Journal of
Clinical Medicine
Article
Image-Guided Ablations in Patients with Recurrent Renal
Cell Carcinoma
Gaetano Aurilio 1,† , Giovanni Mauri 2,† , Duccio Rossi 2, * , Paolo Della Vigna 2 , Guido Bonomo 2 ,
Gianluca Maria Varano 2 , Daniele Maiettini 2 , Maria Cossu Rocca 3 , Elena Verri 3 , Daniela Cullurà 3 ,
Franco Nolé 3 and Franco Orsi 2
Citation: Aurilio, G.; Mauri, G.;
Rossi, D.; Della Vigna, P.; Bonomo, G.;
Varano, G.M.; Maiettini, D.; Rocca,
M.C.; Verri, E.; Cullurà, D.; et al.
Image-Guided Ablations in Patients
with Recurrent Renal Cell Carcinoma.
J. Clin. Med. 2023, 12, 4902. https://
doi.org/10.3390/jcm12154902
Academic Editor: Harald Mischak
Received: 29 May 2023
Revised: 22 July 2023
Accepted: 24 July 2023
Published: 26 July 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
J. Clin. Med. 2023, 12, 4902. https://doi.org/10.3390/jcm12154902
1 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia IEO,
European Institute of Oncology IRCCS, 20122 Milan, Italy; gaetano.aurilio@ieo.it
2 Division of Interventional Radiology, Istituto Europeo di Oncologia IEO,
European Institute of Oncology IRCCS, 20122 Milan, Italy; giovanni.mauri@ieo.it (G.M.);
paolo.dellavigna@ieo.it (P.D.V.); guido.bonomo@ieo.it (G.B.); gianluca.varano@ieo.it (G.M.V.);
daniele.maiettini@ieo.it (D.M.); franco.orsi@ieo.it (F.O.)
3 Department of Oncology, Istituto Europeo di Oncologia IEO, European Institute of Oncology IRCCS,
20122 Milan, Italy; maria.cossurocca@ieo.it (M.C.R.); elena.verri@ieo.it (E.V.); daniela.cullura@ieo.it (D.C.);
franco.nole@ieo.it (F.N.)
* Correspondence: ducciorossi89@gmail.com
† Those authors contributed equally to this work.
Abstract: Renal cell carcinoma (RCC) is one of the most frequently diagnosed tumors and a leading
cause of death. The high risk of local recurrence and distant metastases represent a significant
clinical issue. Different image-guided ablation techniques can be applied for their treatment as an
alternative to surgery, radiotherapy or systemic treatments. A retrospective analysis was conducted
at our institution, including a total number of 34 RCC patients and 44 recurrent RCC tumors in
different locations (kidney, lung, adrenal gland, liver, pancreas, pararenal and other) using microwave
ablation, radiofrequency ablation, cryoablation and laser ablation. The estimated time to local and
distant tumor progression after treatment were 22.53 ± 5.61 months and 24.23 ± 4.47 months,
respectively. Systemic treatment was initiated in 10/34 (29%) treated patients with a mean time-to-
systemic-therapy of 40.92 ± 23.98 months. Primary technical success was achieved in all cases and
patients while the primary efficacy rate was achieved in 43/44 (98%) cases and 33/34 (97%) patients,
respectively, with a secondary technical success and efficacy rate of 100%. At a mean follow-up
of 57.52 months ± 27.86 months, local tumor progression occurred in 3/44 (7%) cases and distant
progression in 25/34 (74%) patients. No significant complications occurred. Image-guided ablations
can play a role in helping to better control recurrent disease, avoiding or delaying the administration
of systemic therapies and their significant adverse effects.
Keywords: renal cell carcinoma; ablation; metastasis
1. Introduction
Renal cell carcinoma (RCC) represents one of the most commonly diagnosed tumors
in men and women, accounting for about 2–3% of all adult malignancies worldwide [1].
RCC incidence has risen in recent decades mainly because of the increased use of imaging
techniques and it is expected to further increase, especially in developing countries, through
2030 [2]. According to the American Cancer Society estimates, the 5-year survival rate for
localized forms of RCCs is 93%, which decreases to 71% when regional lymph nodes or
surrounding tissues and organs are involved, finally reaching a dismal 14% when distant
metastases occur [3]. Currently, in the management of RCC patients, an image-guided
ablation therapy is increasingly offered as an alternative when surgery is not an option
because of comorbidities, as well as advanced age, metastatic disease or surgery refusal.
Along this line, a wide spectrum of local treatments, such as microwave ablation (MWA),
https://www.mdpi.com/journal/jcm
J. Clin. Med. 2023, 12, 4902 2 of 13

