Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk

Authors


Osamu Ukimura md, Department of Urology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. Email: ukimura@koto.kpu-m.ac.jp

Abstract

Abstract  Objective:  Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia.

Methods:  Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20–53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3–6 months and an evaluation of metastasis was performed every 6 months.

Results:  At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma.

Conclusion:  Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.

Introduction

Radical or partial nephrectomy with open or laparoscopic surgery has been the standard treatment for renal cell carcinoma (RCC).1,2 However, the recent trend toward minimally-invasive surgery has served to accelerate the investigation of nephron-sparing treatment options, including thermal ablative technology with cryotherapy or radio-frequency ablation (RFA).3–6 Radio-frequency ablation induces ionic agitation and frictional heating, resulting in the coagulative necrosis of tumor cells. Although RFA for some selected human renal tumors has been successfully reported in the short term, the inability to achieve complete cancer cell death, preservation of renal function, imaging modality for treatment efficacy and the long-term oncological efficacy remain critical.7–10 Appropriate indication of any new treatment should be discussed before it can be considered as an established alternative therapy to traditional standard treatment. At the present time, our indication of RFA for RCC has been limited only to strictly selected patients who would be at operative and/or anesthetic risk undergoing traditional invasive surgical treatment requiring general anesthesia. We hereby report our preliminary experience with RFA for clinically localized renal tumors in nine carefully selected patients with complications in renal dysfunction and/or active diseases needing treatment in other organs. These patients were considered to have reason to avoid traditional invasive surgery for RCC under general anesthesia.

Methods

Patients with RCC who were deemed as having reason to avoid traditional invasive surgical treatment under general anesthesia and whose preservation of renal function was desired, were eligible for the present study. Informed consent was obtained from the patients and/or their families after explaining the limitations and risks of this treatment, including the possibly repetition of treatments and risk of metastasis during follow-up. This clinical study procedure was permitted by the Committee for Clinical Research on Human Subjects at the Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.

All of the nine selected patients (mean age, 67; range, 54–81 years) had complications that were considered to put them at significant operative and/or anesthetic risk for invasive surgery under general anesthesia, including solitary kidney, renal dysfunction, active poor-prognostic cancer in another organ, abdominal-aortic aneurysm, heart, lung, or brain diseases and/or advanced age. Patient characteristics are shown in Table 1. The mean diameter of the RCC was 38 mm (range, 20–53 mm).

Table 1.  Patient characteristics
CaseAge (years)Tumor sizeTumor locationFollow-up (months)Risk for surgery and anesthesia
  1. Lt, left; RCC, renal cell carcinoma; Rt, right.

16853 mmLt-central & peripheral,40Aortic aneurysm with pseudo cavity
25625 mmLt-peripheral21Glomeruri nephritis
36331 mmLt-close to renal hilum18Nephritic syndrome
45850 mmRt-central & peripheral18Bilateral RCC (Lt RCC of 108 mm)
57445 mmLocal recurrence15Ischemic heart & brain disease
68245 mmRt-peripheral12Bronchial asthma, heart disease
76240 mmLt-peripheral10Glomeruri nephritis, lung disease
86820 mmRt-peripheral 9Active liver cancer
97440 mmRt-peripheral 8Metastatic prostate cancer

The electro-surgical generator (Radionics, Cool-tip Radio frequency system, Century-MTI, Burlington, MA) delivered radio frequency energy (0–200 W, 480 kHz) through a 17 gauge (4.5 Fr) Cool-tip single straight electrode. The feedback algorithm of the generator continuously monitors tissue impedance, automatically adjusting output to maximize energy delivery. The output of energy delivery was at first manually determined to be 40 W for the initial minute and was 60 W, 80 W and 100 W thereafter for 1 min each, followed by an automatic feedback algorithm by monitoring impedance elevation of 20 ohm compared to the initial impedance over 12 min for one session of ablation. The estimated achieved therapeutic diameter was 28–42 mm. The patient was placed in the prone position, and thermal ablation was performed under epidural or local anesthesia, guided and monitored basically with ultrasound or optionally combined with computed tomography (CT). The treatment under ultrasound guidance was considered to be complete when the targeted lesion was covered with a hyper-echoic area of coagulative necrosis with a 0.5 cm rim of normal renal parenchyma around the tumor site. Once the ablation cycle is complete, a thermocouple at the electrode tip measures tissue temperature to confirm the efficacy of thermal ablation on the targeted coagulation zone. The end-point temperature of ablation was determined to be 60°C within the tumor. When this temperature elevation was not achieved, additional ablation was added. When the electrode was withdrawn after treatment, radio frequency energy was again delivered to cauterize the needle track in the renal parenchyma for approximately 1 min to prevent bleeding. Needle biopsy before the procedure was performed to confirm pathological diagnosis. Follow-up power Doppler ultrasound imaging, blood and urine tests were performed every 1–3 months and follow-up enhanced CT scans or magnetic resonance imaging (MRI) were evaluated every 3–6 months. Successful ablation was defined as no enhancement within the tumor area in 5 mm step sections of MRI/CT imaging. In patients with chronic renal failure or iodine-allergy, enhanced MRI was selected for evaluation. The residual enhanced area of the tumor was repeatedly treated. Evaluation of metastasis was performed every 6 months.

