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Image-guided ablation for Renal Cell Carcinoma 
  Submitted By: J. Louis Hinshaw, M.D.

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Image-guided ablation for Renal Cell Carcinoma


Authors: J. Louis Hinshaw, MD and Fred T. Lee, Jr., MD

University of Wisconsin-Madison Department of Radiology


Introduction

Renal cell carcinoma (RCC) is a very common clinical problem with over 36,000 new cases and more than 11,000 deaths in the United States in 2003 [1]. This represents a doubling in the number of RCCs diagnosed in the last 50 years, and a five-fold increase in the diagnosis of small less than 3 cm tumors over the last 20 years [1]. Identifying these tumors at a smaller size has a significant impact on patient prognosis for two reasons. One is that there are no currently available effective chemotherapies and the only hope for cure is surgical resection or physical destruction of the tumor. The smaller the tumor at diagnosis, the more likely it is that complete treatment will be possible. The other is that when these tumors are identified when they are small, they tend to be less aggressive. In the past, many of these tumors would have only been diagnosed when they were much larger because of symptoms related to mass effect from the tumor or blood in the urine. RCC is being diagnosed at a smaller size for two primary reasons: 1) they are identified incidentally on imaging performed for other reasons (i.e. motor vehicle accident, abdominal pain, etc.) and 2) improvements in CT, US, and MRI technology make it possible to identify very small tumors.

Radical nephrectomy (removal of the entire kidney along with the tumor) has long been the standard of care for the treatment of renal cell carcinoma. However, this has changed over the last several decades as surgical techniques have improved and smaller tumors have been diagnosed. Partial nephrectomy (removal of the tumor and a small margin of normal kidney) has now become the standard of care for the treatment of small RCCs in most centers, and is increasingly performed laparoscopically, limiting the associated morbidity. Clinical studies have shown that this less invasive therapy is both as effective and safer for the treatment of small, contained RCC’s, in comparison with radical nephrectomy [2, 3].

Because of the success achieved with these less traumatic techniques, other even less invasive techniques have been developed to treat small RCC. Cryoablation (the use of cold to destroy cancer cells) was initially introduced in this setting as an intra-operative technique performed while directly visualizing the tumor at surgery. Clinical experience has shown that laparoscopic cryoablation is an effective means of treating small RCC, with results essentially equivalent to partial nephrectomy [4, 5]. At that time, approximately 5-10 years ago, image-guided percutaneous (directly through the skin) ablation was being increasingly utilized in the treatment of cancer in other organ systems, particularly the liver [6-9]. As a result, there has been an increasing utilization of percutaneous and laparoscopic ablative techniques for RCC. These techniques remain under investigation and are often only available at large tertiary care medical centers, but have had extremely promising early results [10-12]. They can be used as curative procedures for smaller renal cell carcinomas, and can also be utilized in some settings as a palliative (treatment meant to improve quality of life and extend life without expectation of cure) intervention for larger tumors, as well as for the treatment of local recurrences and distant metastases in some settings. The future is very promising for ablation of renal cell carcinoma because it is proving to have comparable efficacy to surgical techniques, but has a superior safety profile, is less expensive, and can be performed in severely ill patients who would not tolerate a surgical procedure [10-16].

For a complete review of the current ablation technologies, please see our manuscript “Image guided tumor ablation, a technical overview of a less invasive cancer treatment”, also available on cancernews.com. This manuscript will specifically review the issues associated with image-guided ablation of RCC.

Are you a good candidate for image-guided ablation?

Patient selection may be the most important consideration in ensuring excellent results after image-guided tumor ablation. Ablative therapy is not an appropriate treatment for most people diagnosed with RCC. If a patient is able to tolerate resection and is an appropriate candidate, surgery is still considered the standard of care. A thorough imaging evaluation should be performed prior to initiating any therapy and should include a complete staging evaluation, including contrast-enhanced computed tomography of the chest, abdomen, and pelvis, with MRI as an alternative if there is a contraindication to CT contrast. The diagnosis of RCC is generally made based upon the imaging findings alone and biopsy (sampling of the tumor) is only performed if there are equivocal findings. Although patients with metastatic disease sometimes may have surgical resection of the kidney tumor, it is unlikely that image-guided ablation would play a significant role in the treatment of these patients. Other studies such as ultrasonography (US) of the kidney and/or inferior vena cava, as well as magnetic resonance imaging (MRI) with or without venography (evaluation of the veins) can be helpful to evaluate for the severity of disease.

