Mini Review
Radiofrequency Ablation in Renal Cell Cancer: Review
Yüksel M1, İpekçi T2 and Hoşcan MB3*
1Department of Urology, Antalya Training and Research Hospital Antalya, Turkey
2Department of Urology, Baskent University, Turkey
3Department of Urology, Medstar Topçular Hospital, Turkey
*Corresponding author: Mustafa Burak Hoşcan, Department of Urology, Medstar Topçular Hospital, 07400 Alanya-Antalya, Turkey
Published: 25 Jul, 2016
Cite this article as: Yüksel M, İpekçi T, Hoşcan MB.
Radiofrequency Ablation in Renal Cell
Cancer: Review. Clin Oncol. 2016; 1:
1033.
Abstract
Renal cell cancer is the most fatal urologic cancer which is diagnosed at the metastatic stage in 20-
30%. Generally small-sized renal masses are defined as slowly progressing masses with a size of ≤4
cm and have a good prognosis. As a result of the improvements in USG, CT and MRI technologies,
incidental tumor determination ratio has increased in course of time. The gold standard treatment
for small-sized renal masses is open/laparoscopic/robotic partial nephrectomy. RFA is a minimal
invasive therapy method which is a good alternative to surgery in elder comorbid patients or
the patients with genetic predisposition for multiple tumors or patients with bilateral tumors or
patients with a solitary kidney. In this review we want to discuss technique, overall outcomes and
complications of RFA and compare its efficacy with surgery and cryoablation according to the
current literature.
RFA is a good alternative treatment method for the RCC’s smaller than 4 cm with an oncologic
efficiency closer to nephron protecting surgery and with lower complication ratios. More prospective
randomized controlled studies are required in order to reveal the efficiency difference between
cryoablation and RFA. We consider that in order to decrease the complication rates and to increase
efficiency, making a good preoperative assessment and avoidance of RFA in central, renal tumors
larger than 4 cm will be a rationalist approach.
Keywords: Radiofrequency ablation; Kidney; Renal cell carcinoma; Complications
Introduction
Renal cell cancer is the most fatal urologic cancer [1] which is diagnosed at the metastatic
stage in 20-30% [2]. As a result of the improvements in USG, CT and MRI technologies in course
of time; incidental tumor determination ratio that was 10% in 1970s [3] has increased to 61% at
the end of 1990s [4]. Thus today, we encounter small-sized renal masses more frequently when
compared to the past. Generally small-sized renal masses are defined as slowly progressing masses
with a size of ≤4 cm and have a good prognosis [5]. The gold standard treatment for small-sized
renal masses is open/laparoscopic/robotic partial nephrectomy [6]. Minimal invasive therapies with
low complications rates can be applied to; elder comorbid patients or the patients with genetic
predisposition for multiple tumors or patients with bilateral tumors or patients with a solitary
kidney. Radiofrequency ablation, cryoablation, microwave ablation, stereotactic radiosurgery, laser
ablation and high-intensity focused US ablation take place among the minimal invasive treatment
approaches. Most of these methods are at experimental stage but cryoablation and RFA are intensely
used in clinical practice [6].
RFA is an ablation treatment that is approved by FDA (US Food and Drug Association)
regarding to the treatment of soft tissue tumors. It is used in the treatment of liver, lung and bone
tumors. In 1997, after Zlotta et al. [7] has firstly used RFA in the treatment of RCC, RFA has found
a wide clinical usage area in the treatment of small-sized renal masses. In this review, we want to
investigate the oncological efficiency and reliability of RFA in ablative treatment of small kidney
tumors with the current literature.
Technique and Mechanism of Action
Although RFA (Radiofrequency ablation) can be applied percutaneously and laparoscopically, current literature belongs mostly to the percutaneous technique. Percutaneous approach is generally applied under general anesthesia or sedation but general anesthesia is preferred in laparoscopic technique. The selection of technique depends on the operator and it seems that percutaneous or retroperitoneoscopic approach is more suitable for the treatment of lateral and posterior located cell damage occurs as a result of protein denaturation, membrane catabolism and cell vaporization. In the late period (after third day), fibrotic scar occurs as a result of the development of coagulation necrosis [13]. Temperatures over 105oC cause gas formation and this may disrupt RF current. Thus in RF ablation, the target is to keep the temperature on the tumor tissue between 50oC and 100o C [14]. Ablation should be targeted till 0.5-1 cm beyond the deepest point of the tumor, because in a report, live tumor cells are found periphery of the tumor in a patient to whom RFA is applied [15]. Besides conventional ablation, there are also researches about ablation via multiple electrodes. This system permits the usage of up to 3 electrodes, power varies between the electrodes respectively and thus a larger ablative zone is formed via thermal synergy [16]. System is new and although phase 2 studies are encouraging, the results should be supported via new studies [17]. It is recommended to apply CT/MRI imaging subsequent to RFA after 1-3 months, perform 3 scans in 6-month intervals and then 1 interval per year [18]. After the first scan (postoperative 1-3 months), contrast-enhancing lesions are accepted as insufficient ablation and re-application of RFA may be required. In the study of Gervais et al. [19] consisting of 100 patients, low tumor size (p < 0.0001) and non-central location (p = 0.0049) for complete necrosis after a single ablation are determined as independent predictor factors.
