Radiofrequency Ablation of Metastases from Renal Cell Carcinoma: Technique, Complications, and Midterm Outcome

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1 european urology supplements 6 (2007) available at journal homepage: Radiofrequency Ablation of Metastases from Renal Cell Carcinoma: Technique, Complications, and Midterm Outcome Christian Kloeters a, *, Ann-Kathrin Mager a, Manfred Johannsen b, Martin Ringsdorf b, Andreas Roemer b, Maximilian Tuellmann b, Bernd Hamm a, Eike Hein a, Patrik Rogalla a a Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany b Department of Urology, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany Article info Keywords: Image guidance Metastases Radiofrequency ablation Renal cancer Abstract Objectives: To determine the therapeutic effect of radiofrequency ablation of metastases from renal cell carcinoma (RCC) with respect to complications and local tumor control. Methods: Sixty-six radiofrequency ablations under computed tomography (CT) fluoroscopy control were performed in 38 patients with metastatic RCC. The ablation was performed for local tumor volume reduction in 7 patients and for complete local tumor control in 31 patients. Sites of ablation included the liver (39), lung (11), kidney (11), adrenal glands (2), and lymph nodes or soft tissue (3). CT scanning was performed immediately after the ablation procedure and at 3, 6, 12,18, and 24 mo during the follow-up period. Size of the target lesion, ablation duration and temperature, and complications associated with the ablation procedure and rate of local recurrence were recorded. Results: At a mean follow-up of 10 mo (median: 12 mo; range: 3 47 mo), no complications were observed except two pneumothoraces that did not require further intervention. The average metastasis size was 7.9 cm in patients treated for volume reduction and 2.3 cm in patients treated for local tumor control. One local recurrence in the kidney, caused by incorrect needle placement during the ablation procedure, was detected on the first imaging control. The average ablation duration per metastasis was 11.5 min; a mean temperature of C was reached in the target lesion. Conclusions: Percutaneous radiofrequency ablation represents a safe treatment technique for metastases from RCC. Indications in selected patients may be both tumor volume reduction and complete ablation of the metastatic site. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Radiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany. Tel ; Fax: address: c.kloeters@gmx.de (C. Kloeters) /$ see front matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eursup

2 654 european urology supplements 6 (2007) Introduction Percutaneous radiofrequency ablation (RFA) has become a viable option for minimally invasive treatment of many sites of malignant diseases, in particular for focal liver lesions [1]. Several recent reports indicate that RFA may also be applied for treatment of primary renal cell carcinoma (RCC) [2,3]. Single-center and multicenter studies have shown a relatively low incidence of incomplete treatment and local recurrence. In addition, the number and interval for posttherapy imaging control has been debated, and the lack of general guidelines has been noted in a consensus statement from the Working Group on Image-Guided Tumor Ablation [4]. Relatively little data exist on the treatment results of metastases from RCC, complication rates, and midterm outcome. The purpose of our study was to analyze retrospectively the ablation treatment results and complication rates in patients with one or more metachronous metastases of a surgically resected primary RCC. 2. Materials and methods From September 1999 to February 2007, a total of 245 RFA procedures were performed in our institution. Of these patients, 38 patients were referred for ablation of metastases originating from primary RCC. Reasons for referral for ablation instead of surgical resection were the presence of more than one metastasis in 7 patients, medical contraindications for surgery in 31 patients, including severe coronary artery disease, multiple renal artery stents, and patient s refusal of surgery. The mean age of the patients was 61.8 yr (median: 63 yr). Sixty-six metastases were ablated in these patients, all of whom were referred by the Department of Urology; histologic proof either existed or was obtained prior to the ablation procedure. Cross-sectional imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) was available for treatment planning. The ablation was performed with the intention of local tumor volume reduction in 7 patients with a total of 16 metastases (2 patients with one lesion, 4 with two lesions, and 2 patients with three lesions) due to a tumor size >5 cm in its largest diameter measured on CT images. Thirty-one patients with a total of 50 metastases were treated with the intention of complete ablation of the target metastasis. The tumor was located in the liver in 25 patients, in the lung in 10, in the remaining kidney in 11, in adrenal glands in 2, and in lymph nodes or soft tissues in 2 patients. The size of the tumors ranged from 10 to 50 mm with a mean size of 23 mm. In 27 patients a solitary tumor was ablated; 3 patients had two lesions and one had three lesions within the same organ in one session. Additionally, 12 patients were treated twice and one patient was treated three times. The primary renal cancer was surgically resected in all patients. Seven patients received systemic therapy within 3 mo before and after the ablation procedure. All these patients had mixed responses to immunotherapy with a progressive lesion in the liver and stable or responding metastases elsewhere. To comply with generally accepted oncologic treatment guidelines, all planned ablation procedures