radiofrequency ablation (RFA), cryoablation (CA), high intensity focused ultrasound (HIFU)
and laser ablation, can play an important role throughout all stages of RCC treatment.
Because of this, a multidisciplinary approach to recurrent RCC (rRCC) patients, including
image-guided ablation treatments, has become increasingly required, aiming to provide a
safe and effective treatment strategy. In particular, image-guided ablations can be useful in
the multimodal approach to oligometastatic or oligoprogressive patients in order to avoid
or delay the start of systemic treatments and their toxicity profiles. The aim of the present
study is to report the results of the application of image-guided ablations in the treatment
of patients with rRCCs, particularly focusing on the possibility of avoiding or delaying
systemic treatments in those patients.

2. Materials and Methods

A retrospective analysis of electronic records and imaging databases was undertaken
to identify patients who underwent the image-guided ablation of rRCCs. Institutional
review board approval was obtained and patients’ informed consent was waived.
Indication to image-guided ablation was taken into a multidisciplinary meeting in-
volving urologists, radiologists, oncologists and radiation therapists. The percutaneous
approach was chosen taking into account age, comorbidities, tumor location, size and its
proximity to critical non-target structures. The ablation technology adopted depended on
various factors such as preference and familiarity of the first operator, morphological char-
acteristics and location of the tumor, intraprocedural morphological results and technology
availability. All procedures were performed by different interventional radiologists, at least
one of these with more than 10 years of experience.

2.1. Procedures
All ablation procedures were performed in one of two dedicated angio suites. One
room was equipped with a C-arm (Ziehm Vision RFD Hybrid Edition, Ziehm Vision,
Nuremberg, Germany), a computed tomography (CT) (GE Lightspeed, GE Healthcare,
Chicago, IL, USA) and an ultrasound (US) machine (GE E9, GE Healthcare, Chicago, IL,
USA) equipped with a dedicated fusion imaging software. The other room was equipped
with a hybrid angiography CT solution (ALPHENIX 4D CT, Canon Medical Systems
Corporation, Kanagawa, Japan) and a US machine (GE E9, GE Healthcare, Chicago, IL,
USA) equipped with dedicated fusion imaging software. All procedures were performed
under general anesthesia. Careful patient positioning planning was performed and the
most advantageous decubitus was secured with the help of dedicated devices such as a
vacuum mattress to immobilize the patient body during the procedure. A contrast enhanced
CT (CECT) scan was then performed to evaluate the tumor and allow for fusion imaging
with US images. On the basis of the size and geometry of the tumor and its relationships
with adjacent organs, the best access strategy was decided. Adjunct procedures to displace
sensitive structures, such as hydrodissection, were applied according to interventional
radiologist’s judgment. The ablative devices were than inserted under real time US/CT
fusion imaging guidance, and correct device position was confirmed with a CT scan.
Regarding RF, a LeVeen 17 G umbrella-shaped electrode (LeVeen CoAcces RFA, Boston
Scientific, Marlborough, MA, USA, needle electrode) was adopted using increasing power
up to roll-off twice. Regarding MW, a 13 G internally cooled antenna (Emprint, Medtronic,
Minneapolis, MN, USA) was used. Power and time were established according to the
manufacturer indications and to the size and shape of the tumor to be treated on a case-
by-case basis. Regarding laser ablation, under CT-US fusion imaging, a 21 g needle was
inserted at the level of the lesion to be treated and its correct position confirmed by an
unenhanced CT. Then, a 0.3 mm laser fiber was introduced into the 21 g needle and
thermal ablation was performed with a commercially available semi-conductor diode laser
system with a wavelength of 1064 nm (Echolaser, Elesta Srl., Florence, Italy). A fixed
3 W power protocol was used with a total energy delivered of 1200–1800 J for a single
illumination. Cryoablation was performed using the ProSense system (Ice-Cure Medical
J. Clin. Med. 2023, 12, 4902 3 of 13

Ltd., Caesarea, Israel). Two to three cycles of freezing with intervening passive thaw
were applied according to manufacturer indications and the lesions’ size. After ablation,
independently from the adopted technique, a CECT was always performed to control for
the immediate result and eventual presence of complications. In the case of a suspicious
persistence of pathological tissue beyond the ablation area, device repositioning and a
further ablation were performed in the same manner as previously described. For all
treatments, a CECT within 24 h was performed to evaluate early treatment outcomes and
complications. Finally, if no complications were observed, the patient was discharged the
day after.

