Comparison of Percutaneous and Laparoscopic Renal Cryoablation for Small (<3.0 cm) Renal Masses

Abstract

Purpose:

We reviewed our experience with laparoscopic cryoablation (LCA) and percutaneous cryoablation (PCA) in the management of small renal tumors and compared clinical outcomes, short-term oncologic results, and patient complications.

Patients and Methods:

A retrospective comparison of two prospectively collected oncologic databases was performed. Ninety patients underwent PCA for 99 lesions and 81 patients underwent an LCA for 97 lesions. Patient characteristics, perioperative data, and tumor characteristics were recorded including age, estimated blood loss, complication rate, tumor size, and tumor pathology.

Results:

Patients in both the PCA and LCA groups had similar demographic and tumor characteristics. The PCA group had two major complications (2%), and the LCA group had three major complications (3.7%) (P = 0.374). In the LCA group, estimated blood loss was associated with tumor location with hilar tumor demonstrating a significantly higher mean blood loss (191 mL) compared with endophytic, mesophytic, and exophytic tumors (70 mL, 71 mL, 73.5 mL), respectively (P = 0.05). Malignancies rated in the PCA and LCA groups were 50.5% and 60.0%, respectively (P < 0.05). In the PCA group, nine (9.1%) patients demonstrated treatment failure with a persistent enhancement in the ablation bed. All nine were treated with a subsequent PCA. One patient had subsequent tumor bed enhancement and underwent an open radical nephrectomy. Treatment failed in three (3.1%) patients in the LCA cohort (incomplete ablation or recurrence).

Conclusions:

With short-term follow-up, both LCA and PCA are safe and effective treatments for small renal masses. Patients undergoing PCA had a reduced hospital stay and a lower surgical complication rate, albeit with an elevated re-treatment rate. Long-term data is needed to establish long-term oncologic efficacy. Renal function did not significantly change in patients after cryoablation, including patients with a solitary kidney.

Introduction

M inimally invasive nephron-sparing treatment modalities and new technology have changed the management of small (<3.0 cm) renal cortical neoplasms. These technologies focus on three primary objectives: Oncologic efficacy, nephron preservation, and low morbidity. At present, open partial nephrectomy (OPN) is the surgical standard of care for the management of small renal masses (SRM) and has demonstrated similar perioperative and oncologic benefits when compared with radical nephrectomy for tumors ≤4 cm.^1
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The introduction of ablative technology in the form of radiofrequency ablation and renal cryoablation provides additional minimally invasive alternatives for the management of SRMs. Cryoablation can be performed by either a laparoscopic (LCA) or percutaneous approach (PCA). PCA is performed typically under CT guidance and is usually indicated for lateral and posteriorly located tumors. In the present study, we compare our cryoablation experience with both LCA and PCA, and report our short-term clinical and oncologic outcomes.

Patients and Methods

A retrospective comparison of two prospectively collected oncologic databases from two institutions was reviewed. Between January 2005 and July 2008, 171 patients underwent either PCA or LCA for renal cortical neoplasms ≤3.0 cm. Ninety patients underwent PCA for 99 renal masses by two surgeons (BWS) and (JL). Eighty-one patients underwent LCA for 97 renal masses by a single surgeon (JL). The indication for renal cryoablation was a localized, enhancing renal mass on preoperative CT or MRI. Patient demographics and procedure details were recorded, such as age, tumor size, histopathology, length of hospital stay, serum creatinine, and complication rates.

Lesions were classified based on their location within the renal parenchyma as being exophytic, endophytic, and mesophytic. Exophytic tumors have more than 60% of their mass outside the natural kidney contour. Endophytic tumors have greater than 60% of their mass within the natural border of the kidney, and mesophytic tumors have 40% to 60% of their mass in either direction.⁴ Renal masses located within 5 mm of the main renal vessels were classified separately as hilar tumors. In the LCA group, either a transperitoneal or retroperitoneal approach was chosen, depending on tumor location. Complications were defined as major and minor and were classified based on the Clavien classification system.^5,6

Laparoscopic cryoablation

LCA was performed in patients with either an anteriorly or posteriorly located renal mass. All patients with a hilar tumor underwent an LCA. Two percutaneous biopsies are performed before the start of the procedure. An 18-gauge, 25-cm core-biopsy instrument (C.R. Bard Medical Division, Covington, GA) is placed percutaneously through the abdominal wall. The biopsy sites are chosen at random. The needle is placed on the surface of the tumor, and the biopsy gun is engaged, obtaining the biopsy sample.