were discussed in depth during an interdisciplinary conference. All patients included in our study had signed an informed consent. Patients were also informed as to the alternative character of the treatment procedure that does not represent a widely applied method for cancer treatment with curative or palliative intent. Prior to inclusion in the study, two prerequisites had to be fulfilled: patients needed to be able to receive iodized contrast agents in case bleeding complications would require further CT scanning, and laboratory values for partial thromboplastin time and prothrombin time had to be within normal limits. The patients were advised that mild fevers may occur over a period of 2 d after tumor ablation. Analgosedation was performed during the ablation procedure with intravenous administration of 15 mg piritramide (Dipidolor 1, Janssen-Cilag, Germany) and 5 mg midazolam (Dormicum 1, Roche, Switzerland). The patient was positioned as comfortable as possible because the entire procedure could last up to 1 h, depending on the number of treatment locations and the size of the target tumor. After precise localization of the ablation target and definition of the access route, the entry point was marked on the skin. After the skin was sterilized and sterile drapes were applied, topical anesthesia (prilocaine, Xylonest 1, AstraZeneca) was injected subcutaneously. The needle position was documented on a single CT scan to confirm the access route and detect possible changes in the organs due to patient motion. A radiofrequency cool-tip needle (Radionics, Burlington, VT, USA) was then introduced under CT fluoroscopy control [5] and advanced into the center target; in case the target was >5 cm, a cluster-needle (three needles bundled) was used, and for smaller tumors, single needles were used. After repeat confirmation of the correct needle position, the radiofrequency ablation procedure using the Radionics CC1 200-W generator was initiated during continuous water cooling of the needle tip. All procedures were done with automatic impedance control setting to avoid tissue carbonization. Two possible points of interruption of the procedure existed: after the fifth automatic energy interruption by the device or after a total of 13 min. After termination of the energy deposit, the water cooling was stopped and the needle tip measured the temperature reached in the center of the metastasis. Finally, while keeping a temperature of about 80 8C in the needle tip by means of applying 20 W of energy, the needle was slowly retracted. This procedure was done for coagulation of blood in the needle tract. Following the ablation procedure, immediate CT scanning was performed after intravenous administration of 120 ml iodized contrast material (Xenetix 1 350, Guebert) for detection of potential bleeding complications. Patients were admitted for 2 d after the procedure; further CT scanning was performed after 3, 6, 12, 18, and 24 mo in accordance with our institutional follow-up guidelines. The size of the ablation lesion, the total ablation duration and final temperature, as well as complications associated with the

3 european urology supplements 6 (2007) Table 1 Summary of the study population and sites of treated metastases Liver Lung Kidney Adrenal gland Soft tissue Total no. Tumor volume reduction Tumor ablation Total number of ablations ablation procedure (bleeding, infection, pneumothorax) and rate of local recurrence as diagnosed on the follow-up CT scans were recorded. 3. Results With the exception of two pneumothoraces after treatment of two pulmonary metastases, which did not require further medical intervention, no other complications potentially related to the ablation process were observed. The mean observation time was 10 mo, with a median of 8 mo (range: 3 47 mo). None of the treated patients died during the observation period. In one patient with mediastinal lymph node metastasis of 3 cm in size, concomitant endoscopy was performed to be able to directly visualize the mucosal surface for potential thermal damage to the esophagus. All procedures relating to the complete ablation of the target lesion were successful, with exception of one patient in whom local recurrence was detected in the kidney on the first imaging control. Retrospective review of the CT scan performed immediately after the ablation procedure suggested incorrect needle placement during the ablation procedure (Table 1). The average metastasis size was 7.9 cm in the 7 patients treated for tumor volume reduction and 2.3 cm in the 31 patients treated for local tumor control (Fig. 1A and B). Five patients developed mild fever over a period of 2 d. The average ablation duration per metastasis was 11.5 min; a mean temperature of C was reached in the ablated lesion. On the immediate CT control scan, the total size of the ablated area ranged from 18 to 60 mm with a mean diameter of 30 mm. Regardless of tumor location, all patients were discharged without persisting pain; two patients revisited the emergency room within 1 d because of fever necessitating ultrasound to rule our liver abscess and CT scan of the chest for exclusion of pulmonary abscess or pleural empyema. 4. Discussion Percutaneous RFA represents an established option in therapy of metastases in many organs, including liver, lung, lymph nodes, soft tissues, and bones [6 8]. The underlying principle is local tissue coagulation through hyperthermia induced by Fig. 1 (A) Axial computed tomography (CT) slice with the ablation needle positioned within the pulmonary metastasis located in segment 4 of the left upper lobe. The image was acquired in CT fluoroscopy mode. (B) The 3-mo follow-up scan demonstrates the remaining pulmonary scar in a slightly different position due to the variation in inspiration depth.