2.2. Follow-Up Protocol

Follow-ups were performed by CECT or contrast-enhanced MRI at established in-
tervals (6 weeks, 3, 6, 12 months) following the first treatment and subsequently on an
annual basis by the same group of interventional radiologists who routinely take care of
these patients.

2.3. Variables and Data Analysis

Technique feasibility was defined as the possibility to perform the ablation. In the
case of any factor (e.g., the impossibility to perform general anesthesia, or to achieve a
safe distance from critical structures with hydrodissection), the procedure was considered
unfeasible. Technical success was considered as the tumor being treated according to the
pre-established protocol and covered completely by the ablation zone, while technique
efficacy was defined as complete ablation at 6 months from treatment. Primary efficacy rate
was defined as the percentage of complete ablation following the initial treatment, whereas
secondary efficacy rate was considered as the percentage to complete ablation, including
eventually repeated ablations. The time to first recurrence was defined as the time from
primary surgery to first recurrence. Tumor progression was evaluated as local (recurrence
at the site of ablation) or distant (development of new metastases), and the time to local and
distant tumor progression (local-TTP, distant-TTP) were estimated with the Kaplan–Meier
method. Time to systemic therapy initiation was evaluated, accounting for the time from the
first ablation to the time of first systemic therapy prescription. The overall survival (OS) and
disease-free survival (DFS) were estimated with the Kaplan–Meier method. Complications
were recorded and classified in minor, major and severe adverse events (AEs) according
to the Society of Interventional Radiology classification [4,5]. Statistical analyses were
performed using commercial software package XLSTAT (Addinsoft, New York, NY, USA).
Results were reported as means, standard deviation (SD), medians and ranges for the
quantitative variables and percentages for the categorical variables.

3. Results
Between January 2012 and October 2021, a total number of 34 patients (mean patients
age 64.5 ± 10.4, 10 F, 24 M) underwent the treatment of 44 metachronous tumors (mean
number of tumors per patient: 1.29 ± 0.40; median: 1; range 1–2) in 35 treatments. A
histological diagnosis of both the primary renal tumors and recurrent tumors were available
for all patients that underwent image-guided ablation. All patients were oligometastatic,
with 24/34 (71%) accounting for one lesion site and 10/34 (29%) for two lesion sites. The 44
treated lesions included mostly the contralateral kidney (n = 23/44; 52%), lung (n = 5/44;
11%), adrenal glands (n = 4/44; 9%), liver (n = 3/44; 7%), pancreas (n = 1/44; 2%) and
five soft-tissue sites: pararenal space (n = 3/44; 7%), perisplenic space (n = 2/44; 5%),
retroperitoneal space (n = 1/44; 2%), abdominal wall (n = 1/44; 2%) and subdiaphragmatic
space (n = 1/44; 2%). Regarding the histologic subtypes of treated patients, the absolute
majority of them were RCCs (33/34; 97%) with 32/33 (97%) accounting for clear cell RCCs
and 1/33 (3%) patients for type 1 papillary tumors.
J. Clin. Med. 2023, 12, 4902 4 of 13

Tumor grade was determined using the Fuhrman grading system with the majority
of treated lesions (31/44; 71%) accounting for Grade 2 and 3. The clinicopathological
characteristics of treated patients are summarized in Table 1.

Table 1. Characteristics of 34 patients who underwent image-guided ablation of rRCC (n = 44) in 35

treatment sessions.