A double freeze-thaw cycle was performed in each case using 17-gauge (1.47 mm) probes (IceRods, Galil Medical, Minneapolis, MN). The ice ball was perpetuated until it completely engulfed the renal tumor as well as a margin of normal renal parenchyma. In all cases, intraoperative laparoscopic ultrasonography (BK Medical Systems Inc, Peabody, MA) was used to monitor adequate depth of the lesion and the number of probes needed to ensure complete ablation. Each freeze cycle was terminated once an ice ball large enough to cover the lesion was seen on ultrasonography. If the lesion did not appear to be adequately treated by the first freeze cycle, additional ice rods were placed in the region of the tumor before the second freeze cycle. An active thaw cycle was used between the two freeze cycles, and a second short thaw cycle was used to safely remove the cryoablation probes.

All cryoablated masses were biopsied intraoperatively before cryoablation. For hilar renal masses, efforts were made to preserve the renal vasculature. If a 1-cm margin could not be achieved, the main renal artery or an appropriate segmental branch was clamped with laparoscopic bulldog clamps (Klein Medical, San Antonio, TX). If complete ablation of the target lesion did not occur, additional ice rods were deployed, or the freeze cycle time was extended.

Percutaneous cryoablation

All patients undergoing PCA had a posteriorly located renal mass. Anterior lesions were contraindicated because of the risk of adjacent organ injury and the inability to accurately place the ice rod probes. All patients undergo CT with intravenous (IV) contrast before the procedure. All patients treated with a PCA had posterior tumors. The patient is placed in a prone position and IV sedation is administered. A targeting template (fast find grid; Webb manufacturing, Philadelphia. PA) is placed on the patient's ipsilateral flank and noncontrast CT is performed. The template allows for cephalocaudal marking of the skin so that the site of percutaneous access can be chosen. Next, 1% lidocaine is used as a local anesthetic before access sheath and probe insertion. Sedation consists of a combination of midazolam (up to 5 mg IV) and morphine (10 mg IV). All patients are monitored during the procedure for hemodynamic stability.

After sedation, we place an “access sheath” of a 14.5 gauge Osteocut biopsy needle (C.R. Bard Inc, Tempe, AZ) (deployed at the previously marked cephalocaudal location) and estimate the angle for proper needle targeting from the targeting CT scan. An access sheath is placed before deployment of all probes. Ideally, the access sheath is to be deployed within the Gerota fascia just outside the renal tumor. Use of an access sheath is valuable because it helps to assure excellent targeting for the biopsy and the ablation probe placement despite movement of the kidney. Percutaneous biopsies are performed using an 18-gauge A.C.T. biopsy needle (Temno/Cardinal health, Dublin, OH).

The cryoprobe(s) are then deployed through the same access sheath(s) and a final CT scan is performed to confirm that the needles are in perfect position (just beyond deep margin of the tumor). A standard double freeze/thaw cycle is performed. The ice ball geometry and extension is actively monitored with CT. Toward the end of the first freeze cycle, a half dose of IV contrast is administered, and a CT is performed to assure that the ice ball has extended at least 1 cm beyond the tumor in every dimension. Another half dose of contrast is administered after the second freeze cycle when the ablation probes (but not the access sheaths) have been removed. If complete ablation of the target is not achieved, additional probes may be deployed to assure complete ablation.

Follow-up

Follow-up consisted of a telephone interview 1 week postoperatively to assess general recovery status and discuss biopsy results. Three months after cryoablation, patients underwent imaging with contrast-enhanced CT or MRI. Additional imaging occurs at 6 and 12 months postoperatively, with annual imaging thereafter. MRI was used in cases of renal insufficiency. Treatment failure was defined as enhancement of the tumor bed or growth of the cryoablated site and characterized as an incomplete ablation (≤6 months from time of procedure) and recurrence (>6 months).

Statistical analysis

Statistical analysis was performed using SPSS v. 13 (SPSS, Chicago, IL). The Student t test and the Fisher exact test were used to analyze the data. A P value of <0.05 was considered statistically significant.

