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Original Report |
1 Department of Radiology, Wake Forest University School of Medicine, Medical
Center Blvd., Winston-Salem, NC 27157.
2 Department of Urology, Wake Forest University School of Medicine,
Winston-Salem, NC 27157.
Received September 30, 2003;
accepted after revision December 10, 2003.
Address correspondence to R. J. Zagoria.
Abstract
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CONCLUSION. No serious complications occurred after 27 CT-guided radiofrequency ablation sessions in 22 patients. In total, no residual tumor was detected on follow-up contrast-enhanced CT or MRI 1–35 months (mean, 7 months) after final tumor ablation in 20 (91%) of 22 patients. Two patients with residual viable tumor deferred further treatment. Complete tumor ablation was achieved after a single treatment session in 83% of patients, and in 8% of patients after subsequent ablation sessions. Size was the major determinant for achieving tumor eradication with a single session of ablation, with all 11 tumors 3 cm or smaller being completely ablated after one session. Tumor location, histology, and the presence of renal disease did not correlate with treatment success. Contrast-enhanced CT performed immediately after ablation is reliable to exclude residual viable tumor. CT-guided radiofrequency ablation of renal tumors is safe and has a high rate of success in the treatment of small renal tumors, with no evidence of recurrence at midterm follow-up of treated patients.
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Frequently, the tumors being found in asymptomatic patients are smaller [4]. The traditional standard treatment for localized renal cell carcinomas is partial or radical nephrectomy, but this method is not ideal for treating all tumors because some patients are unable or unwilling to undergo surgery or would have limited or no functional renal tissue remaining after standard therapy. One possible alternative treatment for such patients is radiofrequency ablation [5–9]. We reviewed our experience with 22 patients who underwent radiofrequency ablation for renal neoplasms to evaluate complications, prognostic factors, and efficacy of treatment.
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Patient demographics, indications for choosing radiofrequency ablation, and tumor histology, location, and size were collected. The length of hospital stay, electrode type and size used, maximum tissue temperature attained at the end of the ablation, and the length of follow-up were recorded. All radiologic examinations for this study were reviewed by one radiologist. The tumors were classified as exophytic when more than 25% of tumor diameter contacted perirenal fat and central when the tumor extended into the renal sinus, using the classification system described previously [6]. For those patients who had MRI, enhancement of the tumor was measured without infusion and after gadolinium was administered on identical thin-slice 3D spoiled gradient-recalled acquisition sequences.
Before ablation, a history was obtained and a physical examination was performed. A metastatic tumor evaluation was also performed that included CT of the abdomen, chest CT or chest radiograph, and in some cases radionuclide bone scanning, depending on the preference of the referring urologist. The presence of coagulopathy disorders was excluded, laboratory values (levels of hemoglobin, hematocrit, WBC, blood–urea–nitrogen, and serum creatinine) were measured, and prophylactic antibiotics were given. Thirteen ablation sessions (48%) were performed with the patients given general anesthesia, and the remaining 14 sessions (52%) were performed with conscious sedation monitored by anesthesia personnel.
All ablations were accomplished percutaneously using CT guidance. During the procedure, a Cool-tip treatment probe (Radionics) was used with simultaneous infusion of chilled sterile water through the electrode. Three lengths of active electrode tip were used: a 2.5-cm-long electrode tip with a three-electrode cluster array and 2.0- and 3.0-cm-long single electrodes. The selection of tip length was based on tumor size. Electrode tips were selected to be as long as possible but not greater than 1 cm longer than the diameter of the tumor. An electrode probe with a 2-cm-long tip was selected for tumors 1 cm or smaller in diameter, and a 3-cm-long tip was chosen for tumors 1–2 cm in diameter. For tumors larger than 2 cm, a cluster electrode was used. CT guidance was used to place the radiofrequency probe in each renal tumor. The number of ablations performed in one session was based on the size of the tumor and the estimate that each ablation would destroy approximately a 2-cm-diameter area of tumor centered on the electrode. Multiple overlapping ablations were performed in an attempt to destroy the entire volume of the tumor. Each tumor received one to nine ablations (mean, 3) in a session for a maximum of 12 min per ablation. The radiofrequency generator was set on impedance control giving pulsed radiofrequency energy. Ablations were extended to the full 12 min unless the generator automatically switched to energy pulsing because of a rapid rise in tissue impedance more than twice per minute, indicating tissue boiling or charring and leading to diminished ablation. When this situation occurred, ablations were discontinued at the end of the next even-numbered minute over 6 min. Therefore, ablations lasted 6, 8, 10, or 12 min. Tissue temperature was recorded immediately after each ablation. If the tissue temperature was below 50°C, then another ablation was performed at the same site. Before reversing anesthesia, each patient underwent CT of the kidneys immediately after it was estimated, on the basis of the aforementioned parameters, that the ablation session was adequate for complete tumor destruction. If the serum creatinine level was 1.5 mg/dL or less, contrast-enhanced CT was performed.
