Cryoablation of Kidney Tumors

Introduction

Cryoablation is used to destroy tumors in various organs, including the lungs, liver, prostate, and kidneys. In urology, this treatment method is considered a relatively new and reliable option for managing small renal tumors, although long-term follow-up data remain limited.

In recent years, advances in tissue and organ imaging technologies, including ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), have enabled the incidental detection of approximately 60% of small renal tumors measuring up to 4 cm [1].

Currently, small renal tumors account for approximately 70% of all diagnosed kidney tumors. When a renal tumor is detected at an early stage, minimally invasive treatment can be performed to remove or destroy the tumor while preserving the kidney [2].

Partial nephrectomy is the first-line treatment for renal cell carcinoma measuring up to 4–7 cm [3]. To reduce mortality associated with surgical treatment, renal tumor cryoablation is increasingly being used in patients with small kidney tumors.

Cryoablation typically involves two freeze–thaw cycles. During the freezing phase, the aim is to expose the renal tumor to a temperature of −40°C. This is followed by an active thawing phase, during which the temperature within the tumor reaches 6–8°C.

After the first cycle, a second freezing and active thawing cycle is performed.

Cryoablation induces renal tumor cell death through two mechanisms. The first involves direct damage to cell membranes and organelles, disrupting the movement of water and dissolved substances into and out of cells. The second involves indirect vascular injury, resulting in thrombosis of small blood vessels [4].

The cryoablation procedure is summarized in Table 1.

Methods

Renal tumor cryoablation can be performed using several approaches: percutaneous, laparoscopic, and open surgical techniques.

Laparoscopic cryoablation is performed under ultrasound guidance. The main advantage of this approach is easier access to anterior and renal hilar tumors. It also allows the surgeon to displace the colon and other adjacent organs to improve procedural safety [5].

Percutaneous cryoablation is more suitable for tumors located on the posterior and lateral surfaces of the kidney.

The advantages of percutaneous cryoablation include faster postoperative recovery, avoidance of general anesthesia, and the possibility of performing the procedure in a day-case setting [6].

Guidelines

The European Association of Urology guidelines state that, because of the lack of reliable clinical trial data, there is insufficient evidence to establish definitive recommendations regarding indications for renal tumor cryoablation [3].

In contrast, the American Urological Association guidelines identify ablative techniques, including renal tumor cryoablation, as third-line treatment options for patients with cT1a renal tumors who have severe comorbidities and an increased risk associated with surgical treatment [7].

To reduce surgery-related mortality, renal tumor cryoablation or radiofrequency ablation has been proposed for selected groups of patients.

According to these guidelines, cryoablation may be justified by the relative simplicity of the procedure, a lower likelihood of complications, and a shorter treatment duration [8].

Advanced age and severe comorbidities are relative contraindications to surgical treatment.

The mean age of patients undergoing percutaneous renal tumor cryoablation at the Mayo Clinic was 69.7 years, compared with 72.6 years among patients treated at Washington University Hospital [9].

Other potential indications for this treatment include having a solitary kidney, a transplanted kidney, or frequently recurrent renal disease [10].

Renal tumor cryoablation may also be considered in patients with von Hippel–Lindau disease, tuberous sclerosis, and other hereditary renal tumor syndromes.

These patients face an increased risk of developing renal failure because of repeated surgical procedures. Therefore, cryoablation may represent a first-line treatment option in such cases [11].

Relative contraindications to cryoablation include tumors larger than 4 cm, renal hilar tumors, intrarenal tumors, and cystic tumors.

Complication rates vary considerably depending on the characteristics of the patient population, tumor size and location, type of procedure, and the physician's experience.

According to published data, the overall complication rate ranges from 7.8% to 20% [12].

The most common complication is discomfort at the probe insertion site, reported in 64% of patients [13].

Severe complications, including injury to adjacent organs, damage to the renal collecting system, major bleeding, and fistula formation, are uncommon.

According to the literature, complication rates range from 0.8% to 9.5% for laparoscopic cryoablation and from 0% to 7.5% for percutaneous cryoablation [11].

Preservation of renal function is one of the primary objectives in the treatment of kidney tumors.

Cryoablation inevitably causes some damage to healthy renal tissue surrounding the tumor because complete tumor destruction requires the ablation zone to extend beyond the tumor margins. Consequently, a small amount of adjacent healthy tissue is also destroyed.