Results

One hundred and seventy-one patients underwent cryoablation between January 2005 and July 2008 at the two institutions. Ninety patients underwent a PCA for 99 renal lesions and 81 patients underwent an LCA for 97 tumors. In the LCA group, 67 (69%) procedures were performed using a transperitoneal approach and 30 (31%) procedures with a retroperitoneal approach. The mean patient ages were 67 and 69 years for PCA and LCA, respectively (P = 0.174). The mean tumor size on preoperative CT or MRI was 2.1 cm for the PCA group and 1.9 cm for the LCA cohort (P = 0.126). Fourteen (15.5%) patients who underwent PCA and 9 (11.1%) who had an LCA had a solitary kidney (Table 1).

Table 1.

Patient and Tumor Characteristics

	PCA	LCA	P values
No. patients	90	81
No. lesions	99	97
Mean age	67	69
Preop Cr (mg/dL)	1.2 (±0.5)	1.2 (±0.5)	0.348
Postop Cr (mg/dL)	1.05 (±0.5)	1.24 (±0.7)	0.451
Mean tumor size (cm)	2.1 (±0.7)	1.9 (±0.7)	0.135
Right	36 (42.3%)	57 (58.8%)
Left	49 (57.6%)	40 (41.2%)
Exophytic	20 (23.5%)	44 (45.4%)
Mesophytic	7 (8.2%)	21 (21.6%)
Endophytic	16 (18.8%)	22 (22.7%)
Hilar	n/a	4 (4.1%)
Uncharacterized	42 (49.4)	6 (6.2%)
Patients with solitary kidney	14 (15.5%)	9 (11.1%)

PCA = percutaneous cryoablation; LCA = laparoscopic cryoablation; preop = preoperative; Cr = creatinine; postop = postoperative.

The mean preoperative serum creatinine levels for the PCA and LCA groups were 1.2 mg/mL and 1.2 mg/mL, respectively (P = 0.348). The average postoperative creatinine level was 1.05 mg/mL and 1.24 mg/mL (P = 0.451) in the two groups. The average preoperative and postoperative creatinine level for patients with a solitary kidney was 1.1 mg/mL and 1.25 mg/mL (P = 0.351), respectively. The mean freeze time was 21.5 minutes for PCA and 15.6 minutes for LCA (P = 0.06), and the average hospital stay for PCA and LCA patients was 0.1 days and 1.5 days (P = 0.001). The mean estimated blood loss in the LCA group correlated with tumor location. Hilar tumors trended toward more hemorrhage compared with other tumor locations. Average blood loss for hilar tumors was significantly higher (191 mL) (P = 0.05) compared with endophytic, mesophytic, and exophytic locations (70 mL, 71 mL, 73.5 mL).

The majority of patients are discharged from the hospital on postoperative day (POD) 1 and usually do not need narcotic pain medication at discharge. Two (2%) major complications occurred in the PCA group. The first patient had a diagnosis of pneumothorax after the procedure and was subsequently treated successfully with a chest tube. This patient was discharged without long-term sequelae. The second patient had evidence of a myocardial infarction postoperatively and was discharged on POD 8.

Three (3.1%) major complications occurred in the LCA cohort as significant hemorrhage secondary to postablation tumor fracture necessitating transfusion. One of the patients was given a transfusion intraoperatively and was converted to laparoscopic partial nephrectomy (LPN) to control the bleeding. The other two patients needed intraoperative transfusion because of the amount of blood loss, but conservative management was used after the procedure and conversion or subsequent transfusions were not necessary. No patient in the PCA cohort needed transfusion, surgical conversion, or embolization. No patients were converted to open surgery or to radical nephrectomy.

Intraoperative biopsy results demonstrate a malignancy rate of 50.5% for the PCA group and 60.0% for the LCA group (P < 0.05). In the LCA group, clear-cell carcinoma was diagnosed in 36 (61.1%) lesions, papillary in 20 (33.9%), and chromophobe in 3 (5%). Thirty-nine lesions (40%) were benign, including 19 oncocytomas (19.6%), 4 angiomyolipomas (4.1%), and 16 (16.3%) fibrous or adipose tissue. In the PCA group, 32 (36.8%) biopsy results were nondiagnostic. The histopathologic subtypes of renal-cell carcinoma (RCC) were not available because these data were not included in the prospective PCA database approved by the Institutional Review Board. In addition, nine (10.3%) benign tumors were identified: 6 (7.2%) oncocytoma, 3 (3.1%) angiomyolipomas. Biopsy was not performed in two renal masses.