The size of the tumor is the most important consideration. The likelihood of metastatic disease increases as the tumor increases in size, and in addition, ablative procedures become progressively more difficult. As the size of tumor increases, there is also an associated increase in the risk of complications related to injury to the surrounding structures. Realistically, with today’s technology and techniques, a RCC greater than five centimeters in size is less likely to be completely destroyed with image-guided ablation, although some RCC can be effectively treated even at this size [15].

The location of the tumor is also an important consideration as to whether or not the tumor can be effectively treated with ablative techniques. Tumors located around the periphery of the kidney are relatively easy to treat, while tumors located centrally are more difficult to completely treat. Treatment of central tumors is also associated with an increased likelihood of complications, particularly injury to the renal collecting system, which carries urine from the kidney to the bladder. Injury to the ureter can result in obstruction and threaten the function of the kidney. Tumors located along the anterior aspect of the kidney can also be difficult because of the risk of injuring the adjacent bowel. Although this is an uncommon complication, it can be life-threatening. Note that image-guided tumor ablation can be attempted for a tumor in any location within the kidney, but additional planning is necessary to ensure a safe outcome

Overall, with the current technology and techniques, image-guided tumor ablation is best suited to patients with peripheral tumors less than five centimeters in diameter. However, each case is unique and if a patient is severely ill and cannot tolerate surgery, has RCC in both kidneys, has poor renal function, or has a syndrome (such as Von Hippel Lindau) that makes them susceptible to developing multiple RCCs in their lifetime, then image-guided tumor ablation may be a consideration for people who fall outside of these guidelines.

Technology

Cryoablation and radiofrequency ablation are the primary modalities utilized for RCC ablation. There are other alternative modalities that are under development, including high intensity focused ultrasound (HIFU) and microwave, which have potential advantages that may be realized in the future. However, these technologies are not widely utilized at this time.
Cryoablation

Cryoablation is antithesis of the other thermal ablation techniques, utilizing freezing rather than heat to cause tissue destruction. When tissues are frozen, crystals form within them and the cells expand, both of which damage the cell. When the cells are subsequently thawed, this results in cellular disruption and death. Temperatures as low as -160 degree C can be achieved with this technique and any tissue cooled to less than approximately -20 degree C is irreparably damaged.

Early in its development, cryoablation could not be performed percutaneously (through the skin) because the probes that it used were too large to use safely. Therefore, it was performed at the time of surgery, when the tumor could be directly visualized. However, recently, there have been technical advances in the equipment that have resulted in much smaller probes and cryoablation can now be utilized percutaneously. Limited clinical studies have been performed to date and the only large trial reported had almost 100% complete treatment of tumors even up to 7.2 cm in diameter [11]. The advantages of performing the procedure percutaneously, if possible, is that it is associated with a shorter recovery time, shorter hospital stay, less complications, and a significantly lower cost [17].

There are several potential advantages of cryoablation over the heat-based ablation modalities. The main advantage is that the iceball formed during the ablation is highly visible with CT, US, and MRI. This allows very precise control of the ablation and limits injury to adjacent structures (Figure 1). The area of ablation is not nearly so well-defined or controlled with the heat-based ablation modalities. Also, much larger ablations can be performed with cryoablation (up to approximately 12 cm) as compared with the currently available heat-based ablations (maximum of approximately 7 cm).

Figure 1: US-guided cryoablation of renal cell carcinoma of the left kidney in a woman with Von-Hippel Lindau Disease (VHL). VHL puts the patient at risk for having multiple renal cell carcinomas during their life.



Figure 1: a) Contrast-enhanced MRI image through the abdomen prior to cryoablation. The renal cell carcinoma is identified as an avidly enhancing rounded mass along the posterior left kidney (arrow).



Figure 1: b) Grey-scale US image prior to the ablation. The renal cell carcinoma is identified as a rounded mass extending off the posterior kidney (arrows). Note the dark area next to the mass, which represents a renal cyst. Contrast-enhanced CT image through the abdomen after the cryoablation.



