Laparoscopic Radiofrequency Ablation of Small Renal Tumors: Long-Term Oncologic Outcomes

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1 LAPAROSCOPIC RADIOFREQUENCY ABLATION OF SMALL RENAL TUMORS: LONG-TERM ONCOLOGIC OUTCOMES Daniel Ramirez, Yun-Bo Ma, Selahattin Bedir, Jodi Antonelli, Jeffery Cadeddu, Jeffery Gahan Department of Urology UT Southwestern Medical Center Dallas, TX ªCorresponding Author: Jeffery Cadeddu, MD UT Southwestern Department of Urology Moss Bldg, 8 th Fl, Ste 112 5323 Harry Hines Blvd. Dallas, TX 75390-9110 Phone (214) 648-0202 Fax (214) 648-8786 [email protected] Running title: " Laparoscopic radiofrequency ablation of small renal tumors: Long-term oncologic outcomes." Key Words: radiofrequency ablation, small renal masses, laparoscopic ablative techniques Page 1 of 15 Journal of Endourology Laparoscopic radiofrequency ablation of small renal tumors: Long-term oncologic outcomes (doi: 10.1089/end.2013.0542) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

Transcript of Laparoscopic Radiofrequency Ablation of Small Renal Tumors: Long-Term Oncologic Outcomes

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LAPAROSCOPIC RADIOFREQUENCY ABLATION OF SMALL RENAL

TUMORS: LONG-TERM ONCOLOGIC OUTCOMES

Daniel Ramirez, Yun-Bo Ma, Selahattin Bedir, Jodi Antonelli, Jeffery Cadeddu, Jeffery

Gahan

Department of Urology

UT Southwestern Medical Center

Dallas, TX

ªCorresponding Author:

Jeffery Cadeddu, MD

UT Southwestern Department of Urology

Moss Bldg, 8th

Fl, Ste 112

5323 Harry Hines Blvd.

Dallas, TX 75390-9110

Phone (214) 648-0202

Fax (214) 648-8786

[email protected]

Running title: " Laparoscopic radiofrequency ablation of small renal tumors: Long-term

oncologic outcomes." Key Words: radiofrequency ablation, small renal masses, laparoscopic ablative techniques

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Abstract

Introduction: Unlike percutaneous radiofrequency ablation (RFA) of small renal tumors, there

is limited data assessing the long-term efficacy of laparoscopic RFA. Though the ablation

cannot be visualized as reliably as with cryoablation, laparoscopic RFA allows for improved

mobilization and placement of probes under direct vision. We reviewed our experience with

laparoscopic RFA to assess long-term oncologic outcomes.

Methods: We performed a retrospective study of all patients who had undergone laparoscopic

RFA for pT1a renal tumors from April 2000 to April 2010. Demographic, clinical and

radiologic data were assessed to determine indications and evidence for recurrence of disease.

Radiologic recurrence was defined as any new enhancement (> 10 Hounsfield units) after

absence of enhancement on initial negative 6-week computed tomography.

Results: Data was available for 79 patients who had 111 small renal masses treated over the 10

year period. The median tumor diameter was 2.2 cm and intraoperative biopsy identified renal

cell carcinoma in 77%. The median follow-up was 59 months with an estimated 5-year

recurrence-free survival of 93.3%. The overall rate of complications was 8.8% with a 3.8% rate

of major complications.

Conclusions: Long-term experience with laparoscopic RFA demonstrates that it is a safe and

effective option for the treatment of small renal tumors. Five year oncologic outcomes appear to

be comparable to extirpation.