Characteristic Value
Mean Age (y) 64.5 ± SD 10.4
Sex
- M 24/34 (71%)
- F 10/34 (29%)
Treated tumors’ location
- Kidney 23/44 (52%)
- Lung 5/44 (11%)
- Adrenal gland 4/44 (9%)
- Liver 3/44 (7%)
- Pancreas 1/44 (2%)
- Pararenal 3/44 (7%)
- Perisplenic 2/44 (5%)
- Retroperitoneal 1/44 (2%)
- Abdominal wall 1/44 (2%)
- Subdiaphragmatic 1/44 (2%)
Per-patient’s lesions
1 lesion site 24/34 (71%)
2 lesion sites 10/34 (29%)
Histologic subtype
- RCC 33/34 (97%)
- Clear cells- Papillary (type 1) 32/33 (97%)1/33 (3%)
- Not-defined RCC 1/34 (3%)
Fuhrman grading scheme
- Grade 1 1/44 (2%)
- Grade 2 21/44 (48%)
- Grade 3 10/44 (23%)
- Grade 4 2/44 (5%)
- Not available 10/44 (23%)
Adopted ablation techniques
MWA 26/35 (74%)
RFA 5/35 (14%)
MWA + RFA 1/35 (3%)
Laser 2/35 (6%)
Cryoablation 1/35 (3%)
Image-guided ablations were feasible in all cases. The median time to first recurrence following treatment for
primary RCC was 36 months (range, 0–167 months).

At a mean follow-up time of 57.52 ± 27.86 months (median 59.80; range, 8.67–99.47 months),
local tumor progression (LTP) was identified in 3/44 (7%) lesions that were successfully
retreated with percutaneous ablation.
The estimated mean time to local-TTP was 22.53 ± 5.61 months (Figure 1).
Regarding patients’ overall progression, 25/34 (74%) of the successfully treated patients
showed further disease progression with a mean time to distant-TTP of 24.23 ± 4.47 months
(Figure 2).
d. 2023, 12, x FOR PEER REVIEW 5 of 13

. 2023, 12,J.xClin.
FORMed.
PEER REVIEW
2023, 12, 4902 5 of 13 5 of 13

Figure 1. Time to local tumor progression (TTP), per-lesion analysis (n = 44). Yellow dots = cen-
sored data.

Regarding patients’ overall progression, 25/34 (74%) of the successfully treated pa-
Figure 1. Time to local1.tumor progression (TTP), per-lesion analysis (n =analysis
44). Yellow dotsYellow
= cen- dots = cen-
tients showedFigure
further disease
Time progression
to local with a mean
tumor progression (TTP), time to distant-TTP
per-lesion (n = of
44).24.23 ± 4.47
sored data.
months (Figure 2).
sored data.

Regarding patients’ overall progression, 25/34 (74%) of the successfully treated pa-
tients showed further disease progression with a mean time to distant-TTP of 24.23 ± 4.47
months (Figure 2).

Figure 2. Time to distant tumor progression (TTP), per-patient analysis (n = 34). Yellow dots = cen-
Figure 2. Time to distant tumor progression (TTP), per-patient analysis (n = 34). Yellow dots = cen-
sored data.
sored data.

Systemic treatment
Systemicwas initiated
treatment wasininitiated
10/34 (29%) treated
in 10/34 (29%) patients, with awith
treated patients, mean time-
a mean time-to-
Figure 2. Time to distant tumor progression (TTP), per-patient analysis (n = 34). Yellow dots = cen-
to-systemic-therapy of 40.92 ±of23.98
systemic-therapy 40.92months.
± 23.98 months.
sored data.
A flow chart of the course
A flow chart ofof 34course
the patients and
of 34 44 rRCC
patients lesions
and 44 rRCCislesions
available in Figure
is available 3.
in Figure 3.

Systemic treatment was initiated in 10/34 (29%) treated patients, with a mean time-
to-systemic-therapy of 40.92 ± 23.98 months.
A flow chart of the course of 34 patients and 44 rRCC lesions is available in Figure 3.
Med. 2023, 12, x FOR
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Med. 2023,REVIEW
12, 4902 6 of 13 6 of 13
J. Clin. Med. 2023, 12, x FOR PEER REVIEW 6 of 13

Figure 3. Flow chart of the course of 34 patients and 44 lesions from rRCC reporting treatment to
Figure 3. Flow chart of the course of 34 patients and 44 lesions from rRCC reporting treatment
last follow-up. PtsFigure 3. Ls
patient; Flow chartLTP
lesions; of the course
local tumorofprogression,
34 patients DM
and distant
44 lesions from rRCC
metastasis, reporting treatment to
TA tumor
tolast
last follow-up.
follow-up. PtsPts patient;
patient; Ls lesions;
Ls lesions; LTPLTP
locallocal
tumortumor progression,
progression, DM distant
DM distant metastasis,
metastasis, TA
TA tumor
ablation.
ablation.
tumor ablation.
As reported in Figure 4, the mean DFS was 33.08 ± 4.75 months.
As
Asreported
reportedininFigure
Figure4,4,the
themean
meanDFS
DFSwas 33.08±± 4.75
was33.08 4.75 months.
months.