Results

In the present study, the risks for standard radical or partial nephrectomy, as well as general anesthesia, consisted of one or a combination of the risks which included chronic renal disease due to glomeruri nephritis, nephritic syndrome, solitary kidney, active cancer requiring treatment in another organ, ischemic heart disease, bronchial asthma, abdomino-aortic aneurysm, ischemic brain disease or idiopathic thrombocytopenic purpura. All patients were able to continue undergoing their respective treatments for active disease in other organs in parallel to the RFA treatment of RCC.

At a mean follow-up of 17 months (range, 8–40 months), seven (78%) of the nine patients had no evidence of enhanced lesions on imaging studies (complete response [CR]; Figs 1,2,3). The two cases with residual tumors were case 1, who had a large tumor measuring 53 mm in diameter, and case 5 with a symptomatic locally-recurring mass measuring 45 mm, both of which were in contact with or close to the bowel. Becuase case 1 also involved renal sinus, seven repetitions of this treatment with 3–6 months intervals achieved greater than 90% efficacy (Fig. 4). In this case, the residual part of the tumor contact with the bowel remained after the fifth ultrasound-guided RFA was targeted by real-time CT guidance for needle puncture to avoid injury to the bowel. Case 5, who had local recurrence of disease, contact with both the bowel and the psoas muscle and local pain complaints at 9 years after previous radical nephrectomy revealing pT3a disease, achieved the palliative effect of decreasing pain in addition to showing local control of the disease for 9 months with no evidence of enlargement by initial RFA. Subjective local pain sensations decreased on a visual analog scale from 6.6 (preablation) to 3.3 (postablation). However, at 12 months after initial RFA, progression of the disease (with no evidence of distant metastasis) was found to require repetition of RFA for the local recurrent tumor.

Figure 1.

(a) Case 3. Preoperatively-enhanced computed tomography (CT) demonstrated marked enhancement of solid renal tumor (31 mm in diameter) located close to the renal hilum. (b) Case 3. Postoperatively-enhanced CT showed complete disappearance of enhancement in the tumor with good preservation of normal parenchyma in contact with tumor.

Figure 2.

(a) Case 4. Preoperatively-enhanced computed tomography (CT) demonstrated marked enhancement of a right solid exophytic renal tumor (50 mm in diameter) in a patient who also had left T2 renal cell carcinoma (108 mm in diameter). (b) Case 4. Postoperatively enhance CT showed complete obliteration of the tumor identified by zero contrast enhancement.

Figure 3.

Case 2 (a) before and (b) during ablation. Intraoperative monitoring using gray-scale ultrasound was useful in confirming rough visualization of the lack of excessive extension of ablation in the normal parenchyma where nephron-sparing was attempted. Ultrasonic monitoring of the procedure was able to demonstrate the rough visualization of the treatment extension as a hyper-echoic area induced by micro-bubbles generated in the heating process.

Figure 4.

Case 1 (a) before and (b) after ablation. Disappearance of blood flow signals in the tumor, as well as preserved blood flow signals in the normal parenchyma where nephron-sparing was attempted, are demonstrated in the intra-operative power Doppler study.

Although the extent of the intraoperative therapeutic area could be roughly estimated using ultrasound imaging, a detailed extent of the therapeutic effects could not be evaluated by ultrasound imaging alone, resulting in the presence of a residual enhanced tumor after successful intraoperative ultrasound findings (Fig. 5). All patients had a short recovery time for being able to eat (within 6 h), except for one patient with minor transient gross hematuria and postoperative hemorrhage not requiring a blood transfusion. No analgesic administration was used post-ablation. There were no major complications, including urine fistula, stricture of the ureter or injury to surrounding organs. An increase of 0.49 mg/dL in serum creatinine levels was observed in one case who underwent RFA on a remaining solitary kidney following radical nephrectomy for RCC of the other kidney on the same day. Renal function of the other eight patients was well preserved, with no significant change in serum creatinine values (range, -0.2–+0.12 mg/dL; mean change, 0.05 mg/dL) when comparing pre- and post-ablation values.

Figure 5.

(a) Case 1. The involvement of the bilateral renal arteries by the pseudo cavity of large abdominal aneurysms was considered to be contraindication of surgical treatment of left renal cell carcinoma (53 mm in diameter). Enhanced magnetic resonance imaging (MRI) before ablation. (b) Case 1. The patient achieved a 92% disappearance of enhancement on the follow-up MRI, except for anterior and ventral parts of the tumor close to the bowel.

Intra-operative monitoring, using both gray-scale and power Doppler ultrasonography, was useful in confirming a rough visualization of the lack of excessive extension of ablation in the normal parenchyma where nephron-sparing was attempted (Fig. 5). Ultrasonic monitoring of the procedure was able to demonstrate a rough visualization of the treatment extension as a hyper-echoic area induced by generated micro-bubbles in the heating process. Intra-operative power Doppler study (Fig. 6) enabled the demonstration of the rough disappearance of blood flow signals in the tumor, as well as preserving blood flow signals in the normal parenchyma where nephron-sparing was attempted.