Figure 1: c) Grey-scale US image during the ablation. The renal cell carcinoma is now obscured by the iceball that has formed around the cancer (arrow).



Figure 1: d) Contrast-enhanced MRI image through the abdomen after the cryoablation. The mass is no longer enhancing, showing that it has been devascularized and is no longer viable (arrow).


The primary disadvantage of cryoablation is the perceived increase risk of bleeding associated with the procedure as compared with the heat-based ablation modalities, which cauterize the tract. However, the only controlled study performed to date did not identify any increase in hemorrhage after cryoablation of the liver as compared with RF ablation and microwave ablation [18].

Radiofrequency

Radiofrequency ablation (RFA) is currently the most frequently utilized percutaneous ablation modality. It has been more extensively studied and more widely utilized clinically. During RFA, high-frequency alternating electrical current (~500 kHz) is passed through a needle (electrode) that is positioned within the tumor. The electrical current results oscillation of the ions directly adjacent to the electrode and this results in frictional heating of these tissues. The heat is subsequently propagated through the tissues. Any tissue heated to more than 50-60 degree C dies immediately and any tissue heated to above approximately 40 degree C will die if the temperature is maintained for an adequate period of time. The time necessary to result in cell death depends on the temperature. The technologies have been rapidly improving over the last several decades and relatively large and robust ablations are now possible.

There are technical issues related to the deposition of RF into the tissues that limits the volume of tissue that can be destroyed at one time. As a result, the size of tumor that can be effectively treated by RF may be slightly smaller than what is possible with cryoablation. However, clinically, the results have been similar with excellent clinical success in treating tumors less than 3 cm in diameter, moderate success with tumors in the 3-5 cm range and less success in tumors greater than 5 cm in diameter (Figure 2).

Figure 2: US-guided percutaneous RF ablation of renal cell carcinoma of the right kidney.



Figure 2: a)Contrast enhanced MRI image through the abdomen prior to RF ablation. The renal cell carcinoma is identified as an avidly enhancing mass extending off the posterior aspect of the right kidney (arrow).



Figure 2: b)Grey-scale US image prior to the ablation. The renal cell carcinoma is identified as a rounded mass extending off the posterior kidney (arrows).



Figure 2: c) Grey-scale US image during RF ablation. The renal cell carcinoma is now obscured by the gas bubbles that form as the tissue water boils during the RF ablation (arrows).



Figure 1: d) Contrast enhanced MRI image through the abdomen after RF ablation and resection. The renal cell carcinoma is now devascularized and non-enhancing (arrow).


The primary disadvantages of RF ablation are that it is relatively painful, both during and after the ablation, which means that general anesthesia may be necessary for the procedure and narcotic pain relievers may be required for some period of time after the procedure (usually less than 24 hours, at which time the pain decreases significantly). It is also thought to be more likely to injure the renal collecting system than cryoablation, although this is anecdotal and not based upon any direct scientific evidence.

Microwave

Microwave (MW) ablation is promising. However, there is only one system available for clinical use in the United States at this time and this system is not capable of creating large ablations. Microwave ablation (MW) is similar to RF, but has several theoretical advantages that may offer better and more consistent ablation of malignancies once the technology has improved. MW ablation makes use of the same energy as a standard microwave oven, but deposits that energy directly into the tissues around the probe. Since it heats a volume of tissue around the applicator, it is more efficient than radiofrequency ablation and the tissues can be heated to higher temperatures. Very little clinical work has been done in the kidney with MW to date, but it may prove to be more effective at creating large and confluent ablations than RF when the technology improves.
High-intensity Focused Ultrasound

High-intensity Focused Ultrasound (HIFU) is in theory the optimal technology for performing ablation because it is completely non-invasive. HIFU uses highly focused ultrasound energy to vibrate tissue, causing frictional heating. Significant heating of the tissue can occur if the focused US energy is directed at the target tissue for an adequate period of time. However, it can be difficult to accomplish this in a clinical setting because the target tissue moves with patient breathing, or movement. As a result, achieving consistent ablative temperatures has proven to be quite difficult. Thus far, the primary use for HIFU has been in the treatment of uterine fibroids, a benign tumor of the uterus. HIFU has been effective at treating the symptoms associated with fibroids, but often does not achieve complete destruction of the tumor, as you would need for the treatment of a cancer. Some of these limitations are being addressed with advanced computer targeting systems, and these advances may eventually overcome these problems.