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Introduction

The widespread use of cross-sectional abdominal imaging over the last twenty years has

increased the diagnosis of incidentally detected, low-stage renal tumors, resulting in a change in

their management.1,2

This development has prompted urologists to investigate less invasive

strategies aimed at maintaining local tumor control while preserving renal function and

improving patient quality of life outcomes.3,4

Renal tumor ablation, when compared to

extirpative treatment, has been associated with a low rate of complications, less morbidity and

improved recuperation. Recently, it has become an increasingly acceptable approach in

management of small renal tumors as the number of institutions performing renal mass ablation

is increasing. . A percutaneous approach, compared to laparoscopic, has historically been the

preferred method for the management of small renal masses undergoing radiofrequency ablation

(RFA) due to its less invasive nature. However, in certain scenarios, critical structures such as

ureter or bowel may exist in close proximity to the renal tumor. In these instances, a

laparoscopic approach may be necessary in order to mobilize these structures away from the

renal tumor thereby allowing direct visualization and delivery of ablative treatment. Currently,

the experience and follow-up of patients who have undergone a laparoscopic approach in the

radiofrequency ablation literature is limited.5-8

We reviewed our experience with laparoscopic

RFA to assess oncologic outcomes, safety and efficacy and provide the longest follow up in the

literature to date.

Methods and Patients

Institutional review board approval was gained to retrospectively review all patients who

underwent laparoscopic RFA from April 2000 to April 2010 at a single institution. There were

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a total of 80 patient identified who underwent laparoscopic RFA over this time frame. 79

of those patients had available clinical data and were included in the study. All patients

presented with an enhancing renal tumor seen on cross-sectional imaging and each elected to

undergo laparoscopic RFA. Intraoperative incisional biopsies (5 mm cup forceps) were obtained

routinely after ablation.8 Biopsy was done after ablation as a prior study from our

institution demonstrates that histological architecture is maintained in the tissue after

radiofrequency ablation is performed.9 Tissue samples were examined with hematoxyline-

eosin staining, and in some cases immunohistochemical staining was performed to assist in the

diagnosis.

All patients were treated with a Model 1500X Rita 250 watt radiofrequency generator

with Starburst XL probes (AngioDynamics, Latham, NY) as previously described. 8 Briefly,

probes were inserted percutaneously under laparoscopic guidance after exposure of the renal

tumor. Laparoscopic ultrasound was used to confirm proper probe deployment. The probe tines

were deployed 5-10 mm beyond the diameter of the lesion, and ablation was performed in two,

size-determined cycles to a target temperature of 105 degrees Celsius. A contrast-enhance

computed tomography (CT) scan was obtained 6 weeks post-operatively to confirm complete

ablation of the target lesion. Radiologic surveillance consisted of contrast-enhanced axial

imaging at 6 months, 12 months and at least annually thereafter. Pretreatment and follow up

serum creatinine and glomerular filtration rate (GFR) were obtained and recorded, as were

comorbidities, ASA score, age and post-operative pathology results.

Incomplete ablation was defined as residual enhancement of the target lesion at 6 weeks

of follow up. Recurrence was defined as an increase in tumor size or enhancement (> 10 HU) in

the vicinity if the treated tumor.

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Descriptive analysis was performed to characterize the patient population. Paired t test

was employed for evaluation of the changes in creatinine and eGFR after treatment. Estimated

GFR was calculated using the abbreviated MDRD equation. The Kaplan-Meier method was

used to determine estimated 5-year overall and recurrence free survival.

Results

Patient demographic data is listed in Table 1. Our patient population had a mean age of

63.8 years and a mean ASA score of 2.6. A total of 111 tumors in 79 patients were treated with

laparoscopic RFA. The mean size of the treated renal mass was 2.2 cm with a range of 0.9-4.2

cm. Six patients had solitary kidneys and 15 patients were diagnosed with pre-treatment

chronic kidney disease.

Table 2 lists perioperative outcomes. Mean OR time was 164 minutes (range 65-335

minutes) with a mean estimated blood loss (EBL) of 29 mL (range 0-400 mL). Mean length of

stay (LOS) was 1.8 days (range of 0-12 days). One patient required a 12-day hospitalization due

to a persistent ileus and ultimately was found to have renal pelvis obstruction. The overall rate

of complications was 8.8% (n = 7). Four (5.1%) of these complications were minor (Clavien

grade 1-2). Three (3.8%) complications were major (Clavien grade 3b) with 2 patients requiring

repeat surgery for obstruction of the collecting system at the ureteropelvic junction, 1 patient

requiring conversion to laparoscopic nephrectomy and 1 patient requiring stent placement for

urinary fistula. The mean tumor size of the patients with grade 3b complications was 3.2 cm.