After the ablation session and a brief period of observation in the postoperative anesthesia care unit, the patients were transferred to a hospital bed for observation overnight. During this time the patient's vital signs were monitored hourly, and a complete blood cell count was repeated 4 hr and 19 hr after the procedure if a significant change from the baseline values had occurred. Complications, both within the first 24 hr and long-term, were recorded. A mild perinephric hematoma was defined as bleeding that measured less than 1 cm on imaging, and a moderate hematoma was defined as greater than 1 cm, but not requiring transfusion. After tumor ablation, care of the patient was assumed by the referring urologic surgeon. A letter was sent to the referring physician recommending that follow-up contrast-enhanced renal CT or MRI be performed 1–3 months after the procedure.
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Fifteen tumors (63%) were located in the right kidney (upper pole, n = 5; lower pole, n = 4; interpolar, n = 6) and nine tumors (38%) were in the left kidney (upper pole, n = 1; lower pole, n = 5; interpolar, n = 3). Nine (38%) of the 24 tumors were classified as exophytic tumors; the remainder were central or mixed. Tumor size ranged from 1 to 7 cm (mean, 3.5 cm). Eleven tumors were 3 cm or smaller in diameter, and 13 tumors were greater than 3 cm in diameter.
The 2.5-cm cluster tip electrode was used in 16 ablation sessions (59%) and the 3.0- or 2.0-cm single-tip electrode was used for eight and three ablation sessions, respectively. A total of 81 separate ablations were performed during the 27 ablation sessions with the average tumor receiving three ablations (range, 1–9) in one session. A total of 24 ablations were performed on nine exophytic tumors, and each exophytic tumor received an average of three ablations. Forty of the 81 ablations lasted 12 min, and the remaining 41 ablations lasted 6–8 min. Maximum tissue temperature reached immediately after ablation ranged from 45°C to 81°C (mean, 55°C).
Patient follow-up ranged from 1 to 35 months (mean, 7 months). No metastases have been detected in any of the patients in this series. Contrast-enhanced CT (n = 12) or unenhanced CT (n = 15) was performed immediately after tentative completion of the ablation session.
Follow-up imaging was performed initially 1–3 months after the ablation session using helical CT with 5-mm collimation before and after IV contrast enhancement or with MRI. MRI was performed with a 1.5-T scanner and multiplanar T1- and T2-weighted acquisitions. Each MRI examination included thin-slice 3D spoiled gradient-recalled acquisitions before and after the IV injection of gadolinium. After ablation sessions, patients had one or more follow-up imaging studies, either contrast-enhanced CT (n = 12) or MRI (n = 15). On the first follow-up studies after 20 of the initial ablation sessions, patients showed no enhancement in the treated tumors. After four of the initial ablation sessions, patients showed enhancement in the tumors, interpreted as representing residual viable tumor.
Original tumor size in the four patients with residual tumor ranged from 3.1 to 4 cm in two cases and from 4.1 to 5 cm in two cases, with a mean size of 4.4 cm (Table 1, Fig. 1). Two patients with residual tumor had repeated ablation sessions at subsequent visits. One deferred repeated ablation because of coexisting advanced metastatic endometrial carcinoma, and one patient with enhancement was followed-up with surveillance only because of severe comorbidities. In total, no residual tumor was detected on follow-up contrast-enhanced CT or MRI in 20 (91%) of 22 patients treated with either one ablation session (18/22 patients) or multiple sessions (2/22 patients). Two patients had repeated radiofrequency treatment sessions to treat residual contrast-enhancing tumor. The first patient originally presented with a 5-cm tumor (Fig. 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H) and a creatinine level of 2.0 mg/dL. An unenhanced CT scan was obtained immediately after the first ablation session. Four months after the first ablation session, MRI showed a small area (1.2 x 1 cm) of contrast enhancement, with a 55% increase in enhancement after gadolinium infusion (Fig. 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H), located at the anterior and superior aspect of the original renal mass [6]. A second radiofrequency ablation session was performed with ablation focused on the area of residual tumor (Fig. 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H). Ten months after the second ablation session, follow-up enhanced MRI was performed and no enhancement was found in the tumor (Fig. 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H). The second retreated patient initially was found to have a 5-cm renal tumor after presenting with a femur fracture. Resection revealed a pathologic fracture related to metastatic renal cell carcinoma. The femur metastasis was resected before the kidney tumor ablation. Unenhanced CT immediately followed the first ablation session. The patient underwent a second radiofrequency ablation session because follow-up MRI performed 1 month after the first ablation session showed a 3-cm area of enhancement in the tumor bed, suggesting residual disease. A third radiofrequency ablation session was performed 12 months after the second ablation because follow-up MRI showed a small area of enhancement at the periphery of the mass. Three and 10 months after the third ablation session, repeated MRI showed no enhancement at the site of the original renal mass.
