Kidney tumor ablation treats nonsurgical candidates

Over 35,000 new cases of renal cell carcinoma occurred in the U.S. in 2001,¹ most of them detected as incidental imaging findings on CT, MR, or ultrasound.^2,3 Since most of these tumors are relatively small when detected, the classic clinical triad of flank pain, hematuria, and palpable mass is now rarely encountered. Many of these incidentally discovered RCCs are also slow growing. Bosniak et al showed that RCCs smaller than or equal to 3.5 cm grow at an average rate of 0 to 1.1 cm/year (mean 0.36 cm/year).⁴

Most RCCs are surgically removed, and resection of RCC remains the standard of care.⁵ Traditional treatment has been open complete nephrectomy, but the search for less invasive procedures as well as for nephron-sparing surgery has led to alternative surgical approaches.^6,7 These include partial open and complete or partial laparoscopic nephrectomy. For appropriately selected tumors, nephron-sparing resection has shown outcomes equivalent to total nephrectomy.^5-7

Open, partial, and laparoscopic nephrectomies are now available to most patients. For some patients, however, an even less invasive procedure may be indicated. Patients with solitary kidneys or limited renal function, for example, may not tolerate even a partial nephrectomy without requiring postoperative dialysis. For patients with bilateral or multiple RCCs, further partial nephrectomy may tip them to dialysis. Finally, patients with extensive comorbid conditions may face unacceptable risks from surgery and general anesthesia.

Percutaneous ablation may provide an alternative treatment option for all these groups of patients. Ablation of RCC left in situ has been performed intraoperatively using cryoablation before percutaneous cryoprobes became available.⁸ Cryoablation induces tumor necrosis by freezing tissue. The first needle applicators suitable for percutaneous application were radiofrequency electrodes. Thus, most of the published literature on percutaneous ablation of renal masses is on RF ablation, which induces tumor necrosis via lethal hyperthermia. Now that percutaneous cryoprobes are available, experience with image-guided percutaneous cryoablation will undoubtedly increase. A microwave ablation system with percutaneous applicators, also based on hyperthermia, has become available in the U.S., but no published reports of its use in renal tumors left in situ have yet appeared.

In 1997, Zlotta et al reported the first percutaneous application of renal RFA, confirming its safety and feasibility under local analgesia.⁹ In his initial series, three tumors were subsequently resected, confirming RFA's ability to create extensive local necrosis in in vivo renal tumors.⁹ In 1999, McGovern et al reported the first in situ renal tumor treated solely with RFA.¹⁰ In 2000, Gervais et al presented the first series of such patients treated solely with RFA.¹¹ Nine tumors in eight patients underwent RFA with postablation imaging surveillance to monitor treatment response. Because the tumors were left in situ, assessment of tumor response was performed with imaging. Gervais et al applied a CT or MR interpretive scheme based on extrapolation of radiologic-pathologic correlation work in liver tumor ablations performed by Goldberg et al.^11,12 In this study, necrosis was shown to correlate with lack of enhancement to within 2 mm and tumor enhancement was shown to correlate with viable tumor.¹² This interpretative scheme has since been widely applied by other investigators.

Since these early reports, multiple series of renal tumors treated with percutaneous ablation in vivo and left in situ have been published.^13-26 The accompanying table summarizes the results of the larger published series of percutaneous RFA of renal tumors. These series reveal that for small renal tumors, RFA results in complete necrosis at imaging in 79% to 100% of cases.^13-26 Differences in results are related partly to differences in protocol. In one protocol in which early residual disease was treated with repeat percutaneous ablation, for example, 100% complete necrosis at imaging was achieved for all tumors 4 cm or smaller.¹³ The series with the lowest success rate (79%) used less powerful generators than are now commonly available, perhaps resulting in less complete ablation.¹⁹ Modern systems average over 90% complete necrosis in small tumors. The follow-up period following renal tumor ablation has been short, however, averaging less than three years.

CASE EVALUATION

Case selection for percutaneous ablation involves consideration of three broad issues: patient factors, tumor factors, and feasibility factors.

- Patient factors. Factors that define the clinical indications for percutaneous ablation of RCC include comorbid conditions rendering surgery risky, limited renal function, and multiple RCC or its predisposition as with von Hippel-Lindau disease or familial types of RCC.¹³ Patient evaluation is best done in consultation with a urologist experienced in treatment of RCC to ensure that all surgical options have been considered.