The median follow up was 59 months. Two patients (2.5%) had incomplete ablation of

their lesions on follow up CT at 6 weeks and both patients were treated successfully with salvage

percutaneous ablation. Estimated 5 year recurrence-free survival was 93.3% with only 3 patients

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having recurrence of disease. The 2 patients with persistent enhancing lesions on follow up

imaging at 6 weeks were included in the recurrence-free survival calculation (Figure 1A). Of the

5 patients who had recurrence or persistent disease, the mean tumor size was 2.1 cm and the

mean and median time to recurrence were 55.5 months and 39 months, respectively. The 5-year

recurrence-free survival among the patients with biopsy proven RCC was 92%. Both 5-year

cancer-specific survival and metastatic-free survival were 100% in our cohort. Estimated 5-year

overall survival for our cohort of patients was 72% (Figure 1B). GFR data was collected during

pre-treatment evaluation and repeated at 12 months. Mean pre-treatment GFR was 65.9

ml/min/1.73m2 and 12 month mean post-treatment GFR was 62.0 ml/min/1.73m2 representing a

decrease in GFR of 5.8% over 12 months, though this change was not statistically significant.

Discussion

Within the realm of tissue ablation, different techniques have been implemented to target

renal tumors. In the cryoablation literature, a laparoscopic approach has been preferred over a

percutaneous approach. This may be because the expanding “ice ball” is easily visualized on

ultrasound, allowing for the identification of an adequate ablation margin. For RFA, this

relationship is reversed with more studies reporting a percutaneous technique as compared to a

laparoscopic one. The reasons for this are not clear; although the relative difficulty of RFA

probe placement with ultrasound guidance and the lack of a clearly defined ablation zone may be

contributing factors. Despite these drawbacks, a laparoscopic approach may be preferred for

RFA in certain situations where the proximity of critical structures to the renal tumor is of

concern. Laparoscopic RFA allows for the mobilization of the ureter, bowel and other

structures away from the ablation zone and theoretically ensures their safety. For this reason,

complications of in-situ ablation of small renal tumors have been relatively low.10-13

Within our

series, the overall complication rate was 8.8% with only 3.8% of patients suffering major

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complications (≥ Clavien grade 3). In contrast to the cryoablation literature, hemorrhage was not

an observed complication; however, 2 of the 3 major complications were related to injury to the

ureter or collecting system. The patients who suffered ureteropelvic junction obstruction

had tumors that were more anteriorly and medially located. These complications occurred

early in our series and as our experience progressed, patients with more medially located

tumors or tumors close to the collecting system were ultimately excluded from undergoing

laparoscopic RFA. The surgical complications encountered in our series were felt to be due

to direct use of the RFA probe and location of the tumor, not directly due to laparoscopic

dissection techniques.

Previous studies have reported similar complication rates. In 2004, Johnson et al

described a series of 139 cryoablations and 133 RF ablations and found an overall complication

rate of 11%, with 1.8% classified as major events.13

A meta-analysis by Novick et al reported a

4.9% incidence of major complications after cryoablation and a 6.0% rate of major

complications after RFA.14

While this and other data suggests that complication rates between

cryoablation and RFA appear similar, it has been widely reported that the risk of major urologic

complications is lower with ablative techniques when compared to either open or laparoscopic

partial nephrectomy.

As for oncologic outcomes of laparoscopic RFA, a recent series by Ji et al

demonstrated local tumor control in 98.1%. 6 Within our series, oncologic outcomes where

comparable with an estimated 5-year recurrence free survival of 93.3% and a 5-year metastatic

free survival of 100%. In comparison to percutaneous series, there appear to be no difference in

oncologic outcome measures.8 While the vast majority of RFA studies demonstrate favorable

oncologic outcomes, follow-up is limited and this is a common criticism of ablation therapy

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Thus the importance of this study which provides 5-year follow-up data (median 59 months)

demonstrating lasting efficacy for laparoscopic RFA.

