Version May 2024
INTRODUCTION — The average size of a renal cell carcinoma (RCC) at presentation is decreasing, and more patients are presenting with small, localized lesions. In addition, there is an increasing awareness of the importance of preserving renal function, if this can be accomplished without compromising the oncologic outcome. (See "Diagnostic approach, differential diagnosis, and management of a small renal mass" and "Definitive surgical management of renal cell carcinoma", section on 'Partial nephrectomy'.)
Various ablative techniques as well as their indications and outcomes for patients with RCC are presented here. The surgical management and systemic treatment of RCC are discussed separately.
●(See "Definitive surgical management of renal cell carcinoma".)
●(See "Overview of the treatment of renal cell carcinoma".)
●(See "Systemic therapy of advanced clear cell renal carcinoma".)
GENERAL PRINCIPLES — Radiofrequency ablation (RFA), cryoablation, or microwave ablation are techniques that create sharply delineated areas of very high or low temperatures. These temperature extremes are used to produce tumor cell death. Other emerging ablative technologies include stereotactic ablative body radiotherapy and non-thermal irreversible electroporation (IRE) [1-3]. These minimally invasive technologies are rapidly gaining acceptance in selected patients as alternatives to surgery for many tumors, including renal cell carcinoma.
The increasing acceptance of RFA and cryoablation for kidney tumors is based upon favorable outcomes in initial studies, a low incidence of serious complications, less immediate morbidity than with surgery, lower cost, and the ability to treat patients in the outpatient setting. Optimal application of these ablative techniques requires interventional radiologists and urologists who are experienced and skilled in the application of the technology.
The potential benefits of these ablative techniques must be balanced against the limited long-term comparative efficacy data [4-7]. In addition, patients should be counseled that multiple treatment sessions may be required because of difficulties in monitoring the extent of ablation, particularly for tumors greater than 4 cm in diameter. Furthermore, these ablative techniques may not be appropriate for large lesions or tumors near the renal hilum.
INDICATIONS — The indications for radiofrequency ablation (RFA) or cryoablation to treat renal cell carcinoma (RCC) have not been definitively established.
Factors that can lead to consideration of an ablative approach rather than surgery include:
●A small, incidentally detected RCC (ideally <4 cm in diameter and limited to the kidney). (See "Diagnostic approach, differential diagnosis, and management of a small renal mass".)
●A patient who is considered a poor surgical candidate, based upon older age or significant comorbidity.
●The need for nephron-sparing treatment as a way to postpone or avoid the need for chronic dialysis. This includes patients with chronic renal insufficiency, a single kidney, bilateral RCCs, or a genetic predisposition to multiple tumors (eg, von Hippel-Lindau syndrome). (See "Hereditary kidney cancer syndromes".)
For patients with one or more of these factors, RFA or cryoablation may be an attractive option since ablation may avoid the morbidity of surgery while offering an effective and potentially curative treatment option [8-13]. Tumor ablation may have an initial advantage over surgery for small RCC treatment because of the lower costs; however, more frequent imaging is required after ablation [14].
In addition to the application of these techniques for small RCCs, RFA and cryoablation may be useful in some patients with local tumor recurrence after nephrectomy, intractable tumor-related hematuria, tumor debulking in patients with metastatic disease, or in the management of symptomatic distant metastases from a primary kidney tumor [15].
Patient selection — Patients are usually evaluated by both a urologist and a radiologist prior to treatment. Imaging is used to define the extent of disease and the presence or absence of metastases. In addition, treatment planning requires pretreatment imaging that can be performed with ultrasound, magnetic resonance (MR), or computed tomography (CT) [15,16]. A pretreatment biopsy should always be performed, as imaging does not accurately differentiate benign from malignant disease [17-19]. In addition, systemic treatments for patients with advanced RCC are increasingly being based on tumor histology and other pathologic features.
Tumor size and location are the most important factors that govern whether RCCs can be successfully treated [20,21].
●In determining the volume to be treated, a 0.5 to 1.0 cm "ablation margin" surrounding the tumor is needed to ensure that the entire tumor is treated [15]. Since temperature gradients exponentially decrease with distance from the radiofrequency or cryoablation probe, large tumors pose a significant challenge. In general, tumors <4 cm in diameter are ideal. Most tumors <3 cm can be treated in a single session. Tumors between 3.0 and 4.0 cm in diameter can also be successfully treated, although multiple ablations may be required [20-28].
●Exophytic tumors are most amenable to ablation, since these are surrounded by heat-insulating perirenal fat with relatively little vascular tissue, which can draw heat away from tumor ("heat-sink" effect). As a result, large exophytic tumors as large as 4 cm are almost always successfully treated, with 70 percent or more requiring only a single session. Parenchymal tumors may be more difficult to treat. Centrally located tumors are the hardest to successfully ablate due to the heat-sink effect and have an increased risk of treatment failure.