Oncologic and Overall Outcomes
There are numerous studies in the literature regarding to the
long-term oncologic efficiency of RFA application in small-sized
renal masses. Levinson et al. [20] have shared the long-term followup
results of RFA in small renal masses in 2008. In this study, in a
follow-up of mean 57.4 months, disease-specific, metastasis-free,
recurrence-free and general survival ratios are reported as %100,
%100, %79.9 and %58.3 respectively. In the same study, creatinine
value decrease is measured as 0.15 (p=0.06). In 2010, Ferakis et al. [21]
have published 61.2 months average follow-up results of CT-guided
percutaneous radiofrequency ablation in 39 renal tumors smaller
than 7.5 cm. while the first ablation success ratio is 90%, complete
ablation ratio after repeating the treatment has reached to 97%. In a
5-year follow-up; recurrence ratio is found as 10.4%. For recurrence,
various parameters are examined via multivariate analysis and the
tumor size over 4 cm is defined as a risk factor (P<0.01, relative risk
[RR] =3.31). Zagoria et al. [22] has determined recurrence in 5 of 48
RCC which percutaneous RFA is applied (12%). While median index
size is 5.2 cm in recurrent tumors (interquartile range [IQR]: 4-5.3),
median index size in the tumors with no local recurrence is observed
as 2.2 cm (IQR: 1.7-3.1, p=0.0014). In a study with median follow-up
of 54 months for RFA-applied 159 renal tumors; 3 and 5-year diseasefree
survival are observed as 92% and 91% respectively. In the same
study, local recurrence is directly found as related to size [23]. In
2012, Psutka et al. [24] have applied RFA to 143 T1a and 42 T1b RCC
and compared their oncologic results. When the results are inspected,
5-year survival as recurrence-free, metastasis-free survival, cancer
specific survival, disease-free survival and general survival ratios are
found worse in T1b RCC group when compared to T1a group. Lorber
et al. [25] have published the long-term results of percutaneous or
laparoscopic RFA-applied patients by using a real-time thermometer
with the aim of applying appropriate heat to 53 renal masses in
2014. In a mean follow-up period of 65.6 months; local recurrence
is observed in 4 (7.5%) patients and distant metastasis without local
recurrence is observed in 1 patient. 5-year overall survival of these
patients is informed as 98%, cancer-specific survival as 100% and
recurrence-free survival as 92.5%.
In a study comparing oncologic results of RFA and partial
nephrectomy which is having a follow-up period of more than 6 years;
despite RFA group’s comorbidities are more and they are older, the
survival ratios of the patients in RFA group are found similar to the
PN patients [26]. In this study, RFA vs. PN 5-year general survival,
cancer-specific survival, disease-free survival, local recurrence free
survival, metastasis free survival was found 97.2% vs. 100%(p=0.31),
97.2% vs. 100%(p=0.31), 89.2% vs. 89.2%(p=0.78), 91.7% vs.
94.6%(p=0.96), and 97.2% vs. 91.8%(p=0.35), respectively. In another
study, RFA and PN are compared in 90 T1a RCC patients and 5-year
oncologic results were found similar [27]. Besides intraoperative
blood loss is higher (p <0.001), operation period is longer (P <0.001)
and in the final follow-up, GFR value has decreased more (p=0.005)
in PN group. In terms of major complications (Clavien system ≥IIIa),
no difference is observed between two groups. While assessing the
results of this study, it should be considered that tumor sizes of PN
group are bigger. In the study of Faddegon et al. [28] published in
2013; RFA-applied 142 RCC patients and PN-applied 205 RCC
patients are compared in terms of renal functions and on the 5th year
and it is shown that 85.4% of RFA-applied patients and 82.1% of PNapplied
patients have continued their lives without Chronic Kidney
Disease stage progression, however this difference cannot reach to
a statistical significance level (p=0.06). In the study of Thompson
et al. [29] examining 1424 T1a RCC patients, PN is applied to 1057
patients, RFA is applied to 180 patients and cryoablation is applied to
187 patients. When the patient groups are compared, similar survival
ratios are observed among 3 groups without local recurrence (p=0.49)
however metastasis-free survival was found better in PN (p=0.005)
and cryoablation (p=0.021) groups when compared to RFA group.