A study by Tsivian and colleagues demonstrated that renal function parameters remained unchanged or showed only minor changes after laparoscopic tumor cryoablation in patients with chronic renal insufficiency [14].

Haber and colleagues evaluated renal function in patients with a solitary kidney following laparoscopic nephrectomy and laparoscopic cryoablation.

The glomerular filtration rate decreased by 14.5% after laparoscopic nephrectomy and by 7.3% after cryoablation [15].

According to data from two of the largest meta-analyses, there were no statistically significant differences between laparoscopic and percutaneous cryoablation in terms of renal function preservation [6, 20].

The likelihood of local tumor recurrence is higher after cryoablation than after surgical resection.

Kunkle and colleagues found that the risk of local tumor recurrence following laparoscopic cryoablation was 7.45 times higher than after laparoscopic partial nephrectomy [16].

One of the largest meta-analyses compared treatment outcomes following laparoscopic cryoablation and surgical tumor removal.

In the cryoablation group, the local recurrence rate was 9.4%, while the rate of distant metastases was 4.4% [17].

Repeat cryoablation is commonly selected as a nephron-sparing procedure when local tumor recurrence occurs after an initial cryoablation.

The rate of repeat ablation is approximately 1% (0.9–1.3%) [18].

Assessing the long-term outcomes and complications of repeat cryoablation is difficult because of limited available data.

According to a study by Matin and colleagues, the local tumor recurrence rate after repeat cryoablation was 4.2% [19].

Treatment outcomes following laparoscopic and percutaneous cryoablation have also been compared.

According to Zagar and colleagues, five-year follow-up demonstrated no statistically significant differences in treatment outcomes between percutaneous and laparoscopic cryoablation [20].

Percutaneous cryoablation is associated with a higher likelihood of residual tumor but a lower probability of tumor recurrence [6].

Clinical Experience

Renal tumor cryoablation procedures are performed at the National Cancer Institute (NCI) in Lithuania. Cryoablation is used to treat patients with von Hippel–Lindau disease and patients with a solitary functioning kidney when the tumor is located in its central region, with the aim of preserving renal function for as long as possible.

Urologists at the NCI have experience treating patients with these types of renal tumors. Cryoablation has been performed in 26 patients, providing substantial clinical experience.

Particular attention is given to patients with von Hippel–Lindau disease. Two patients with this condition have been treated at the NCI. In both cases, multiple cryoablation procedures were performed under ultrasound and/or CT guidance because the natural course of the disease is associated with recurrent renal tumors.

In the first patient, six renal cell tumors were ablated. The patient was followed for 28 months. Renal function remained satisfactory, with a serum creatinine level of 108 µmol/L and a glomerular filtration rate of 68 mL/min/1.73 m².

In the second patient, five renal cell tumors were ablated. The patient was followed for 48 months. Renal function remained good, with a serum creatinine level of 67 µmol/L and a glomerular filtration rate of 123 mL/min/1.73 m².

Cryoablation is an alternative treatment option for patients with small renal tumors. Although there are no clearly defined criteria for selecting patients for this treatment, several factors should be considered, including tumor size and location, patient age, general health, renal functional capacity, and whether the patient has a solitary kidney. The patient's preferences are also important.

Because of the higher likelihood of local tumor recurrence and the risk of distant metastases, cryoablation is not recommended for young patients without comorbidities or with uncomplicated comorbid conditions.

Chang and colleagues state that, in healthier patients (65 years of age, whose tumor size…

Table 1. Overview of the Cryoablation Method

Advantages	Indications	Contraindications	Disadvantages
Minimally invasive procedure	Tumor size up to 4 cm	Young patients without severe comorbidities	Higher risk of local tumor recurrence than after surgical treatment
Can be performed in a day-case setting	Advanced patient age	Tumors larger than 4 cm	Damage to healthy tissue adjacent to the tumor caused by freezing
Shorter hospital stay	Complicated comorbidities	Renal cystic tumors	Lack of long-term follow-up data
Low complication rate	Solitary or transplanted kidney, or diagnosed renal insufficiency	Tumors located near other organs (e.g., the intestine)
Nephron-sparing treatment option for patients with renal insufficiency	Von Hippel–Lindau disease and hereditary, recurrent renal tumors

G. Andreikaitė¹, Aušvydas Patašius, MD², Albertas Ulys, PhD²

¹ Urology Center, Vilnius University Hospital Santaros Clinics

² Department of Oncourology, National Cancer Institute

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Internistas, Oncology Supplement, 2018.