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The rate of successful complete tumor ablation was correlated with various tumor parameters. The success rate for complete ablation of all clear cell carcinomas was 79% (11/14), with the three incompletely ablated tumors measuring 4, 5, and 5 cm. For papillary carcinomas, the success rate was 100% (2/2), and for oncocytic neoplasms it was 100% (2/2). The success rate for complete ablation of tumors in patients with an elevated serum creatinine level was 60% (6/10). The success rate for complete ablation of tumors in patients with a normal serum creatinine level was 82% (14/17), with the incompletely treated tumors in this group of patients being 3.7, 4, and 5 cm in diameter. The success rate for complete ablation of tumors less than 3 cm was 100% (11/11), and for those greater than 3 cm was 69% (9/13) (p > 0.05).
Contrast-enhanced CT was used to assess residual tumor viability in patients with normal serum creatinine levels. No patient had residual tumor detected on a later scan when the immediate contrast-enhanced scan showed no tumor enhancement (Fig. 3A, 3B, 3C, 3D). When we found enhancement on contrast-enhanced CT immediately after tentative completion of an ablation session, we treated the enhancing areas with additional ablations. Two of 12 patients, with immediate contrast-enhanced CT showing areas of tumor enhancement, received additional ablations before termination of the treatment session. In the patients who received extra ablations on the basis of the presence of residual enhancing tumor, a second bolus of IV contrast material was not injected because a full dose had already been administered. Therefore, the adequacy of the additional ablations could not be immediately assessed. In 15 patients only unenhanced CT was performed immediately after an ablation session to assess complications. Four patients showed residual tumor on the follow-up imaging performed at a later date after an ablation session. Three of them had only an unenhanced CT performed at the end of the ablation session, and one had contrast-enhanced CT and additional ablations immediately afterwards.
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Complications reported within the first 24 hr were mild pain (4/27 ablation sessions, 15%), mild perinephric hematoma (9/27, 33%), mild pain and pneumothorax (1/27, 4%), and mild pain and perinephric hematoma (3/27, 11%). The remaining 10 ablation sessions had no complications. No complications required intervention or prolongation of hospital stays. No patients with hematomas required transfusions. No additional complications were found on follow-up clinical or radiologic evaluations. In two patients with solitary kidneys, one had a perirenal hematoma and one had no complication. The length of stay in the hospital was less than 24 hr after 27 ablation sessions, 2 days for four ablation sessions, and 3 days for one session. Hospitalization was prolonged over 1 day only for patients with serious comorbidities requiring hospitalization for reasons other than for ablation-related problems.
Ten of 22 patients had an abnormal serum creatinine level (1.6–3.1 mg/dL) before radiofrequency ablation. Eight of them showed stable or slightly decreased serum creatinine levels after ablation. Two patients with creatinine levels of 3.2 and 1.8 mg/dL had increases to 3.3 and 2 mg/dL, respectively. In four (15%) of 27 ablation sessions, patients showed elevated WBC (range, 11.2–12.8 x 103/µL) that returned to normal within 24 hr.
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The success rate of radiofrequency ablation in treating renal cell carcinoma is largely dependent on tumor size. In this study, tumors smaller than 3 cm in diameter had no imaging evidence of residual viable tumor after a single ablation session. Residual tumor was found only in patients with tumors greater than 3.1 cm, and 31% of the tumors showed residual tumor after initial treatment. This finding suggests that larger tumors are more difficult to eradicate completely with radiofrequency ablation.
The risk of incomplete tumor eradication mainly depends on tumor size. All residual viable tumor tissue occurred in patients in whom the original renal mass was greater than 3 cm in diameter. No tumors 3 cm in diameter or smaller had residual or recurrent tumor found during the follow-up period in our study. The second factor to affect incomplete ablation of tumor is whether contrast material was used for CT immediately after ablation. Immediate postablation contrast-enhanced CT was useful in detecting residual tumor by showing enhancement, which led to additional ablations before terminating the treatment session. However, 10 (45%) of 22 patients had abnormally elevated levels of serum creatinine and were not eligible for the use of IV contrast material. In patients with a high serum creatinine level, in whom only unenhanced CT was performed after ablation, these scans were not adequate for assessing the presence of residual viable tumor tissue. MRI to assess residual renal cell carcinoma soon after ablation is suggested to detect residual tumor.