Figure 4. Disease-free survival (DFS) of the whole cohort. Yellow dots = censored data.
Figure4.4.Disease-free
Figure Disease-freesurvival
survival(DFS)
(DFS)ofofthe
thewhole
wholecohort.
cohort.Yellow
Yellowdots
dots==censored
censoreddata.
data.

As shown in Figure 5, the mean OS was 57.52 ± 4.77 months.

2023, 12, x FOR PEER REVIEW 7 of 13

J. Clin. Med. 2023, 12, 4902 7 of 13

As shown in Figure 5, the mean OS was 57.52 ± 4.77 months.

Figure 5. OverallFigure
survival of the whole cohort. Yellow dots = censored data.
5. Overall survival of the whole cohort. Yellow dots = censored data.

Primary technical success

Primary was achieved
technical success wasin all lesionsinand
achieved all patients while
lesions and primary
patients whileef-primary
ficacy rate was achieved in 43/44 (98%) lesions and 33/34 (97%) patients due to a residual
efficacy rate was achieved in 43/44 (98%) lesions and 33/34 (97%) patients due to a residual
unablated tumor at first imaging follow-up. In this case, a second treatment was success-
unablated tumor at first imaging follow-up. In this case, a second treatment was successfully
fully performed performed and, therefore,
and, therefore, secondary
secondary technicalsuccess
technical success and
andefficacy
efficacy raterate
werewere
achieved in
all initially included lesions (44/44; 100%) and patients (34/34; 100%).
achieved in all initially included lesions (44/44; 100%) and patients (34/34; 100%).
A total amount of nine complications occurred over 44 treated lesions (20%) in
A total amount of nine complications occurred over 44 treated lesions (20%) in 5/34
5/34 (15%) patients. No minor complications (A–B) occurred. Major complications (C–F)
(15%) patients.accounted
No minor forcomplications
9/9 (100%) treated (A–B) occurred.
lesions. Major
No severe complicationsAEs
treatment-related (C–F)
(E–F)ac-
occurred.
counted for 9/9Complications
(100%) treated are lesions.
listed in NoTablesevere
2. treatment-related AEs (E–F) occurred.
Complications are listed in Table 2.
Table 2. Complications among patients (n = 34) who underwent image-guided ablation of rRCC
Table 2. Complications
(n = 44),among patients
classified (n =to34)
according SIRwho underwent image-guided ablation of rRCC (n
standards.
= 44), classified according to SIR standards.
Type of
Grading Number (%) Details
Grading Number (%) Type of complication Details
Complication

A A
No minor complications
B No minor complications
B 7-day
9/44(20%) 1/9 (11%) Pancreatic fistula
9/44 D hospitalization
1/9 (11%) Pancreatic fistula 7-day hospitalization
D (20%) 8/9 (88%)
Perilesional 3–5 days
hematoma hospitalization
8/9 (88%) Perilesional hematoma 3–5 days hospitalization

Images from a patient treated with MWA for a retroperitoneal recurrence are shown
Images from a patient treated with MWA for a retroperitoneal recurrence are shown
in Figure 6.
in Figure 6.
J. Clin. Med.
J. Clin. 2023,12,
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x FOR PEER REVIEW 8 of8 of
13 13