Contraindications — Relative contraindications to RFA or cryoablation include:
●A life expectancy less than one year.
●The presence of distant metastases.
●Tumors >5 cm or tumors in the hilum or central collecting system are generally not candidates for ablation. For tumors in which treatment may cause thermal injury to the proximal ureter (resulting in urine extravasation and urinoma), an intraureteral stent is usually inserted prior to treatment.
Absolute contraindications include irreversible coagulopathies or severe medical instability.
Choice of ablative technique — Operator experience and comfort with any given technique is one of the most important determinants for achieving a good outcome, with many interventional radiologists preferring RFA and many urologists preferring cryoablation, based upon local familiarity with a given technique.
Both cryoablation and RFA demonstrate very high efficacy with limited complications, which has made a direct comparison challenging. The ability to conduct a randomized clinical trial comparing these treatment approaches is limited since the number of patients needed to demonstrate a significant difference is too high to be feasible [29]. (See 'RFA versus cryoablation' below.)
Preliminary outcomes for microwave have started to accumulate, with this modality also demonstrating high efficacy, but further evaluation and follow-up is required [9,30,31]. Until then, the choice of microwave technology is also based upon operator comfort and experience.
PROCEDURE — Successful percutaneous tumor ablation requires killing all viable malignant cells including a 5 to 10 mm "ablative" margin of surrounding tissue, while minimizing damage to adjacent normal kidney. The most extensively used techniques are radiofrequency ablation (RFA), cryoablation, and microwave ablation. Other techniques such as high-intensity focused ultrasound show some promise but are not widely used outside of experimental settings.
RFA, cryoablation, and microwave ablation are typically performed with a percutaneous approach. A percutaneous approach is generally preferred over surgical approaches, which is consistent with guidelines from the American Urological Association (AUA) [18]. When done percutaneously, these techniques are usually an outpatient procedure unless comorbid conditions require hospitalization or closer observation. Only conscious sedation is typically necessary for anesthesia, although some clinicians and patients prefer general anesthesia.
The patient is placed prone or lateral decubitus. After local anesthesia is applied, the applicator is percutaneously advanced into the center of the tumor under computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI) guidance. Heat or cold is then applied for approximately 5 to 20 minutes as dictated by the device maker's recommendations. Depending upon the size and location of the tumor, the applicator may need to be readjusted and additional treatments administered, or multiple applicators may need to be used simultaneously.
After the procedure, the patient is monitored for several hours, and discharged home with oral analgesics for post-procedural pain. Patients usually are able to resume full activity within a couple of days.
A laparoscopic approach is similar to other surgical laparoscopic procedures requiring general anesthesia, and image guidance is limited to small transducer ultrasonography. Most patients treated laparoscopically are hospitalized overnight, and there may be more post-procedural pain [32].
The choice of laparoscopic versus percutaneous approach is based mostly upon the local expertise. Laparoscopic ablation is typically performed by urologists, while percutaneous tumor ablation is typically performed by interventional radiologists. Therefore, local referral and practice pattern usually dictate the chosen approach.
The anatomic location of the tumor also influences the choice between a laparoscopic or percutaneous approach. For example, some centers prefer to treat tumors within a posterior location (eg, closer to the back) percutaneously because they are more technically challenging to treat laparoscopically than anterior lesions.
No randomized controlled comparison of the approaches has been performed, and retrospective comparative data have yielded inconclusive and sometimes mixed conclusions [33]. (See 'Percutaneous versus laparoscopic ablation' below.)
Radiofrequency ablation — RFA utilizes a high-frequency (460 to 500 kHz) alternating current that is delivered into the tumor through a thin needle (usually 21- to 14-gauge) that is electrically insulated except for its terminal 1 to 3 cm. The current produces resistive friction in the tissue that is converted into heat, analogous to heat production from an electrical resister in a circuit. Heat, in turn, causes cellular destruction and protein denaturation. Most RFA systems used for the kidney are monopolar, and the current is completed with grounding pads placed on the patient's back and thighs.
Efforts to increase tumor ablation have led to the development of various RF applicators, such as multi-tined applicators, cluster applicators, and pulsed energy delivery. There are multiple RFA devices available for soft tumor ablation. There is no demonstrated advantage of any one device.
Cryoablation — For cryoablation, liquid nitrogen or argon is introduced into a probe in a controlled fashion, resulting in freezing of the surrounding tissues, with the formation of an "ice ball" that can be visualized. Intracellular ice crystals disrupt the cell membrane and other intracellular activities, leading to cell death. Cells that are not directly killed may undergo apoptosis.