What can you expect for the procedure?

Image-guided tumor ablation is a procedure that has been independently developed and advanced at many different institutions. As a result, there is some variation in how the procedure is performed. This includes which ablation modality is utilized, whether or not the patient will be under general anesthesia, or have conscious sedation, and what imaging modality is used for guidance and monitoring of the ablation. However, there has been excellent knowledge sharing between the institutions to ensure that critical factors are more uniform.

At our institution, we perform the procedure with the patient on the CT scanner. However, we utilize US for guidance and monitoring the ablation the majority of the time. Then we have completed the treatment, we obtain a contrast-enhanced CT. This allows us to identify any untreated tumor at that time and complete the therapy as needed. Some medical centers will perform this initial evaluation at a later time (1-4 weeks after the ablation) and repeat the treatment at that time if necessary.

The ablation is usually performed as an outpatient procedure, although you may spend one night in the hospital for observation after the ablation. If RF was used for your ablation, then you are likely to have significant discomfort for the first 24 hours, after which it will quickly decrease. With cryoablation, there is usually very minimal pain after the procedure. In fact, significant pain afterwards, or pain that increases over time, can indicate that there is post-ablation bleeding, which can be painful and even life-threatening if the blood loss is large enough. Most patients can return to their normal activities within a week.

Not all ablations can be completed using a percutaneous approach. As a result, laparoscopic assistance or open ablation may be necessary. At our institution, the radiologist performs the procedure in cooperation with a urologist.

Possible Complications

Renal cryoablation and RF ablation have both proven to be extremely safe. Less than 10% of patients encounter a significant complication and most of these complications are relatively minor and self-limited. On the other hand, surgery, even relatively non-invasive surgery like nephron-sparing surgery (partial nephrectomy), has a major complication rate of approximately 14% with almost 1% mortality according to a very review article published in 2001 [2].

Hemorrhage

Bleeding is the most frequently reported complication. However, the bleeding is usually small volume and limited by the small, contained space surrounding the kidney. If large volume, bleeding can result in the need for blood transfusions and hospitalization.

Collecting system injury

Injury to the renal collecting system that carries urine from the kidney to the bladder is the most feared complication as it can threaten the function of the entire kidney (Figure 3).

Figure 3: Ureteral stricture following intra-operative RF ablation of renal cell carcinoma of the right kidney.



Figure 3: a) Contrast-enhanced MRI through the abdomen after RF ablation. The renal cell carcinoma has been fully treated as is identified as a non-enhancing region along the anterior right kidney (arrows).



Figure 3: b)T2-weighted MRI through the abdomen after RF ablation. Unfortunately, the patient has developed a ureteral stricture related to the RF ablation despite attempts in the operating room to protect the ureters, which has resulted in obstruction and hydronephrosis (distention of the collecting system) of the right kidney (arrow). This complication required ureteral stent placement.


Fortunately, it is a relatively infrequent complication and, if anticipated, can often be avoided. It is most frequently seen after treatment of central tumors, or tumors along the lower border of the kidney. In these situations, precautions can be undertaken to make this complication less likely, but sometimes it is not safe to perform ablations in these locations.

Damage to adjacent structures

A bothersome, but usually time-limited complication, is injury to the nerves that innervate the skin of the side and abdomen. This can result in a neuropathy (injury to the nerve with associated abnormal sensations along the course of the nerve). If this occurs, the patient will have painful sensations and hypersensitivity that develop immediately after the ablation. The majority of the time, this resolves over the course of 1-2 months and no cases have been reported where the symptoms are permanent. In the meantime, both topical and oral medications can be given to limit the symptoms.

The other complication that can arise is injury to the bowel, which may be located adjacent to the tumor. This can be a devastating complication with subsequent infection and even death. As a result, tumors that are located closely adjacent to bowel are often treated with surgical assistance at our institution. Alternatively, there are some techniques that can be used to protect the bowel during the ablation if a percuteneous approach is used.