Other parameters that may affect the success of radiofrequency ablation are the surrounding tissue, tumor location, and vascularity of the tumor. Central tumors, surrounded by vascular renal parenchyma, are more difficult to treat than exophytic tumors, which are partially surrounded by avascular perirenal fat [6]. Fat has an insulating effect and thus increases the temperature that can be reached in the tumor [6]. In one study, all five exophytic tumors (100%) and two (50%) of four central tumors were free of enhancement at follow-up [6]. The central tumors were larger than the exophytic tumors in that study, with a mean size of 3.8 versus 2.6 cm [6].
Surrounding fibrosis, as seen in kidneys with chronic renal disease [11], is also expected to reduce thermal conduction and heat dissipation, thus improving tumor treatment [6]. Another possible reason for ablation failure is that highly vascular tumors, such as clear cell carcinomas and oncocytic neoplasms of the kidney [12], may not reach lethal temperatures during ablation. The increased blood flow in the tumor may act as a heat sink that rapidly distributes the heat away from the tumor, thereby diminishing the effect of the treatment.
We found that the tumor location, exophytic or central, had no influence on eradication at follow-up. In our study, seven (78%) of nine exophytic tumors were free of enhancement and two exophytic tumors showed enhancement on follow-up examination. The tumors showing enhancement, either exophytic or central, were larger. Tumor size was the major determinant of treatment success, independent of tumor location, tumor histology, and preexisting renal insufficiency. In our study, the only parameter that correlated with success of radiofrequency ablation was tumor size. Tumor histology, a correlate of tumor vascularity [12], and vascularity of tissue surrounding the tumor, with renal parenchyma in patients with chronic renal disease being more fibrotic and less vascular than normal renal tissue [11], did not affect the success rate for renal tumor ablation.
One advantage of radiofrequency ablation is the low rate of serious complications. Studies have shown that radiofrequency ablation of renal cell carcinomas has minimal (7–17%) complications [5, 8]. Our study showed that after 17 treatment sessions (63%), patients had mild or moderate complications. Although the complication rate was higher (63%) in our study than reported in others (7–17%) [5, 8], this finding seems to be largely attributable to the abnormalities that are counted as complications. All complications in this study were clinically insignificant. No long-term or clinically significant complications occurred. We did detect transient elevation of the WBC in five sessions (19%), presumably because of demarginalization of these cells stimulated by the stress of the ablation procedure. In one report, three of four complications occurred in patients with a solitary kidney [8]. We treated two patients with a solitary kidney, and neither had a significant complication. Our sample size was limited; the correlation between solitary kidney and complications needs further study with a larger sample size.
One limitation of our study is that the outcomes of radiofrequency ablation are typically measured in terms of contrast enhancement on follow-up imaging, with a lack of enhancement implying that no viable tumor remains [13]. Our end point for successful treatment was the absence of contrast enhancement on follow-up contrast-enhanced CT or MRI. Lack of enhancement on imaging follow-up has generally been assumed to mean lack of viable tumor. However, this belief may not always be true. In one study, pathologic examination revealed residual viable tumor foci in 5% of the volume in seven of nine treated renal tumors [14]. This finding was thought to be caused by skip areas in the tumors that survived the ablation procedure. Another in vivo study in which renal tumor ablation was performed using the device and technique used in our clinical study, but a different ablation device than the one used in the study showing skip areas of viable tumor, showed uniform tumor devitalization without skip areas [15]. Hence we believe that lack of contrast enhancement on CT or MRI indicates complete tumor eradication, but follow-up surveillance imaging is warranted because long-term results for renal tumor radiofrequency ablation are lacking, and later scans should be used to detect metastatic or metachronous lesions.
Radiofrequency ablation could prove to be a useful treatment for patients who are not ideal surgical candidates. The success of radiofrequency ablation was primarily influenced by the size of the tumor in this study. Renal cell carcinomas smaller than 3 cm can be reliably eradicated with percutaneous CT-guided radiofrequency ablation, regardless of the tumor location, histology, and presence of surrounding normal kidney. The presence of radiologically detected residual disease on follow-up scans does not necessarily indicate a poor outcome for the patient because residual tumor can be retreated and there does not appear to be a high risk of systemic spread from foci of residual tumor. No patients in our or other published series have developed detectable metastatic disease after incomplete renal tumor ablations (followup range, 1–42 months) [5–8].
Additional long-term data regarding local and systemic relapse and survival are needed before the oncologic efficacy of this technique can be verified for therapy of small low-stage renal cell carcinomas. Current findings suggest it is an acceptable alternative in restricted patient populations.
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