A typical cryoablation session involves freezing, thawing, and refreezing, which is particularly effective at mediating cellular disruption. The applicators initially developed for cryoablation were relatively large, and laparoscopy was required. Smaller applicators are now available, enabling percutaneous image-guided cryoablation.
During cryoablation, the ice ball can be visualized in real time with either CT or MRI, which allows the extent of cell death to be more reliably predicted. Complete cell death is thought to occur 3 mm inside the edge of the ice ball; thus, most operators extend the ice ball at least 5 mm beyond the tumor margin to ensure complete tumor coverage.
Microwave ablation — Microwave energy also uses heat for use in thermal ablation [34,35]. In contrast to RFA, a microwave incorporates an antenna to receive externally applied energy at 930 to 2450 mHz. This microwave energy results in rotation of polar molecules that is opposed by frictional forces, which is then converted to heat. Microwave ablation is becoming increasingly popular for ablation of liver and lung tumors, but data for use for renal cell carcinoma (RCC) are still limited. One meta-analysis comparing microwave ablation with cryoablation showed that both were effective and resulted in similar efficacy (93.8 versus 91.3 percent, respectively) and cancer-specific survival (98.3 versus 96.8 percent, respectively) [36]. Since cryoablation and RFA have already been established as effective methods, it is unlikely that any meaningful difference will be demonstrated without a large multi-institutional clinical trial [29].
A potential advantage of microwave ablation over RFA is greater energy deposition, particularly when tissue vaporization occurs, and thus the development of higher temperatures. The higher energy may also be more resilient to the heat-sink effect, which can be an important obstacle for RFA [37].
Emerging therapies
Stereotactic ablative body radiotherapy — Stereotactic ablative body radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is an emerging treatment option for select patients with primary locoregional RCC, including those with medically inoperable disease. Data from observational studies and early phase clinical trials suggest that SABR is well tolerated and can offer long-term local disease control in some patients [38-44]. Further randomized trials comparing SABR with standard treatment approaches, such as surgical resection and other ablative techniques, are necessary prior to integrating this technique into routine clinical practice.
Irreversible electroporation — Irreversible electroporation (IRE) is an emerging alternative [45]. However, IRE is also considered experimental because its efficacy and safety have not been established. The mid- and long-term outcomes are still unknown, but it may develop an indication for niche consideration [3,46-48].
IRE uses delivery of focal micro- to millisecond electrical pulses via thin needles to induce cell death by disrupting the cell membrane. Unlike RFA or microwave, heat is not necessary [49]. In addition, blood vessels, bile ducts, and nerves may be more protected, making it preferred in certain locations [46]. This could make this technology better for central tumors in the kidney where there is a risk of damage to the urinary collecting system [50].
Surveillance after ablation — CT or MRI is typically used to assess the success of tumor ablation, starting approximately one month after treatment. On CT, viable tumor is usually nodular and maintains its enhancement (>10 Hounsfield units after contrast injection), whereas successfully ablated tumor no longer enhances with contrast.
Imaging immediately following the ablation is difficult to interpret because inflammation at the periphery of the lesion may mimic viable tumor [51]. Thus, post-treatment CT imaging is usually performed at three to six months, 12 months, 18 months, and 24 months after ablation, and yearly thereafter.
OUTCOMES — Rapid advances in technique and experience make interpretation of the reported results difficult. There are no randomized trials comparing these techniques with surgery, and such trials are unlikely to be performed.
Multiple series have reported excellent short-term disease control with radiofrequency ablation (RFA), cryoablation, and microwave ablation [52]. More limited long-term outcomes in non-surgical patients are also encouraging [53-58]. The results appear comparable to those with partial nephrectomy or radical nephrectomy [9-12,48,59]. However, these results are not definitive. One meta-analysis suggested local recurrence might be slightly higher with cryoablation, while perioperative outcomes appear slightly better [60]. By contrast, another meta-analysis demonstrated no difference in recurrence [61], underscoring difficulties in comparing procedural outcomes when both procedures are effective and when no randomized comparative data exist.
Additional long-term follow-up is required before these techniques can be considered as an alternative to surgery in patients who are candidates for a definitive surgical resection. Therefore, the risk of perioperative complications and declines in renal function must be balanced against the risk of recurrence. (See "Definitive surgical management of renal cell carcinoma".)
Both RFA and cryoablation appear to be well-tolerated, with a low incidence of serious complications [27,62]. A self-limited syndrome manifested by fever and flu-like symptoms has been reported in up to one-third of patients following RFA and cryoablation [62].
