, difference between cryoablation and RF ablation in the treatment of T1a renal tumors may require more than 900 patients. Enrollment of this many patients would require a multiinstitutional trial performed over the course of many years. Such a trial has proved elusive for other reasons. Device companies are typically much smaller than pharmaceutical companies and have fewer resources available to fund such studies. A relatively rare cancer with a high survival rate with the use of existing surgical techniques further limits the number of patients who fit existing guidelines for ablation of RCC. Excellent survival with existing therapies limits the interest of government agencies in funding such trials. Finally, with RF ablation and cryoablation technology widely available in most tertiary-care centers and increasingly available outside of tertiary-care settings, patients eligible for renal tumor ablation can opt for ablation without being involved in research studies. The concepts in the exercise described and conclusions illustrated hold true in the comparison of any pair of modalities, not only for RF ablation compared with cryoablation. The same can be applied in the future to compare RF ablation or cryoablation versus MW ablation or IRE if and when sufficient 5-year RFS data become available. A small number of early reports of MW ablation for small renal appearance present technical effectiveness and RFS rates similar to those of RF ablation and cryoablation. This suggests again that, if there is a difference in RFS between MW ablation and RF ablation or cryoablation, it will likely be small, so the effect of changing modality would require a large sample size to detect.
TECHNOLOGY ENHANCEMENTS, NEW TECHNOLOGIES, AND OTHER OPEN QUESTIONS It can be argued that RF ablation and cryoablation technology are fairly mature. Failures to achieve complete necrosis in early studies may have been in part
Volume 24
’
Number 8
’
August
’
2013
related to a learning-curve effect. In current practice, most T1a tumors can be completely treated with RF ablation or cryoablation in a single session. MW technology is in evolution with multiple devices currently in the United States and world markets. It is likely that the next few years will see consolidation of some of these device companies. The question of which device is better will remain. Even if a small difference in local RFS rates were demonstrated for different renal cancer ablation modalities in a large multicenter prospective randomized study, the question remains as to whether such a difference would matter clinically. For example, a 3% difference in 5-year RFS between RF ablation and cryoablation, if it exists, is likely of no real clinical significance. It could be argued that even a 5% difference would be of little practical significance because, for such a small difference (90% vs 95%), physicians are likely to continue to base the choice of ablation modality for small renal masses on other parameters or preferences. These include but are not limited to operator experience with a preferred modality, technical effectiveness in a single session, and cost of maintaining multiple systems (equipment, infrastructure, operator and facility familiarity). For such small differences in local RFS, these other considerations enter the decision-making process and assume a more prominent role. Operator familiarity with multiple systems is facilitated in centers with larger case volumes. Operators who treat few cases per year will likely prefer a single system even if different modalities have advantages in different situations. Finally, a small difference in RFS between RF ablation and cryoablation, if it exists, may be of little concern if repeat ablation proves successful in the treatment of many recurrences.
QUESTIONS FOR THE FUTURE Given the challenges inherent in comparing RF ablation and cryoablation of small RCC in a randomized trial, new knowledge will most likely continue to emerge from cohort studies as well as from multicenter registries. With this in mind, the Society of Interventional Radiology supported a consensus panel for renal ablation protocol development in 2010. The recommendations included the development of registries (18). In the past 2 years, a renal tumor ablation registry has been developed and has enlisted centers and accrued cases. It will likely be a few more years before ablation modality–specific questions can be attempted to be addressed. Such large databases will help, but will never provide an answer that is purely the result of different technologies, as operator experience and other local variations will influence outcomes because of the absence of prospective randomization. From a quality assurance perspective, the effectiveness may be different depending
1137
on operator experience with tumor ablation with each individual technology. Nevertheless, although the question of which technology is better may remain unanswered, data-driven quality benchmarks may be developed by using such registries. Such benchmarks can establish a minimum level of recurrence rates and complication rates expected for small renal masses. If those targets can be achieved with RF ablation, cryoablation, MW ablation, or whatever new technology the future brings, a new baseline of expected performance can be defined as new operators and technologies become integrated into the practice of interventional oncology. Although registries will increase our knowledge, they too are subject to limitations of the existing literature. Cryoablation and RF ablation ablation have recognized advantages and disadvantages, and case selection biases have developed based on experience rather than prospective randomized evaluation (19). Without any prospective trials, selection bias in practice favors cryoablation for masses larger than 3.0–3.7 cm and central masses and RF ablation for smaller posterior tumors. Cryoablation is often found to be more time-consuming and may result in greater bleeding risks. As a result of these practice patterns, bias in case selection will likely never be eliminated in any study. In summary, given the available peer-reviewed literature, it is likely that, if any real difference exists in local RFS between cryoablation and RF ablation for T1a renal tumors, it is likely to be small (5% or less) and would require a large multiinstitutional randomized trial to detect. Given the current widespread access to these ablation devices, the limited financial resources of device companies to support such trials, the time required for such a trial to accrue patients, and the development of new technology over such time periods, such a trial is not likely to be developed or completed. Moreover, such a small difference may not impact operator choices in choosing ablation equipment. Case selection bias in the existing literature and in current practice continues to constrain attempts to compare cryoablation and RF ablation in a completely unbiased manner. With these limitations, new knowledge and understanding will require assessment of 10-year recurrence rates and enrollment in registries.
REFERENCES 1. Zlotta AR, Wildschutz T, Raviv G, et al. Radiofrequency interstitial tumor ablation (RITA) is a possible new modality for treatment of renal cancer: ex vivo and in vivo experience. J Endourol 1997; 11:251–258. 2. McGovern FJ, Wood BJ, Goldberg SN, Mueller PR. Radio frequency ablation of renal cell carcinoma via image guided needle electrodes. J Urol 1999; 161:599–600. 3. Gervais DA, McGovern FJ, Arellano RS, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma: part 1, Indications,
1138
4.
5.
6.
7.
8. 9.
10.
11.
’
Commentary: Cryoablation vs RF Ablation for Renal Tumors
results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol 2005; 185:64–71. Silverman SG, Tuncali K, vanSonnenberg E, et al. Renal tumors: MR imaging-guided percutaneous cryotherapy—initial experience in 23 patients. Radiology 2005; 236:716–724. Zagoria RJ, Hawkins AD, Clark PE, et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR Am J Roentgenol 2004; 183:201–207. Choueiri TK, Schutz FA, Hevelone ND, et al. Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) database analysis. Urology 2011; 78:93–98. Hui GC, Tuncali K, Tatli S, Morrison PR, Silverman SG. Comparison of percutaneous and surgical approaches to renal tumor ablation: metaanalysis of effectiveness and complication rates. J Vasc Interv Radiol 2008; 19:1311–1320. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer 2008;113: 2671–1280. 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; 110:510–516. Psutka SP, Feldman AS, McDougal WS, McGovern FJ, Mueller P, Gervais DA. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol 2013; 63:486–492. Lane BR, Campbell SC, Gill IS. 10-year oncological outcomes after laparoscopic and open partial nephrectomy. J Urol 2013, http://dx.doi.org/ 10.1016/j.juro.2012.12.102.
Gervais
’
JVIR
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