The median follow-up was 11.0 months for PCA and 12.0 months for LCA. There were nine (9.1%) incomplete ablations in the PCA cohort with persistent contrast enhancement during the first 6 months of follow-up. The pathology results for these patients was not recorded. All nine underwent a second cryoablation. One tumor was found to have persistent enhancement on CT after the second PCA, and the patient ultimately underwent an open radical nephrectomy. The final pathology results revealed clear-cell RCC.

One tumor (1%) in the LCA group was observed to have an incomplete ablation. Enhancement developed in this patient at the ablation site 4 months after the procedure, and the patient was subsequently treated with an OPN. The final pathology results revealed a conventional (clear-cell) RCC that was excised with a negative margin. At 31 months follow-up, no evidence of disease has been identified. On CT scan 12 and 18 months after the procedure, two patients undergoing LCA showed a recurrence at the ablation site. The first patient received a second ablation with no evidence of recurrence 7 months after the repeated procedure. The second patient was lost to follow-up with no additional information available. No patient undergoing PCA has had a local recurrence, and no recorded cancer-specific deaths have occurred in either group.

Discussion

Advances in minimally invasive surgery have changed the way SRMs are being managed. With the introduction of ablation technologies, a number of different modalities are being evaluated. Currently, evidence is growing in support of the safety and efficacy of renal cryoablation. Previously, cryoablation has been suggested as an option for patients with an anatomic or functional solitary kidney, high-risk surgical candidates, or in patients with a short life expectancy. Recently, the indications for renal cryoablation have expanded as a treatment option for selected healthy patients. Cryoablation offers a nephron-sparing alternative that can obviate the need for an extensive hilar dissection and vascular occlusion. Tissue destruction occurs from sequential freezing and thawing of tissues.^6

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Studies have been published on renal function as an outcome variable after partial nephrectomy or cryoablation. In addition, studies support the application of cryoablation in patients with a solitary kidney because of the negligible effects on renal function.^10,11

In the current study, 19 patients with a solitary kidney underwent cryoablation for 21 tumors. These patients all had successful management of their tumors without significant alteration in their renal function, further supporting the application of ablation in the setting of a solitary kidney (P = 0.351). In a recent comparison of ablative modalities and LPN in patients with solitary kidneys, ablation resulted in substantially less diminution of renal function.¹²

Overall, the complication rate was low for both procedures. There were 2 (2%) major complications (Clavien grade IIIb) in the PCA group. Estimated blood loss was low in both groups. Mean blood loss in the LCA group varied with respect to tumor location, revealing that hilar tumors trended toward greater blood loss compared with other locations. Previous study has shown that the surgical management of hilar lesions can pose a challenge even for the experienced laparoscopic surgeon.¹³ In these cases, we perform a hilar dissection, and all preparations are made for LPN in case it is necessary to control bleeding.

Our study confirms that PCA is associated with a substantially shorter length of hospital stay compared with LCA (P < 0.001). Bandi and colleagues¹⁴ showed that PCA was associated with a shorter mean anesthesia time (P = 0.001), shorter mean hospital stay (P = 0.007), and shorter time to complete recovery (P = 0.05) compared with patients undergoing LCA.

The PCA group was associated with a greater number of incomplete ablations (9.1%) compared with LCA (1%). This difference may be related to the method in which the ice rods were placed. In LCA, the probes are placed under direct vision, which may lead to a more accurate estimate of the overall number of probes needed as well as proper spacing of the probes to fully ablation the tumor. In addition, intraoperative ultrasonography is used to confirm depth of placement. Although probes are placed with CT guidance in PCA, it is more difficult to assess the number of probes needed. In our series, the cancer-specific survival rate in our series for both groups was 100%.

The major limitations of this study are the retrospective design and limited follow-up. Despite the advancements in targeting technology and the short-term published data on PCA, its role in the management of SRM remains controversial. Because it is a relatively new modality, it is imperative to evaluate long-term results with a larger number of patients to properly determine the true role of SRM ablation in urologic practice.

Conclusions

Although renal cryoablation is effectively performed by either a laparoscopic or percutaneous approach, PCA demonstrates a higher failure rate. Accuracy in targeting the renal tumor may be more difficult using only an image guidance approach (PCA). Hospital stay and complications, however, are significantly less in the PCA group. Renal function did not significantly change in patients after cryoablation, including patients with a solitary kidney.

Footnotes

Disclosure Statement

Dr. Jaime Landman, research support and consultant to Galil Medical. No competing financial interests exist for the other authors.

Abbreviations Used

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