Available data from retrospective series do provide some insight into the relative safety and efficacy of the percutaneous versus laparoscopic routes of treatment, as well as the relative benefits of RFA versus cryoablation.
Percutaneous versus laparoscopic ablation — There are no randomized trials that compared the efficacy of a percutaneous versus a laparoscopic approach to renal cell carcinoma (RCC) ablation.
These approaches were compared in a meta-analysis that included data from 46 observational series (28 with percutaneous treatment and 18 with laparoscopic therapy), which included 1055 patients who were treated for 1180 tumors [63]. Of the 28 series using a percutaneous approach, 21 used RFA and seven used cryoablation; of the 18 series performed with laparoscopy, three used RFA and 15 used cryoablation.
Key observations from this review included:
●Tumor size was similar in the percutaneous and laparoscopic treatment groups (2.8 and 2.5 cm, respectively).
●Major complications were less frequent with percutaneous treatment (3.1 versus 7.4 percent using laparoscopy), and the mean hospital stay was shorter (1.4 versus 3.0 days).
●A percutaneous approach was less effective than a laparoscopic approach when only the initial treatment was considered (87 versus 94), and retreatment was required more frequently. The difference in local control between the percutaneous and laparoscopic approaches was not statistically significant when retreatment was considered (92 versus 95 percent).
However, the mean length of follow-up was short for both groups (13 and 16 months for percutaneous and laparoscopic ablation, respectively). Long-term follow-up data are very limited, but limited results suggest that the recurrence-free survival rate is approximately 90 percent at five years for either approach.
A single-center comparison suggests no significant difference in renal function wither either approach [64].
RFA versus cryoablation — There are no randomized trials that compare RFA with cryoablation in the management of RCC. Numerous retrospective series have been published, which do give some insight into the outcomes with these approaches. However, any real difference between cryoablation and RFA is likely very small. The ability to conduct a randomized trial comparing these treatment approaches is limited, given the large number of patients and expense needed in order to adequately power the study and determine any meaningful difference. In addition, small differences may not affect the choice of modality, as operator expertise and comfort are likely dominant contributing factors to outcome [29].
The results with these two approaches were compared in a meta-analysis that included 47 series and consisted of patients with sporadic, localized RCCs [52]. Key observations included the following:
●The meta-analysis included 1375 patients (600 treated with RFA and 775 treated with cryoablation). The mean age of all patients treated was 67 years, the mean tumor size was 2.6 cm, and the mean duration of follow-up was 19 months. These parameters were not significantly different for patients treated with either modality.
●Cryoablation was performed laparoscopically, percutaneously, or by open surgery in 65, 23, and 12 percent of cases, respectively. By contrast, RFA was performed percutaneously or at laparoscopy in 94 and 6 percent of cases, respectively.
●Local tumor progression after a single treatment session was more frequent after RFA (12.9 versus 5.2 percent with cryoablation), and repeat ablation therapy was required more often following initial treatment with RFA (8.5 versus 1.3 percent). These differences were statistically significant.
●Overall, progression to metastatic disease was seen in 25 cases (1.8 percent). The difference in incidence of metastasis between cryoablation and RFA was not statistically significant on multivariate analysis.
●Both RFA and cryoablation (including both percutaneous and laparoscopic approaches) are effective and preserve renal function after treatment, with most studies demonstrating no significant decline in renal function [33,65].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cancer of the kidney and ureters".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Renal cell carcinoma (kidney cancer) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Surgery – Patients with stage I, II, or III renal cell carcinoma (table 1) are typically treated with surgical resection. (See "Definitive surgical management of renal cell carcinoma".)
●Ablative therapies – For carefully selected patients, radiofrequency ablation (RFA), cryoablation, microwave ablation, and other emerging therapies represent less invasive alternatives associated with less morbidity and fewer complications. However, the long-term efficacy of these approaches remains to be fully established. and patients should be counseled about the potential need for multiple treatment sessions. (See 'General principles' above.)
•Indications – Patient factors that potentially make ablation advantageous include older age, significant comorbidity, or the need to preserve as much renal parenchyma as possible (eg, patients with a solitary kidney, those with multiple lesions). (See 'Indications' above.)
•Patient selection – The most favorable lesions for use of an ablative approach are smaller RCCs (≤4 cm) and those in the periphery of the kidney. (See 'Patient selection' above.)
•Selecting therapy – There are no randomized trials comparing RFA with cryoablation, or laparoscopic approaches with percutaneous approaches. For patients who are treated with ablation, the choice of RFA, microwave, or cryoablation should be based upon the availability of local expertise. (See 'RFA versus cryoablation' above and 'Percutaneous versus laparoscopic ablation' above.)
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