Figure 6. A 52-year-old patient with a right-sided retroperitoneal recurrence 2 years after a right-
Figure A 52-year-old
kidney6.partial patient
nephrectomy, withwith
treated a right-sided
MWA. (A)retroperitoneal
A PET-CT scanrecurrence
performed2ayears afterbefore
few days a right-
treatment
kidney showing
partial a right retroperitoneal
nephrectomy, nodule(A)
treated with MWA. with
A vivid
PET-CTFDG uptake.
scan (B) Non-enhanced
performed CT
a few days before
performedshowing
treatment during the procedure
a right showing hydrodissection
retroperitoneal performed
nodule with vivid with saline
FDG uptake. (B) solution to createCT
Non-enhanced
a safety margin
performed during(arrowhead) between
the procedure the tumor
showing (arrow) and
hydrodissection the adjacent
performed colon.
with saline(C) Non-enhanced
solution to create a
CT performed during the procedure illustrating the microwave antenna at the lesion
safety margin (arrowhead) between the tumor (arrow) and the adjacent colon. (C) Non-enhancedlevel (arrow).
(D–F) Contrast-enhanced CT performed at 24 h, 1.5 months and 1 year showing complete ablation
CT performed during the procedure illustrating the microwave antenna at the lesion level (arrow).
of the nodule (arrow) without contrast enhancement and no complications.
(D–F) Contrast-enhanced CT performed at 24 h, 1.5 months and 1 year showing complete ablation of
the nodule (arrow) without contrast enhancement and no complications.
4. Discussion
Approximately 20–30% of RCC patients have metastatic disease at diagnosis (syn-
4. Discussion
chronus disease), while
Approximately aboutof20–40%
20–30% of caseshave
RCC patients can develop distant
metastatic metastases
disease after the
at diagnosis (syn-
chronus disease), while about 20–40% of cases can develop distant metastases exhibit
initial diagnosis (metachronous disease) [6]. Of interest, 57 to 65% of RCC patients after the
singlediagnosis
initial sites of metastatic lesions,disease)
(metachronous being the number
[6]. of metastatic
Of interest, 57 to 65% sites
of inversely
RCC patients related to
exhibit
the patients’ age [7]. Recent estimates suggest that around 25% of RCC
single sites of metastatic lesions, being the number of metastatic sites inversely related patients with met-
achronous
to metastatic
the patients’ age [7].disease
Recentcould be candidates
estimates suggest that for local treatments
around 25% of RCC[8], and the most
patients with
metachronous metastatic disease could be candidates for local treatments [8], and(45.2%),
common metastatic sites to which we have to pay attention deal with the lung the most
bone (29.5%),
common lymphsites
metastatic nodes (21.8%),
to which weliver
have(20.3%), adrenal (8.9%)
to pay attention and brain
deal with districts
the lung (8.1%)
(45.2%), bone
[9,10].
(29.5%), lymph nodes (21.8%), liver (20.3%), adrenal (8.9%) and brain districts (8.1%) [9,10].
In the
In the last
last decade,
decade, many
many novel
novel therapeutic
therapeuticoptions
optionscombining
combiningmultikinase
multikinase inhibitors
inhibitors
and immune checkpoint inhibitors [11] have been investigated
and immune checkpoint inhibitors [11] have been investigated in metastatic RCC in metastatic RCC (mRCC)
(mRCC)
patients. Unfortunately,
patients. Unfortunately, the the variability
variabilityof oftrial
trialdesigns
designsand anddifferent
differentdrug
drugcombinations
combinations
have made
have made difficult
difficult to to establish
establish aa unique
unique first-line
first-linetreatment
treatment[12].
[12].Within
Withinthis thisscenario,
scenario,
conservative or
conservative or radical
radical surgery
surgery still
still persist
persistas asthe
thestandard
standardofofcarecarefor
forthe
thetreatment
treatment ofof
patients with localized or locally advanced RCCs [13,14]. Particularly, in
patients with localized or locally advanced RCCs [13,14]. Particularly, in isolated retroperi-isolated retroper-
itoneal recurrences after nephrectomy, a careful surgical resection is still supported [15],
toneal recurrences after nephrectomy, a careful surgical resection is still supported [15], but
but when a further oligometastatic progression appears, image-guided ablations can play
when a further oligometastatic progression appears, image-guided ablations can play a role,
a role, deferring the need for a systemic treatment [16–18]. The current literature suggests
deferring the need for a systemic treatment [16–18]. The current literature suggests that
that a locoregional recurrence after radical primary surgery most often behaves as a sys-
a locoregional recurrence after radical primary surgery most often behaves as a systemic
temic disease, with a lot of patients presenting distant metastases, while only a few of
disease, with a lot of patients presenting distant metastases, while only a few of them
them have exclusive locoregional recurrence. The latter is the ideal condition for image-
have exclusive locoregional recurrence. The latter is the ideal condition for image-guided
guided ablations [18,19].
ablations [18,19].
Image-guided ablations, such as MWA, RFA, MWA plus RFA, CA and laser ablation
Image-guided ablations, such as MWA, RFA, MWA plus RFA, CA and laser ablation
have significantly progressed over the past years and they represent a useful toolbox for
have significantly progressed over the past years and they represent a useful toolbox for
a multimodal approach to this disease [15,20–24]. The most common shared indications
a multimodal approach to this disease [15,20–24]. The most common shared indications
concern localized or small RCCs, unable to undertake surgery due to comorbidities, bilateral
tumors or locoregional recurrences.
J. Clin. Med. 2023, 12, 4902 9 of 13