Follow-up after the ablation

Although there is some variability as to the follow up that is required after ablation of a renal tumor, there are some relatively consistent practices as well. Either a contrast enhanced CT or MRI should be performed either immediately after, or soon after the ablation, to ensure that the tumor has been completely treated. If this shows that the tumor has been completely destroyed, then a contrast-enhanced CT or MRI should be performed 3, 6, 9, 12, 18, and 24 months after the ablation. If there is evidence to suggest that the tumor has come back on any of these studies, then it should be treated again. If there is no evidence that the tumor has re-grown, then the follow-up imaging can be performed less frequently after two years, often annually.

Conclusion

Image-guided tumor ablation is a relatively new technology. However, it has proven to be extremely promising in early clinical work treating small renal cell carcinomas. It is a very safe technique and short-term results are comparable to those obtained with surgery in patients who have disease that is appropriate for this treatment. At this time, it is most appropriate to recommend this treatment to patients who have small (<5 cm) tumors along the periphery of the kidney and who either can not, or do not want to have surgical removal. 


 


Additional Authors:  

Works Cited:  
  1. SEER, United States Surveillance, Epidemiology and End Results Program. 2003.
2. Uzzo, R.G. and A.C. Novick, Nephron sparing surgery for renal tumors: indications, techniques and outcomes. J Urol, 2001. 166(1): p. 6-18.
3. Fergany, A.F., K.S. Hafez, and A.C. Novick, Long-term results of nephron sparing surgery for localized renal cell carcinoma: 10-year followup. J Urol, 2000. 163(2): p. 442-5.
4. Gill, I.S., et al., Renal cryoablation: outcome at 3 years. J Urol, 2005. 173(6): p. 1903-7.
5. Gill, I.S., et al., Laparoscopic renal cryoablation in 32 patients. Urology, 2000. 56(5): p. 748-53.
6. Jungraithmayr, W., et al., Cryoablation of malignant liver tumors: results of a single center study. Hepatobiliary Pancreat Dis Int, 2005. 4(4): p. 554-60.
7. Weber, S.M. and F.T. Lee, Jr., Expanded treatment of hepatic tumors with radiofrequency ablation and cryoablation. Oncology (Williston Park), 2005. 19(11 Suppl 4): p. 27-32.
8. Seifert, J.K., et al., Cryotherapy for liver metastases. Int J Colorectal Dis, 2000. 15(3): p. 161-6.
9. Iannitti, D.A., et al., Laparoscopic cryoablation of hepatic metastases. Arch Surg, 1998. 133(9): p. 1011-5.
10. Mogami, T., et al., Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell carcinoma. Int J Clin Oncol, 2007. 12(2): p. 79-84.
11. Atwell, T.D., et al., Percutaneous cryoablation of 40 solid renal tumors with US guidance and CT monitoring: initial experience. Radiology, 2007. 243(1): p. 276-83.
12. Silverman, S.G., et al., Renal tumors: MR imaging-guided percutaneous cryotherapy--initial experience in 23 patients. Radiology, 2005. 236(2): p. 716-24.
13. Gervais, D.A., R.S. Arellano, and P.R. Mueller, Percutaneous radiofrequency ablation of renal cell carcinoma. Eur Radiol, 2005. 15(5): p. 960-7.
14. Gervais, D.A., R.S. Arellano, and P. Mueller, Percutaneous ablation of kidney tumors in nonsurgical candidates. Oncology (Williston Park), 2005. 19(11 Suppl 4): p. 6-11.
15. Gervais, D.A., et al., Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiology, 2003. 226(2): p. 417-24.
16. Gervais, D.A., et al., Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology, 2000. 217(3): p. 665-72.
17. Shadid A, H.J., Nakada SY, Hedican S, Moon T, Lee FT Jr., Comparison of cost effectiveness and outcome of percutaneous and laparoscopic renal cryoablation. Abdominal Radiology Course, Society of Gastrointestinal Radiology, 2007. Scientific presentation.
18. Shock, S.A., et al., Hepatic hemorrhage caused by percutaneous tumor ablation: radiofrequency ablation versus cryoablation in a porcine model. Radiology, 2005. 236(1): p. 125-31.

* McGahan JP, Brock JN, Tessluk H, Gu WZ, Schneider P, Browning PD. Hepatic ablation with the use of radio-frequency electrocautery in the animal model. J Vasc Interv Radiol 1992;3:291-7
 
 


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