- Tumor factors. Tumor size and location must be considered. Small tumors are ideal because of the technical limitations of the ablation systems with respect to the volume of tissue that undergoes necrosis. The size criterion for inclusion of a "small" tumor in RFA has ranged from 2.5 to 4 cm, depending on the series.^13-26 A recent ROC analysis based on 100 cases suggests that 4 cm is an appropriate definition, with all tumors 4 cm or smaller undergoing complete necrosis, 92% (48/52) in one ablation session and the remaining 8% in two sessions. Larger tumors have been completely ablated in some series, but experience with these is less extensive, and increasing size often requires an increasing number of ablation sessions.¹³

Tumor location also affects ablation results. The ideal renal tumor for percutaneous ablation is an exophytic RCC. The surrounding perirenal fat serves as an insulator to allow higher temperatures of longer duration to be achieved with RFA. Central tumors, on the other hand, can prove more difficult to ablate because of proximity to large hilar vessels. Blood flow provides constant cooling during RFA, thus limiting the effect of the ablation.

- Feasibility. Case evaluation assesses whether the case is feasible and safe using a percutaneous approach. A safe percutaneous path to the tumor, avoiding bowel and large vessels, must exist. Even if a percutaneous approach is possible with the needle applicator, the proximity of the tumor to other structures that might be damaged by thermal injury must be considered. For renal tumors, this means careful attention to the location of bowel, ureter, and ureteropelvic junction. Even when these structures are adjacent to tumor or within a few millimeters, percutaneous ablation may still be possible if the structures can be separated from tumor via positional maneuvers, hydrodissection, instillation of CO2, balloon displacement, or manual compression.^14,27,28 For tumors that cannot be separated from vital structures, surgical approaches to ablation or resection or imaging follow-up remain options.

PERFORMING ABLATION

Planning and performing a renal tumor ablation requires diligent attention to the findings on pre-ablation diagnostic imaging. Tumor margins must be known to plan the desired size of the ablation zone. Pavlovich et al emphasized preservation of normal renal parenchyma in their early series.¹⁹ This technique may in part have been responsible for their lower rate of complete ablation.

Although achievement of a 5 to 10-mm margin of normal renal tissue at the RCC/kidney interface is not mandatory, Ogan et al have advocated striving for a small margin of renal tissue when performing ablation to help ensure more complete tumor necrosis.²³ An approach that includes margins in the planned ablation zone is further supported by the work of Goldberg et al, who found that viable tumor cells remained present at the margins in four of five liver tumors where the zone of ablation was equal in size to the tumor in the absence of enhancement at CT.¹² These spatial resolution limitations of imaging technology must be considered when planning and performing percutaneous ablation.

A single applicator may not result in an ablation zone of adequate size, or the geometry of the ablation zone may not correspond to the tumor geometry, leaving viable tumor. For this reason, multiple applications are necessary. Cryoablation uses multiple single cryoprobes, placed and activated simultaneously, until multiple freeze-thaw cycles are completed. On the other hand, most RF electrode systems are applied as a single applicator with multiple overlapping ablations performed in one session by repositioning of the electrode after each ablation to cover the entire tumor volume (Figure 1). New technology allows up to three simultaneous electrode placements, with the generator delivering power to each electrode sequentially.²⁹

CT, MR, or ultrasound can provide imaging guidance for positioning of the needle applicators.^13,25,30 MR can provide accurate assessment of the treatment margin in multiple planes while the patient is still on the table, but it is expensive, not widely available for interventional use, and requires special monitoring equipment as well as special MR-compatible applicators. Ultrasound can provide rapid real-time evaluation of needle position without the use of ionizing radiation, but it may not easily demonstrate some tumors, particularly on the left. Echoes generated by RFA and the echogenic proximal edge of the iceball at cryoablation preclude accurate monitoring of the treatment effect and limit visibility for subsequent repositioning of RF applicators for overlapping ablations. CT provides accurate localization of the needle applicators, and visibility of the applicators is not limited by treatment effects such as gas formation or small amounts of hemorrhage. Neither ultrasound nor noncontrast CT predicts the precise location of the treatment margin. Near the end of an ablation, a bolus of contrast material may be useful in demonstrating remaining tumor. Contrast material may concentrate near the ablation zone, however, limiting the utility of subsequent boluses of contrast material.