4 656 european urology supplements 6 (2007) application of electromagnetic energy. The goal is the complete ablation of the neoplastic mass while sparing the surrounding tissue [9], similar to surgical resection. It has been shown that surgical resection of metastases in many malignant diseases may alter the course of the disease toward reduction of local complications by tumor growth, improved quality of life, or longer survival rates [10,11]. Advanced RCC may spread into many organs, which renders a surgical approach impossible. On the other hand, systemic therapy may be associated with severe side effects that limit its short- or long-term use. Particularly in patients with mixed response following immunotherapy, the clinician may be reluctant to change systemic treatment and a minimally invasive local treatment targeted at non-responding lesions would be desirable. RFA of primary RCC has been performed for many years, and results in the literature indicate that in certain patients, this type of tissue ablation is comparable to surgical resection [12]. However, data are missing on the technical success and complication rate of RFA for metastases originating from RCC. The degree of energy transmission into the tissue and the resulting size of ablation area depend on several factors, including the interstitial water content of the tissue and degree of perfusion. Although studies have shown that the size of the ablation lesion becomes greater if blood flow is reduced [13], we did not undertake means of local blood flow reduction because practical experience indicates that metastases from RCC are particularly suitable for thermal ablation with comparatively larger ablation areas than metastases with higher stroma content. It has been suggested that injection of saline into the target lesion results in a greater ablation area [14]; however, because every needle pass into the metastasis and increased pressure within the tumor potentially increase the risk of tumor cell dissemination [15], we refrained from concomitant injection during the ablation procedure. Several reasons speak in favor of the percutaneous ablation technique over surgical resection: RFA therapy can be repeatedly performed, it may be applied to outpatients (although in-house surveillance after the therapy is recommended), it involves fewer resources, and potentially it is less costly [16]. The proof of equivalence to surgical resection with respect to local recurrence, however, is not yet available. We analyzed the results of 66 RFA procedures performed in 38 patients referred for treatment of metastases from RCC. We preferred CT as the guiding technique over ultrasound due to the universal applicability in all organs including the lung, the possibility to monitor the ablation progress, and the use of CT for planning and follow-up controls. All patients took part in a standardized oncologic treatment program [17] and were presented in a local tumor board. If the metastasis to be treated was >5 cm in size, the intention for ablation was not complete local control rather than volume reduction. If these patients were excluded from the analyses, no recurrence occurred during the mean observation time of 10 mo. In one patient in whom a 1-cm metastasis in the kidney was noted on the first CT control scan 3 mo after the ablation, one could retrospectively see that the ablation needle shifted after placement and therefore complete ablation failed. In none of the patients did we observe hemorrhage or damage of the surrounding tissue; the two pneumothoraces were self-limiting and did not require further intervention. Because the local distribution of the heat within soft tissues cannot be controlled, several means exist to ensure that organs such as bowel loops, gallbladder, or nerves may be spared. In five patients, we injected up to 60 ml diluted contrast agents between the ablation target and the organ to be protected; although water conducts the heat better than fatty tissue, the displacement of the organs from the ablation target