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Page 14 of 19 Deivasigamani et al. Mini-invasive Surg 2023;7:9 https://dx.doi.org/10.20517/2574-1225.2022.99

respectively. After combinatorial treatment, this increased the overall ablation volume from the ice ball and
tumor susceptibility to freezing by 32%. These in vitro findings imply that combination therapy may be a
viable therapeutic adjunct when using CA to treat RCC.

[96]
Liu et al. studied the efficacy of sorafenib alone compared to the therapy of sorafenib + PCA in 156
patients with advanced RCC who were not candidates for surgery. Objective response rate (ORR) and
disease control rate (DCR) were considerably higher in the combination therapy group, and progression-
free survival (PFS) and overall survival (OS) was also significantly longer in the combination group (both
P < 0.05). Immune function-related markers significantly improved after therapy in the CA + sorafenib
group (P < 0.05), while there was no significant change between before and after treatment in the sorafenib-
only group (P > 0.05).

Sunitinib
[97]
Cheng-Yuan Gu et al. compared the efficacy of sunitinib alone to combination therapy with sunitinib and
PCA in 178 patients with metastatic RCC. The combination therapy group who were treated with PCA and
sunitinib group had a superior PFS of 13.8 months vs. 7.2 months (P < 0.005) as well as a superior OS of 31.7
months compared to 19.8 months (P < 0.001). These findings suggest that chemotherapy plus CA may be
better than chemotherapy alone for select patients with metastatic RCC, but additional larger studies will be
needed to fully define the role of CA in this setting.

Tremelimumab
[98]
Campbell et al. conducted a pilot study to compare the efficacy of Tremelimumab (an anti-CTLA-4
agent) alone to combination therapy with Tremelimumab and CA in patients with metastatic RCC. This
pilot study was relatively small, with only 29 total patients, but they did not find a difference in treatment
discontinuation, PFS, or OS, but they did find that combination therapy with CA and tremelimumab
appeared to promote a greater immune cell response in patients with clear cell RCC.

Allogenic NK cell immunotherapy
[99]
Lin et al. studied CA alone compared to CA combined with allogenic NK cell immunotherapy in patients
with advanced RCC. The patients who underwent combination therapy with CA and allogenic NK cell
immunotherapy had a smaller post-ablation tumor size and a higher Karnofsky performance status, but
they did not have a sufficient sample size and follow-up to determine whether there was an effect on PFS or
OS.

Transarterial embolization
Pre-ablation transarterial embolization (TAE) of a renal tumor prior to CA has been reported in several
small series as a successful method for treatment for large tumors and central tumors [100,101] . Donato et al.
[102]
recently reported a series where TAE was employed prior to PCA for patients with cT1b or central cT1a
tumors. In this series, the authors reported that 19 patients underwent TAE prior to PCA, with one patient
having major complications and three patients with minor complications, all patients achieving technical
success, and one patient had local tumor recurrence at a median follow-up of 26 months. TAE followed by
PCA may be a useful strategy for surgery would present an unacceptably high risk but who have large renal
tumors or central renal tumors that would have a decreased chance of successful treatment with PCA alone;
however, more research will be needed to determine if this strategy is safer and/or more effective than PCA
alone for these patients.