Our data present a unique perspective of exclusive image-guided ablations applied to

the treatment of rRCC patients without including other local treatments such as stereotactic
radiosurgery (SRS), conventional radiotherapy (CRT) or stereotactic body radiotherapy
(SBRT). Our series included an heterogenous group of oligo-metastatic metachronous rRCC
patients with different tumor locations encompassing the contralateral kidney, lung, adrenal
gland, liver, pancreas and pararenal lesions.
Regarding the adoption of different ablation techniques, both RFA and CA are advised
by current guidelines for the treatment of RCC and are considered equivalent in terms of
excellent technical success rates and low tumor recurrence rates, even in cases of repeated
treatments [25–27]. Moreover, no significant outcome differences between the two tech-
niques regarding complications, metastasis-free rates and cancer-specific survival have been
reported [25,26,28]. Regarding MWA, due to its more recent development compared to RFA
and CA, limited studies, lacking in mid- and long-term follow-ups, are currently available.
However, MWA presents practical advantages compared to RFA, with shorter procedural
times and a reduced heat-sink effect, and also providing larger ablation zones [29–31]. In
our institution, due to a larger experience with MWA in different organs and locations,
we usually adopt this technique when technically feasible also for RCC lesions, without
observing a higher recurrence rate vs. other ablation techniques [22,32–34].
These technologies have been subsequently extended to the treatment of recurrent
and metastatic lesions even if the current literature is still limited. A study from Bang
et al. comprising a group of 27 patients (67% with intermediate risk) treated with cryoab-
lation for 72 tumors in heterogeneous locations, reported a median OS of 32.3 months vs.
57.52 months in our series. Also, even if the recurrence rate was reduced (1% vs. 7%), 22%
of patients received a systemic therapy before the ablation treatment [35]. Another paper by
Welch et al., involving 82 RCC heterogeneous lesions in 61 patients treated with different
image-guided ablation techniques, reported a technical failure in 4.9% of treatments with a
comparable recurrence rate (7.9% vs. 7% in our series) and a good 3-year OS of 76%. How-
ever, also in this case, 26% and 4% of patients received systemic therapy or radiotherapy
before ablation, respectively [36].
In our series, the treatments were feasible in all cases and locations with high technical
success and efficacy rates, supporting the role of image-guided ablations as flexible, safe and
effective treatment options for these patients. Moreover, at the same time no perioperative
systemic therapy was added as in other papers dealing with surgical treatments of RCC
local recurrences [37].
The quite-long median time to recurrence from the initial surgery in our series
(36 months; range, 0–167 months) gives a rationale to maintain such patients under follow-
up after the first initial nephrectomy, in order to identify those who could benefit from early
image-guided ablations [37–39]. Therefore, we also applied a strict follow-up after image-
guided ablation, identifying at a mean imaging follow-up time of 57.52 ± 27.86 months
(median 59.80; range, 8.67–99.47 months) an LTP in 3/44 (7%) of successfully treated tumor
lesions. Then, the estimated mean local-TTP was 22.53 ± 5.61 months, which is compa-
rable to recently published papers that included surgical resection as local treatment as
well [9,18,40]. Our results are in line with a surgical series from Ray et al. of 30 patients who
underwent resection for 26 local and regional RCC recurrences, showing a secondary recur-
rence in 53.8% of patients with a median time to recurrence of 11.5 months (range 7–29) [18].
Moreover, in a recent systemic review regarding surgical metastasectomy of metastatic
RCCs in various organs, a significant longer median OS or cancer-specific survival (median
40.8 months) was reported after complete metastasectomy compared with incomplete or
no metastasectomy, highlighting the role of local treatments in terms of survival outcome
improvement and the delaying of systemic treatment with its associated toxicity [9]. As de-
scribed in the surgical literature, estimates reports that 25% of patients with metachronous
metastasis might be candidates for local treatment [8]; however, patient selection can be
complex because of the heterogeneous course of RCC, surgical resectability and anatomical
access. According to this, establishing a role for other types of local therapies for rRCCs,
J. Clin. Med. 2023, 12, 4902 10 of 13