RF systems allow for electrocautery of the needle tract upon removal. Tract ablation theoretically limits tract seeding and the risk of hemorrhage.

PATIENT MANAGEMENT

Issues to consider in preparing a patient for ablation include tissue diagnosis, status of outpatient versus short-stay inpatient care, and choice of sedation versus anesthesia. Percutaneous ablation of RCC can be performed as an outpatient procedure,¹³ but admission may be required to allow complete recovery from sedation. Intravenous sedation is used in many cases (midazolam 2 to 5 mg, fentanyl 100 to 300 micrograms, meperidine 50 to 100 mg).¹³ Selected patients may require general anesthesia if they do not meet institutional criteria for IV sedation.

Differential diagnosis of a solid enhancing mass on CT or MRI includes RCC, fat-poor angiomyolipoma, oncocytoma, metastases, or lymphoma. Definitive pathologic diagnosis of a renal mass left in situ requires needle biopsy. Traditionally, for management purposes, urologists have treated a solid enhancing renal mass at CT or MR as renal cell carcinoma. Since needle biopsies may miss RCC in a small number of cases, all these masses were resected, providing material for histology. Leaving the renal tumor in situ after ablation, however, provides no tissue diagnosis to help guide postablation management.

A recent report found that 10 of 27 patients referred for ablation had benign masses.³¹ Thus, most patients undergo needle biopsy to establish a diagnosis prior to ablation. In selected cohorts, such as patients with von Hippel-Lindau, some have argued against biopsy prior to ablation because the likelihood of RCC is high regardless of biopsy results.¹⁹ This area remains controversial.

Following ablation, imaging follow-up with unenhanced and enhanced CT or MR allows for response assessment (Figures 1E and 1F).¹¹ Although imaging intervals vary among institutions, most radiologists perform imaging within one month for prompt detection of residual viable tumor.^13-26,30 Small foci of residual viable tumor can then be ablated again.¹⁴ Because of the lack of long-term data on the efficacy of ablation, imaging continues indefinitely, initially at three to six-month intervals and then at annual intervals once no viable tumor has been confirmed in the first year or two of follow-up.

Complications are rare following RFA compared with partial nephrectomy.^5-7,13 The most common is hemorrhage, and this may be more common in central tumors.¹³ Urinary collecting system obstruction can occur from ureteral injury with stricture formation or from bleeding into the collecting system.^13,14 Injury to nerves from the lumbar plexus may cause transient paresthesias along cutaneous nerve distributions.^13,15,19 Tract seeding has been reported in a single case in which a cutaneous tumor was subsequently removed.¹⁷ There is also potential for bowel injury or pleural complication requiring thoracostomy drainage.

Dr. Gervais is director of abdominal interventional radiology and an assistant professor of radiology, Dr. Arellano is director of abdominal intervention clinic operations and an instructor of radiology, and Dr. Mueller is director of abdominal imaging and intervention and a professor of radiology, all at Massachusetts General Hospital and Harvard Medical School.

References

1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001;51:15-36.

2. Smith SJ, Bosniak MA, Megibow AJ, et al. Renal cell carcinoma: earlier discovery and increased detection. Radiology 1989; 170:699-703.

3. Jayson M, Sanders H. Increased incidence of serendipitously discovered renal cell carcinoma. Urology 1998;51:203-205.

4. Bosniak MA, Birnbaum BA, Krinsky GA, Waisman J. Small renal parenchymal neoplasms: further observations on growth. Radiology 1995; 97:589-597.

5. Novick AC, Campbell SC. Renal Tumors. In: Walsh PC, ed. Campbell's Urology, 8th ed. Philadelphia: Saunders, 2002;2672-2731.

6. Uzzo RG, Novick AC. Nephron sparing surgery for renal tumors: Indications, techniques and outcomes. J Urol 2001;166:6-18.

7. Reddan DN, Raj GV, Polascik TJ. Management of small renal tumors: an overview. Am J Med 2001;110:58-562.

8. Gill IS, Remer EM, Hasan WA, et al. Renal cryoablation: outcome at 3 years. J Urol 2005;173:1903-1907.

9. Zlotta AR, Wildshutz 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.

10. McGovern FJ, Wood BJ, Goldberg SN, Mueller PR. Radiofrequency ablation of renal cell carcinoma via image guided needle electrodes. J Urol 1999;161:599-600.