appeared to be of greater importance. In one patient with a lymph node metastasis in the posterior mediastinum, we opted to perform concomitant esophagoscopy because a displacement of the esophagus with water is hindered due the limited space in the posterior mediastinum. The injection of diluted contrast agents in this patient only served as a means of widening the access route to avoid passage through the lung. Our study indicates that RFA of metastases from RCC can be performed safely and with a low complication rate. The limitation of our study, however, is the low number of patients, the diversity of locations, and the limited period of time for follow-up observation. Nevertheless, the long-term success of RFA appears to depend mainly on complete ablation of the tumor that can be appreciated on the immediate CT control scan. Although necessary in only five patients, displacement of neighboring organs to prevent thermal damage seems to be a sensible approach. 5. Conclusion RFA seems to be a safe alternative option in the treatment of metastases from RCC and is associated

5 european urology supplements 6 (2007) with low complication rates. Overall, percutaneous RFA should be considered as a viable tool in the armamentarium of potential treatment options in selected patients with metastatic RCC. Acknowledgment The authors express their special thanks to Henning Meyer for helping with image selection and preparation, as well as Noga Rogalla for her support in writing the manuscript. References [1] Sutherland LM, Williams JA, Padbury RT, et al. Radiofrequency ablation of liver tumors: a systematic review. Arch Surg 2006;141: [2] 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 6-year period and ablation of 100 tumors. AJR Am J Roentgenol 2005;185: [3] Gervais DA, McGovern FJ, Arellano RS, et al. Radiofrequency ablation of renal cell carcinoma. Part 2: lessons learned with ablation of 100 tumors. AJR Am J Roentgenol 2005;185: [4] Matin SF, Ahrar K, Cadeddu JA, et al. Residual and recurrent disease following renal energy ablative therapy: a multi-institutional study. J Urol 2006;176: [5] Rogalla P, Juran R. CT fluoroscopy. Radiologe 2004;44: [6] de Baere T, Palussiere J, Auperin A, et al. Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation. Radiology 2006;240: [7] Steinke K, Sewell PE, Dupuy D, et al. Pulmonary radiofrequency ablation: an international study survey. Anticancer Res 2004;24: [8] Hiraki T, Yasui K, Mimura H, et al. Radiofrequency ablation of metastatic mediastinal lymph nodes during cooling and temperature monitoring of the tracheal mucosa to prevent thermal tracheal damage: initial experience. Radiology 2005;237: [9] Aron M, Gill IS. Minimally invasive nephron-sparing surgery (MINSS) for renal tumours. Part II: probe ablative therapy. Eur Urol 2007;51: [10] Vogl UM, Zehetgruber H, Dominkus M, et al. Prognostic factors in metastatic renal cell carcinoma: metastasectomy as independent prognostic variable. Br J Cancer 2006;95: [11] van der Poel HG, Roukema JA, Horenblas S, et al. Metastasectomy in renal cell carcinoma: a multicenter retrospective analysis. Eur Urol 1999;35: [12] Mouraviev V, Joniau S, Van Poppel H, Polascik TJ. Current status of minimally invasive ablative techniques in the treatment of small renal tumours. Eur Urol 2007;51: [13] Chang I, Mikityansky I, Wray-Cahen D, et al. Effects of perfusion on radiofrequency ablation in swine kidneys. Radiology 2004;231: [14] Lee JM, Kim SH, Han JK, et al. Ex vivo experiment of salineenhanced hepatic bipolar radiofrequency ablation with a perfused needle electrode: comparison with conventional monopolar and simultaneous monopolar modes. Cardiovasc Intervent Radiol 2005;28: [15] Gillams AR. Complications of percutaneous therapy. Cancer Imaging 2005;21: [16] Rohde D, Albers C, Mahnken A, et al. Regional thermoablation of local or metastatic renal cell carcinoma. Oncol Rep 2003;10: [17] Mickisch G, Carballido J, Hellsten S, et al. European Association of Urology: guidelines on renal cell cancer. Eur Urol 2001;40:252 5.