Figure 6.

(a) Case 8. Preoperatively enhanced computed tomography (CT) demonstrated marked enhancement of a solid renal tumor (20 mm in diameter) located at the upper pole. (b) Case 8. Postoperatively enhanced CT showed complete disappearance of enhancement in the tumor.

Discussion

In a clinical setting, it is not rare that patients with RCC have significant risks undergoing invasive surgery under general anesthesia and, if possible, need more minimally invasive treatment options. Although RFA still remains experimental because of the lack of long-term oncological efficacy, as well as possible incomplete tumor cell death,7,10 it has been extensively studied recently and, together with cryo-ablation, shows considerable promise.3–11 In the present study, RFA was well tolerated and minimally invasive with no significant deterioration of patients’ original risks for those with renal malignancy or for those at significant operative or anesthetic risk for invasive surgery under general anesthesia. Radio-frequency ablation also had a palliative effect for pain relief in one case of local recurrence. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment of RCC. Radio-frequency ablation can be repeated for suspicious residual tumors under local anesthesia, resulting in successful local control over a mean follow-up period of 17 months (maximum, 40 months) with neither significant complications nor distant metastasis.

Although RFA has been reported to be safe, Ogan et al. reported a critical case in multiple procedures for solitary kidney-induced acute renal failure.9 In the present study, although we performed multiple sessions to achieve therapeutic temperatures for the tumor in case 1 (with 3–6 months interval) and two cycles of the procedure during one session were performed in cases 3, 4 and 5 because the tumor was located centrally or close to the renal hilum, the renal function in these cases was well preserved. Although it has been reported to be difficult to achieve complete efficacy in those locations,6 we performed repetition of procedures in addition to real-time monitoring using ultrasonography to realize the ablative areas with the aim of achieving better therapeutic efficacy and fewer complications. As ultrasound is not a reliable monitoring modality when predicting microscopic tumor cell death, we agree that a more reliable monitoring system to predict the extension of tumor cell death by this treatment might be required. However, gray-scale ultrasonic monitoring of the procedure provided a rough visualization of the treatment extension as a hyper-echoic area induced by generated micro-bubbles in the heating process. In the present study, normal parenchyma contact with the tumor, even in a patient with renal dysfunction and a tumor located close to the renal hilum (case 3), was well preserved, as shown in Figures 2 and 5a. Ultrasound monitoring of the rough extension of ablation area seems to be useful in preserving renal function, as well in avoiding injury to the pelvis and ureter. Additionally, intra-operative power Doppler ultrasound enabled us to confirm the normal blood flow signals within the normal parenchyma where nephron-sparing was attempted. The appearance of blood flow signals evaluated by power Doppler ultrasonography can assist in determining rough efficacy immediately after thermal ablation of the targeted area. However, since there is currently no perfect imaging modality to prove the pathological success of this technique,6 repetition of follow-up enhanced imaging studies (CT or MRI) is necessary in assessing the long-term oncological outcome.

Since Zlotta et al. introduced RFA for renal cell carcinoma in humans in 1997,5 some clinical experiences of this treatment for selective patients with relatively small renal tumors have been published.6–11 As reported, the efficacy of this treatment for relatively large tumors, as well as for tumors with an involvement of the renal sinus is limited.6 The reported maximum size was a tumor of around 50 mm in diameter experienced by Graives et al.6 In the present series, a relatively large tumor (such as case 4, a tumor 50 mm in diameter) was satisfactorily ablated with two deliveries in a single session of this treatment. Radio-frequency ablation seems promising for the treatment of peripherally located tumors, even of relatively large sizes, by improving the technique. However, even though located peripherally, management for ventral or anterior parts of the tumor seemed to be limited and difficult to ablate totally because of the risk of injury to healthy tissue, such as the bowel. Further technical improvement is necessary for the management of a tumor close to the renal sinus or in contact with the bowel.

As mentioned, RFA is still an experimental treatment option for patients with RCC because of the lack of long-term efficacy and the possible limitation of incomplete tumor-cell death. Appropriate indication of any new treatment should be discussed before it can be considered as an established alternative therapy to the traditional standard treatment. At present, our indication of RFA for renal tumor has been limited only to strictly selected patients who were considered to have significant operative or anesthetic risks for traditional invasive surgery under general anesthesia and who had been given a detailed explanation of the possible limitations and risks of this treatment, including the possible repetition of treatments and risk of metastasis during follow-up.

In conclusion, in patients who are at significant operative and/or anesthetic risk or when the preservation of renal function and/or low-invasive treatment is desired, RFA could be an acceptable minimally-invasive therapeutic alternative for the local control of RCC with a mean follow-up of 17 months. Longer follow-up periods are required to evaluate the risks of local recurrence, needle tract seeding and metastasis. Intra-operative ultrasonography was able to visualize the real-time rough extension of the treatment, which must not extend too much to the normal parenchyma when nephron-sparing is attempted in patients with a high-risk of renal dysfunction.

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