Although general survival is found higher in PN group, it is suggested
that this finding has occurred due to the young age of PN patients
and their lower Charlson scores. In the study of Takaki et al. [30]
published in 2014, RFA and PN were compared in the treatment of
T1b renal tumors. On the 1st post-treatment month, GFR (Glomerular
Filtration Rate) reduction ratio is statistically significantly higher in
the PN group when compared to the RFA group (P=0.001). Besides
no significant difference is found between major (p= 0.61) and
minor (P = 0.12) complications between two groups. Despite general
survival ratios are better in PN group (p=0.009), higher age and ASA
(American Society of Anesthesiologists) scores of RFA group requires
a closer approach to this finding. In the same study, the disease-free
survival ratios are found similar in both groups (p=0.99). In the study
of Whitson et al. [31] in which they have examined ablation-applied
(cryoablation, RFA or NOS) or PN-applied 8818 T1a RCC patients
via the Surveillance Epidemiology and End Results (SEER) database,
it is found that RFA has twice increased RCC mortality risk when
compared to PN (hazard ratio 1.9, 95% confidence interval 1.1–3.3,
p=0.02). 5-year disease-free survival ratios are observed as 98.3% in
PN group and as 96.6% in ablation group. When the details of this
wide study are examined, it is seen that the number of RFA-applied
patients is 219 and 50% of these patients have no histologic data.
Thus these results should be carefully considered. Again in another
study performed by examining the SEER database data, regarding to
renal masses smaller than 7 cm, PN (n=4402), Radical nephrectomy
(n=10.165) and RFA/Cryoablation (n: 578) are compared and 1
and 2-year cancer-specific survival (CSS) are found as 99.4% and
98.0% for TA (termal ablation)group and as 99.6% and 99.3% for
PN group and as 98.9% and 98.0% for Radical nephrectomy group.
In univariate analysis, CSS is found significantly lower in TA group
when compared to PN group. (1.6% vs. 0.7%; P =0.025). However,
when the TA and PN patients are compared in terms of age, gender,
tumor size, race, geographic location, no difference is found. (hazard
ratio 0.6, 95% CI 0.28–1.28; P =0.2) [32]. In this study, no subgroup
analysis is done for the tumors smaller than 4 cm. In a meta-analysis
consisting of 6471 small-sized renal masses examining 99 studies of
Kunkle et al. [33] when compared to PN, higher local progression
ratios in cryoablation (RR = 7.45) and RFA (RR = 18.23) are observed.
However, no difference is observed between the groups in terms of
metastatic progression risk. In the meta-analysis of Katsanos et al.
[34] performed in 2014 by scanning the PubMed, EMBASE, AMED,
database, includes the studies with 6 or more stars on Newcastle-
Ottawa Scale, thermal ablation (RFA or microwave) was compared to
PN in small-sized renal masses in 587 patients. In this study, general
complication ratios were found lower in ablation group (7.4 vs. 11 %;
RR: 0.55, 95 % confidence interval [CI]: 0.31–0.97, p=0.04), besides
postoperative GFR reduction was found higher in nephrectomy group
(mean difference: -14.6 ml/min/1.73 m2, 95 % CI: -27.96 to -1.23, p
= 0.03). Local recurrence ratios (3.6 vs. 3.6 %; RR: 0.92, 95 % CI: 0.4–
2.14, p = 0.79) and disease-free survival ratios are found similar (HR:
1.04, 95 % CI: 0.48–2.24, p = 0.92) in both groups. As a result, when
the literature is examined, it is seen that radiofrequency ablation has
lower complication ratios than partial nephrectomy in the treatment
of renal tumors smaller than 4 cm and has a close-may be equaloncologic
efficiency with nephrectomy. Again while the literature
is being examined, it is observed that mostly the retrospective data
is examined and there are some problems regarding to the patient
selection (differences in age, comorbidity and tumor size between
the groups etc.). In order to obtain more exact conclusions, more
prospective randomized controlled studies are required.
In the small-size RCC treatment; the evidences regarding to the
efficiency of cryoablation increase every passing day like RFA. Due
to being a minimal invasive treatment and having low complication
and high efficiency, cryoablation continues its claim of being an
alternative for PN like RFA. Thus the number of studies comparing
the efficiency of both minimal invasive treatments increases day
by day. Cryoablation and RFA have some technical superiority
than each other. In central renal tumors, efficiency of RFA should
be elaborated. Gervais et al. [19] have shown that RFA has a local
recurrence increase in central renal tumors. Similarly, Gupta et al.
[35] have revealed that in central renal tumors treated by RFA, 4
times increased insufficient treatment risk is present when compared
to the non-central tumors. Takaki et al. [36] have shown that local
control in central tumors (67%) is lower than the non-central tumors
(96%). Besides cryoablation can be used safely and efficiently in
the treatment of central renal tumors [37]. During RFA procedure,
coagulation of puncture tract with probe change makes RFA attractive
in the patients with high bleeding risk, than cryoablation [38]. When
the studies comparing the efficiencies of RFA and cryoablation are
compared, various results can be observed in the literature.
