The outcomes of radiofrequency ablation (RFA) procedures in more than 550 patients with a total of nearly 700 lesions have been described in 21 uncontrolled studies. The characteristics of the patients and RFA procedures varied widely within and across the studies in terms of tumor type (e.g., exophytic, parenchymal, central, with or without history of von Hipple-Lindau disease), tumor size (from less than 1 cm to over 8 cm), length of follow-up (from less than one month to 48 months), imaging modality used for guidance, and reason for using RFA. Overall, 88%–100% of procedures were considered successful shortly after one or two ablations (i.e., no signs of residual tumor by histologic analysis after excision or by post-RFA radiologic imaging). Significant but nonfatal complications were reported in 8%–13% of patients in seven studies, including perinephric hematomas, hemorrhage, and ureteral strictures.
In general, available data were inadequate or lacked appropriate statistical analyses to estimate duration of survival or quality of life. Follow-up duration in most studies was insufficient to determine recurrence rates after RFA from viable tumor cells remaining in situ at ablation sites. A particular concern with the available data is that patient selection criteria and rationale for using RFA were not well described or did not provide a compelling argument to use the technique in lieu of potentially curative surgical resection or extirpation. In total, the available evidence was insufficient to permit conclusions on net health outcomes of RFA for renal cancers.
Additional information is available in recent review articles.
Stern and colleagues retrospectively compared patients with stage T1a renal tumors, confirmed by pathology to be renal cell carcinoma (RCC), treated with either partial nephrectomy (n=34) or RFA (n=34). The mean follow-up for the partial nephrectomy group was 47 months (range: 24–93) and for the RFA group 30 months (range: 18–42). Three-year recurrence-free survival rate was 95.2% for partial nephrectomy and 91.4% for RFA (p=0.58). There were no disease-specific deaths in either group. In this small study, intermediate outcomes for patients with T1a RCCs were similar whether treated with partial nephrectomy or RFA.
A review article summarizes the literature from the last five years, which includes 713 patients who underwent RFA of 866 renal tumors with an average follow-up of 12.6 months. The average tumor-free survival rate was 85.4%. The author notes that across different study reports there are significant variations in the practice of RFA for kidney tumors—including the types of devices used, imaging modality and performance experience—making it difficult to compare results across studies. Additionally, the article points out that the longest average follow-up of published studies of RFA and kidney tumors is 28 months, and that long-term follow-up data are necessary to validate the use of this technique.
Kunkle and Uzzo conducted a comparative meta-analysis evaluating cryoablation and RFA as primary treatment for small renal masses. Forty-seven case series representing 1375 renal tumors were analyzed. Of 600 lesions treated with cryoablation, 494 were biopsied before treatment vs. 482 of 775 treated with RFA. The incidence of RCC with known pathology was 71.7% in the cryoablation group and 90% in the RFA group. The mean duration of follow-up after RFA was 15.8 months. Local tumor progression was reported in 31 of 600 lesions after cryoablation and in 100 of 775 lesions after RFA, a difference that was significant (p<0.0001). Progression to metastatic disease was described in 6 of 600 lesions after cryoablation vs. 19 of 775 after RFA (p=0.06). The authors caution that minimally invasive ablation generally has been performed selectively on older patients with smaller tumors, possibly resulting in selection bias; series of ablated lesions tend to have shorter post-treatment follow-up compared with tumors managed by surgical excision or active surveillance; and treatment efficacy may be overestimated in series that include tumors with unknown pathology.
In summary, based on the scientific data (large numbers of patients treated with follow-up) and the clinical guidelines discussed below, RFA of small renal cancers may be considered medically necessary in those patients who are not surgical candidates due to comorbid conditions or who have baseline renal insufficiency such that standard surgical procedures would impair their kidney function.
The National Comprehensive Cancer Network (NCCN) 2010 Guidelines have added the statement that ”emerging energy ablative techniques (e.g., cryosurgery or RFA) are currently considered an option by some experts for selected small tumors although a rigorous comparison with surgical resection (i.e., total or partial nephrectomy by open or laparoscopic techniques) has not been done.”
In the National Cancer Institute Clinical Trials Database (PDQ®), one ongoing Phase II/III trial is identified that compares surgery and RFA for the treatment of renal tumors (NCT00221728). The study design is open label and randomized with expected enrollment of 180 patients from nine centers. Patients are eligible if they have a kidney tumor smaller than 4 cm, confined to the kidney (T1a). Principal outcome is five-year efficacy measured as no residual tumor and no recurrence at the site of treatment. The estimated study completion date is April 2011.