especially image-guided ablations, is of timely importance [41,42]. After image-guided

ablation, our data showed that progression at distance occurred in 25/34 (74%) patients at
a mean estimated time of 24.23 ± 4.47 months. Systemic treatment was started in 10/34
(29%) of our patients, at a mean time of 40.92 ± 23.98 months after the ablation. Therefore,
the start of a systemic therapy could be avoided in the large majority of cases, and when
required it could be postponed for more than three years, indicating an indolent course
of a patients’ disease after image-guided ablations. Moreover, systemic therapies, mainly
consisting of kinase inhibitors such as cabozantinib or sunitinib, and more recently im-
munotherapy such as nivolumab or pembrolizumab, are burdened by significant adverse
effects, most frequently of advanced grade, with a possible long-term impact on daily
patients’ quality of life [43–47]. It is worth mentioning that the complication rate involved
20% of all treated lesions, a finding that is lower than comparable locoregional surgical
treatments and systemic therapies [9,48].
In our series of rRCC patients, the mean OS was 57.52 ± 4.77 months, which was
comparable to different data reported in the review of Dabestani et al., in which many
studies on treatments of advanced RCC patients included metastasectomy and radiotherapy
modalities [9].
Overall, we believe that image-guided ablation can play a role as a less invasive
treatment in rRCCs, especially in metachronous oligo-metastatic patients with a low-to-
intermediate Fuhrman grade and long time to the first recurrence [49], accounting for low
complication rates, low morbidity risk with repeated procedures [50] and a prominent role
in delaying systemic treatments with their associated toxicity.
Finally, our study has some limitations, including the retrospective study design, the
small sample size and its heterogeneity with different metastatic locations and multiple
ablation methods adopted, which could not allow a per-location and per-treatment analysis.
Further studies with larger groups and longer follow ups are needed in the future to estab-
lish the ideal location site and ablation technique for these recurrences. Notwithstanding,
to date, no prospective trials regarding image-guided ablations for rRCC patients have
been performed and, to the best of our knowledge, this is currently one of the largest series
of rRCC treated with image-guided ablation. From this, our results can be considered
useful for generating hypotheses and planning further studies to shed light on the role of
image-guided ablations in the treatment of rRCC patients.

5. Conclusions
Over the last years, the therapeutic options for the treatment of mRCC patients have
significantly changed, especially with the introduction of immune-combination strategies
that became the standard of care in this disease setting, extending patients’ survival at
expenses of significant adverse effects.
Therefore, establishing a role for image-guided ablations that can help to better control
the disease and avoid or delay the administration of systemic therapies in carefully selected
rRCC patients is of paramount importance.

Author Contributions: Conceptualization, G.M. and D.R.; methodology, G.M. and D.R.; formal
analysis, G.M., G.A. and D.R.; investigation, G.M. and D.R.; data curation, D.R.; writing—original
draft preparation, D.R.; writing—review and editing, D.R., G.A., G.M., G.B., P.D.V., D.M., G.M.V.,
M.C.R., E.V., D.C., F.N. and F.O.; supervision, G.M., G.A., F.N. and F.O. All authors have read and
agreed to the published version of the manuscript.
Funding: This work was partially supported by the Italian Ministry of Health with Ricerca Corrente
and 5 × 1000 funds for the IEO European Institute of Oncology IRCCS.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Institutional Review Board of the IEO European Institute of
Oncology IRCCS (protocol code 2382).
Informed Consent Statement: Due to the retrospective nature of this study, specific informed consent
was waived.
J. Clin. Med. 2023, 12, 4902 11 of 13

Data Availability Statement: The data that support the findings of this study are available on request
from the corresponding author.
Conflicts of Interest: The authors declare no conflict of interest related to the present work.

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