In the study of Atwell et al. [39], cryoablation is applied for 189
renal tumors smaller than 3 cm and RFA is applied for 256 renal
tumors. 1, 3and 5-year recurrence-free survival are observed as 100%,
98.1%, and 98.1% in RFA group and as 97.3%, 90.6% and 90.6% in
cryoablation group however this difference can’t reach to statistical
significance (p=0.09). Major complications are found as 4.3% after
RFA and as 4.5% after cryoablation and no difference is observed
(p=0.91). The point to consider while assessing the results of this
study is that the tumors in cryoablation group are bigger than the
RFA group (p<0.001). In 2011, Pirasteh et al. [40] have compared
cryoablation and RFA in small-sized renal tumors in 111 patients.
In this study, local recurrence is observed as 11% in RFA group and
as 7% in cryoablation group and this difference has not reached to
statistical significance (p=0.60). In the first meta-analyses published
in 2008 comparing the efficiencies of cryoablation and RFA [33,41],
it is found that cryoablation is superior in the treatment of smallsized
renal tumors in terms of oncologic means when compared to
RFA. In the meta-analysis published by Kunkle and Uzzo [41], 1375
renal tumors treated via RFA or cryoablation are examined and local
tumor progression ratios are found higher than cryoablation (12.9%
vs. 5.2%; P< .0001). Although metastasis develops less in cryoablation
patients (1%) than the RFA (2.5%) patients, this difference cannot
reach to statistical significance (p=0.06). Also recurrent ablation
has occurred at a higher ratio in RFA group when compared to the
cryoablation group (8.5% vs. 1.3%; P< .0001). In the meta-analysis
of AUA (American Urological Association) performed in 2009 [42]
local recurrence-free survival ratios for RFA (85.6%) and cryoablation
(87.2%) are found similar and these are observed as lower than the
surgical methods (PN/Radical nephrectomy). While assessing these
findings, it should be considered that failure after the first ablation
was accepted as local recurrence in this study. However, it is known
that most of the patients can continue their lives as recurrence-free
with secondary ablation. Besides the success of ablation treatments
is only assessed by local recurrence in this study. Unlike these earlyperiod
meta-analyses, in the meta-analysis published by El Dib et al.
[43] in 2013, 457 cryoablation cases are compared to 426 RFA cases
and clinical efficiency is measured by using the below mentioned
parameters: cancer specific survival rate, radiographic success, no
evidence of local tumor progression or distant metastases. The pooled
proportion of clinical efficacy calculated as 89% in cryoablation group
and as 90% in RFA group. Besides no difference is observed between
cryoablation and RFA groups in terms of complications. Except all
this information, in the studies comparing RFA and cryoablation in
the literature until now, the minority of prospective/randomized data
and the suboptimal design of the studies (ex: ages of the patients and
the differences in the tumor sizes) draw attention. The data acquired
until now are far away from obtaining exact conclusions.
Although RFA is generally observed as safer than surgical
methods, when the current literature is examined in terms of
the complications of RFA, a wide clinical picture is encountered
(Hematuria, flank bruise, paresthesia and pain, perinephric
hematoma, ileus, urinary retention, urinoma, ureteral stricture,
tract abscess, hemorrhage, urinary fistula, neuropathic pain, atrial
fibrillation, pneumonia etc.) In order to avoid complications, it is
required to assess the surrounding tissues via imaging methods in
detail before RFA. Hemorrhagic complication rates after RFA are
similar to percutaneous renal biopsy and generally they are recovered
via conservative follow-up. Filling the tract with hemostatic agents
generally minimizes this complication [44]. In order to both
avoiding from hemorrhagic complications and preventing urinary
system injuries; avoidance from RFA in central tumors seems to be
a rationalist approach. In order to avoid an intestinal injury, which
is one of the most threatening complications, it is recommended to
use laparoscopic RFA application in the patients with no suitable
intestinal anatomy in preoperative prone CT [45]. Alternatively, for
safety purposes, saline, C02 or water can be applied adjacent to the
kidney in order to remove the intestine minimum 2 cm away from the
kidney before the operation [46].
Conclusion
RFA is a good alternative treatment method for the RCC’s smaller than 4 cm with an oncologic efficiency closer to nephron protecting surgery and with lower complication ratios. More prospective randomized controlled studies are required in order to reveal the efficiency difference between cryoablation and RFA. We consider that in order to decrease the complication rates and to increase efficiency, making a good preoperative assessment and avoidance of RFA in central, renal tumors larger than 4 cm will be a rationalist approach.
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