11. Gervais DA, McGovern FJ, Wood BJ, et al. Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology 2000;217:665-672.

12. Goldberg SN, Gazelle GS, Compton CC, et al. Treatment of intrahepatic malignancy with radiofrequency ablation: radiologic-pathologic correlation. Cancer 2000;88:2452-2463.

13. Gervais DA, McGovern FJ, Arellano RS, et al. Radiofrequency ablation of renal cell carcinoma part 1: indications, results, and role in patient management over a six year period and ablation of 100 tumors. AJR 2005;64-71.

14. Gervais DA, Arellano RS, McGovern FJ, et al. Radiofrequency ablation of renal cell carcinoma part 2: lessons learned with ablation of 100 tumors. AJR 2005;72-80.

15. Farrell MA, Charboneau WJ, DiMarco DS. Imaging-guided radiofrequency ablation of solid renal tumors. AJR 2003;180:1509-1513.

16. Su LM, Jarrett TW, Chan DY, et al. Percutaneous computed tomography-guided radiofrequency ablation of renal masses in high surgical risk patients: preliminary results. Urology 2003;61(4 Suppl 1):26-33.

17. Mayo-Smith WW, Dupuy DE, Parikh PM, et al. Imaging-guided percutaneous radiofrequency ablation of solid renal masses: technique and outcomes of 38 treatment sessions in 32 consecutive patients. AJR 2003;180:1503-1508.

18. Ahrar K, Matin S, Wood CG, et al. Percutaneous radiofrequency ablation of renal tumors: technique, complications, and outcomes. J Vasc Interv Radiol 2005;16:679-688.

19. Pavlovich CP, Walther MM, Choyke PL, et al. Percutaneous radio frequency ablation of small renal tumors: initial results. J Urol 2002;167:10-15.

20. Zagoria RJ, Hawkins AD, Clark PE, et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR 2004;183:201-207.

21. Veltri A, De Fazio G, Malfitana B, et al. Percutaneous US-guided RF thermal ablation for malignant renal tumors: preliminary results in 13 patients. Eur Radiol 2004;14:2303-2310.

22. Mahnken AH, Rohde D, Brkovic D, et al. Percutaneous radiofrequency ablation of renal carcinoma: preliminary results. Acta Radiol 2005;46:208-214.

23. Ogan K, Jacomides L, Dolmatch BL, et al. Percutaneous radiofrequency ablation of renal tumors: technique, limitations, and morbidity. Urology 2002;60:954-958.

24. Roy-Choudhury SH, Cast JEI, Cooksey G, et al. Early experience with percutaneous radiofrequency ablation of small solid renal masses. AJR 2003;180:1055-1061.

25. Lewin JS, Nour SG, Connell CF, et al. Phase II clinical trial of interactive MR imaging-guided interstitial radiofrequency thermal ablation of primary kidney tumors: initial experience. Radiology 2004;232:835-845.

26. de Baere T, Kuoch V, Smayra T, et al. Radiofrequency ablation of renal cell carcinoma: preliminary clinical experience. J Urol 2002;167:1961-4.

27. Kam AW, Littrup, Walther MM, et al. Thermal protection during percutaneous thermal ablation of renal cell carcinoma. J Vasc Interv Radiol 2004;15:753-758.

28. Farrell MA, Charboneau JW, Callstrom MR, et al. Paranephric water instillation: a technique to prevent bowel injury during percutaneous renal radiofrequency ablation. AJR 2003;181:1315-1317.

29. Haemmerich D, Lee FT Jr. Schutt DJ, et al. Large-volume radiofrequency ablation of ex vivo bovine liver with multiple cooled cluster electrodes. Radiology 2005;234:563-568.

30. Shingleton WB, Sewell PE. Cryoablation of renal tumors in patients with solitary kidneys. BJU Int 2003;92:237-239.

31. Tuncali K, vanSonnenberg E, Shankar S, et al. Evaluation of patients referred for percutaneous ablation of renal tumors: importance of a preprocedural diagnosis. AJR 2004;183:575-582.