National Institute for Clinical Excellence (NICE) issued a Guidance in 2004 in which they indicate that “limited evidence suggests that percutaneous radiofrequency ablation (RFA) of renal cancer brings about reduction of tumour bulk and that the procedure is adequately safe. However, the evidence of its effect on symptom control and survival is not yet adequate to support the use of this procedure without special arrangements for consent and for audit or research” and that ”the procedure should normally be limited to patients who are unsuitable for surgery”.
In 2010, Salas and colleagues reviewed 17 studies identified from literature published between 2003 and 2009. The authors found RFA has proven to demonstrate oncologic outcomes that are almost equivalent to surgical resection when treating renal tumors with a mean size less than 4.0 cm. Renal function also declines minimally and is significantly lower than surgical resection. Van Poppel et al. also conducted a review of the literature published between 2004 and May 2011. In this review, the authors concluded RFA is a reasonable treatment option for most low-grade renal tumors less than 4 cm in patients who are not candidates for surgical resection or active surveillance. The authors noted the need for long-term prospective studies to compare ablative techniques for renal ablation, such as RFA versus cryoablation.
Based on the scientific data (large numbers of patients treated with follow-up), RFA of small (i.e., 4 cm or less) renal cancers may be considered medically necessary in those patients who are not surgical candidates due to comorbid conditions or who have baseline renal insufficiency such that standard surgical procedures would impair their kidney function. In addition, updated 2012 NCCN guidelines indicate RFA is a thermal ablation option for the treatment of kidney cancer in select patients such as elderly patients and others with competing health risks.
In a 2010 Cochrane review, Nabi and colleagues review the evidence on the management of localized RCC. No randomized trials comparing cryoablation to open radical or partial nephrectomy were identified. One nonrandomized study compared laparoscopic partial nephrectomy with laparoscopic cryoablation using a matched paired-analysis (O’Malley et al.) and three retrospective studies. The review notes percutaneous cryoablation can successfully destroy small RCC and may be considered a treatment option in patients with serious comorbidities that pose surgical risks. The review concluded that high quality, randomized controlled trials (RCTs) are required in the management of localized RCC and that one area of emphasis should be the role of renal surgery compared to minimally invasive techniques for small tumors (<4 cm).
Long et al. reported on a 2011 systematic review comparing percutaneous cryoablation to surgical cryoablation of small renal masses. A total of 42 studies treating small renal masses (pooled total of 1,447 lesions) were reviewed including 28 articles on surgical cryoablation and 14 articles on percutaneous cryoablation. The authors concluded percutaneous and surgical cryoablation for small renal masses have similar, acceptable short-term oncologic outcomes, and each technique is relatively equivalent. Long-term data are needed to ultimately compare ablation techniques to the gold standard of partial or radical nephrectomy.
Kunkle and Uzzo conducted a comparative meta-analysis evaluating cryoablation and RFA as primary treatment for small renal masses. Forty-seven case series representing 1,375 renal tumors were analyzed. Of 600 lesions treated with cryoablation, 494 were biopsied before treatment versus 482 of 775 treated with RFA. The incidence of RCC with known pathology was 72% in the cryoablation group and 90% in the RFA group. The mean duration of follow-up after cryoablation was 22.5 months. Most studies used contrast enhanced imaging to determine treatment effect. Local tumor progression was reported in 31 of 600 (5%) lesions after cryoablation and in 100 of 775 (13%) lesions after RFA. Progression to metastatic disease was described in 6 of 600 (1%) lesions after cryoablation versus 19 of 775 (2.5%) after RFA. The authors caution that minimally invasive ablation generally has been performed selectively on older patients with smaller tumors, possibly resulting in selection bias; series of ablated lesions tend to have shorter post-treatment follow-up compared with tumors managed by surgical excision or active surveillance; and treatment efficacy may be overestimated in series that include tumors with unknown pathology.
A number of studies reported intermediate term outcomes for cryoablation with RCC. Weld and colleagues reported on three-year follow-up of 36 renal tumors (22 were malignant) treated with laparoscopic cryoablation. In this series, the three-year cancer-specific survival rate was 100%, and no patient developed metastatic disease. The authors concluded that these intermediate-term data seemed equivalent to results obtained with extirpative therapy. Hegarty and co-workers reported results on 164 laparoscopic cryoablations and 82 percutaneous RFAs for localized renal tumors. Mean tumor size was 2.5 cm. Cancer-specific survival following cryotherapy was 98% at a median follow-up of three years and 100% for RFA at just one year median follow-up. The authors noted that cryoablation and RFA are developmental nephron-sparing options and that early results are encouraging in terms of early oncologic control, preservation of renal function, and low complication rates. Studies are also reporting results with small numbers of patients comparing laparoscopic cryoablation with laparoscopic partial nephrectomy for treatment of renal masses (O’Malley et al.).