Oncologic outcomes of RFA are often compared to extirpative therapy, with a somewhat

increased rate of local recurrence seen in RFA series. However, distant recurrence remains an

uncommon event using either technique with multiple studies confirming this result. Levinson et

al published one of the first long-term RFA reviews which demonstrated a 90.3% recurrence-free

survival and a 100% disease-specific survival 10

. Although recent data suggests that residual

tumor after local treatment may predispose patients to distant recurrence, this was not seen in our

series as no patients developed metastatic disease15

. This may be in part the result of

aggressively treating all patients with residual tumor (enhancement at 6 weeks) with immediate

re-ablation. Joniau et al showed that the success rate for RFA could be improved with repeated

ablations increasing from 86.9% after a single treatment to 93.8% after 2 or more treatments. 11

This ability to perform RFA in succession is an additional advantage of ablative therapies.

Indeed, our success rates for ablation approaches 100% when success after re-ablation is

considered. In addition, overall survival is similar between patient undergoing RFA and

those undergoing active surveillance for small renal masses.16,17

One of the purported advantages of tumor ablation over extirpative treatment is renal

function preservation. A recent study from The Cleveland Clinic reviewed 427 patients who

underwent robotic-assisted laparoscopic partial nephrectomy with a mean tumor size of 3.0

cm. They found a mean decrease in eGFR of 8% at a median follow up less than 18

months.18

We found a decrease in mean eGFR of 5.8% at 1-year follow up. Thirty percent

(N=24) of patients in our study had CKD stage 3 or greater prior to treatment such that

distinguishing the proportion of renal function loss from RFA versus the natural history of their

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pre-existing comorbidities was difficult. Nevertheless, there was no statistical loss in eGFR at 1

year. Multiple prospective reviews have shown a similar minimal effect of renal tumor RFA on

renal function.19,20

Several limitations of our study should be discussed. First, this was a retrospective study

making selection bias a concern, namely selecting for sicker, older patients as well as smaller

and anterior tumors. Also, the sample size is limited, however, when compared to previous

laparoscopic RFA series, the follow-up period is significantly improved. Another limitation of

this study is the analysis of renal function. Reporting renal function at one year may not truly

give insight as to the effect of nephron damage due to RFA; however, a longer follow-up would

allow competing risk factors to obfuscate the issue given a population with multiple co-

morbidities and preexisting CKD. Lastly, lack of contrast enhancement was used as a surrogate

for tumor destruction as opposed to ablation zone biopsy. Although this has been previously

debated, numerous studies support this as a suitable method for following patients after RFA.

Conclusion

Radiofrequency ablation through a laparoscopic approach is safe and effective in selected

patients. Long-term outcomes are excellent using this approach in terms of both local and distant

oncologic control and can be performed without a compromise to renal function.

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Table 1. Patient and Tumor characteristics

Patients No. 79

Total number of tumors 111

Single tumors 47

Multiple tumors 22

Bilateral tumors 10

Median Age (y) (range) 63.8 (18-35)

Mean ASA (SD) 2.6 (sd)

CKD ≥ 3 24

Mean Size (cm) (SD) 2.2 (sd)

Location No. (%)

Right 62 (55.9%)

Left 49 (44.1%)

Upper pole 26 (23.4%)

Mid pole 53 (47.7%)

Lower pole 32 (28.8%)

Anterior 55(49.5%)

Lateral 38 (34.2%)

Posterior 18 (16.2%)

Biopsy data No. (%)

RCC 61 (77.2%)

AML 6 (7.6%)

Oncocytoma 8 (10%)

Non-diagnostic 4 (5.1%)

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Table 2. Peri-operative outcomes

Mean LOS (days)

Mean OR time (min)

1.8 (0-12)

164.3 (65-335)

Mean Ablation time (min) 13.6 (3-32)

Overall Complications 7 (8.8%)

Minor (< Clavian 3) No. (%) 4 (5.1%)

Major (≥ Clavian 3) No. (%) 3 (3.8%)

Incomplete ablation No. (%) 2 (2.5%)

Recurrence No. (%) 5 (6.3%)

GFR (ml/min/1.73m2)

Mean Pre-treatment (SD) 65.86

Mean Post-treatment (SD) 62.02

Change in GFR, mean (SD) 3.84

Median follow up (months) (range) 59 (2-120)

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Figure 1. 5-year Disease-free Survival Curve

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Figure 2. 5-year Overall Survival

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