Matin and Ahrar reviewed studies of cryoablation and RFA with at least 12-month follow-up and found that recently published three- and five-year outcomes show 93–98% cancer-specific survival in small cohorts. They caution that, while studies suggest satisfactory outcomes, given the limitations of imaging and the indolent nature of the tumors, stringent selection criteria and rigorous follow-up is required.
Strom and colleagues reported on a retrospective comparison of 145 patients who underwent laparoscopic (n=84) or percutaneous (n=61) cryoablation of small renal masses at five academic medical centers in the United States. These patients were offered cryoablation because they were considered to be at higher risk for complications from partial nephrectomy or were not surgical candidates due to comorbidities. Mean tumor size was 2.7 cm in the laparoscopic group versus 2.5 cm in the percutaneous group. Patients were followed for a longer period of time in the laparoscopic group (mean of 42.3 + 21.2 months) compared to the percutaneous group (31.0 + 15.9 months [P=0.008]). Complications in both treatment groups were similar and did not occur with any significant difference in frequency. At a mean intermediate follow-up of 37.6 months, local tumor recurrence was significantly more frequent in the percutaneous group at 16.4% (10/61) compared to 5.9% (5/84) in the laparoscopic group. However, disease-free survival and overall survival were not significantly different at last follow-up in the laparoscopic group compared to the percutaneous group (91.7% and 89.3% vs. 93.7% and 88.9%, respectively).
In a prospective, single institution study, Rodriguez et al. reported on 113 patients consecutively treated with percutaneous cryoablation for 117 renal lesions. The average size of renal lesions in the study was 2.7 + 2.4 cm (83 or 71% were RCC). Patients were selected for cryoablation over surgery when tumors were equal to or less than 4 cm and percutaneously approachable or if the patient could not tolerate surgery when tumors were greater than 4–7 cm. Technical success was reported to be 100% with 93% of patients having no complications or only mild complications. At a median follow-up of two years with 59 patients, efficacy was 98.3% and 92.3% at three years with 13 patients. Metastatic disease did not occur in any of the patients during the follow-up period, and cancer specific survival was 100%.
Nguyen et al. evaluated options for salvage of ipsilateral tumor recurrence after previous ablation. Recurrence rates at their center were 13 of 175 (7%) after cryoablation and 26 of 104 (25%) after RFA. Extensive perinephric scarring was encountered in all salvage operations following cryoablation, and the authors conclude that cryoablation in particular can lead to extensive perinephric fibrosis, which can complicate attempts at salvage.
An online search of ClinicalTrials.gov in February 2012 found no randomized controlled trials. NCT01117779, Tracking Renal Tumors After Cryoablation Evaluation (TRACE) Registry is an observational, open-label, single-arm, multi-center registry of subjects who have undergone renal lesion cryoablation per their physician's standard of care. This registry is currently accepting participants. Subjects will be observed for five years from the date of their cryoablation procedure. Several other trials are currently accepting participants.
The 2009 guidelines from the American Urological Association on stage one renal masses indicate percutaneous or laparoscopic cryoablation “is an available treatment option for the patient at high surgical risk who wants active treatment and accepts the need for long-term radiographic surveillance after treatment. The guidelines also indicate cryoablation “should be discussed as a less-invasive treatment option” in healthy patients with a renal mass equal to or less than 4.0 cm and clinical stage T1a. Patients should be informed that “local tumor recurrence is more likely than with surgical excision, measures of success are not well defined, and surgical salvage may be difficult.” These recommendations are based on review of the data and “appreciable” majority consensus.
The National Comprehensive Cancer Network (NCCN) practice guidelines for kidney cancer state that based on lower level evidence and uniform NCCN consensus, cryosurgery “can be considered for patients with clinical stage T1 renal lesions who are not surgical candidates. Biopsy of small lesions may be considered to obtain or confirm a diagnosis of malignancy and guide surveillance, cryosurgery … [and] ablation strategies.” The NCCN guidelines also note “rigorous comparison with surgical resection (i.e., total or partial nephrectomy by open or laparoscopic techniques) has not been done and [t]hermal ablative techniques are associated with a higher local recurrence rate than conventional surgery.”
The literature on the use of cryosurgical ablation of RCC tumors consists primarily of reports of single-center case series; however, evidence is accumulating that cryoablation provides short-term tumor control and perhaps survival benefit for carefully selected patients with small RCCs, including for palliative treatment of inoperable tumor(s); cases where preservation of kidney function is critical; or patients who have failed, or are a poor candidate for, standard treatment such as surgical intervention, radiation, chemotherapy, or opioids.