Percutaneous Computed Tomography-Guided Cryoablation as a Treatment Option in Patients with Small Renal Masses: A 10 Year Experience in a Single Center

Simple Summary

The therapeutic approaches for patients with small renal tumors (T1) who are not candidates for surgery present a diverse array of options. Among these, cryoablation has long been regarded as one of the most effective percutaneous, minimally invasive techniques, offering comparable oncological efficacy and therapeutic radicality. Specifically, renal function both before and after cryoablation remains largely unaffected in this patient population. Through our case series, we aim to demonstrate that cryoablation is not only effective in terms of surgical radicality, but also a safe procedure with no associated toxicity, particularly ensuring that renal function is preserved.

Abstract

Background: To evaluate p-Cry in 10 years as a feasible and radical approach in patients with small renal masses (<5 cm), we evaluated technical success, side effects, and survival rates. Materials and Methods: We retrospectively evaluated 421 patients with small renal masses (<5 cm) with a median age of 70 years (47–92 C.I.) between June 2014 and July 2024 at our department. We also evaluated side effects, surgical radicality, and therapeutic outcomes of renal functions. Survivals were also evaluated in terms of disease-free, metastasis-free, and cancer-related survival rates. Results: Median follow-up was 90 months (1–120 months C.I.), and median size of the tumor was 3.85 cm (1–4 C.I.). Two cryoprobes were used in median, and two 10-min freeze–thaw cycles were performed. The technical efficacy rate was 100%, whereas only one of 121 lesions required retreatment. No impact on the renal function was registered after p-Cry. Cancer-free survival and metastases-free survival was reached. Conclusions: Compared to surgery, p-Cry is a feasible treatment option in patients with small renal masses, as it does not affect renal function and gives patients good survival rates.

1. Introduction

The removal of renal tumors has proven to be a safe and effective method for managing localized disease and preserving kidney function in patients with small renal cancers. Various retrospective studies have demonstrated positive outcomes for percutaneous cryoablation (p-Cry) of cT1a tumors, comparing favorably to partial nephrectomy (p-Ne) and radical nephrectomy (r-Ne). These studies have shown no significant differences in rates of local recurrence or metastasis-free survival (MFS) between the methods [1,2,3,4,5,6,7,8]. These findings prompted both the American Urological Association and the European Urological Association (EAU) to update their guidelines, recommending percutaneous cryoablation as a viable alternative to partial nephrectomy and active surveillance for treating cT1a solid renal masses smaller than 3 cm [9,10,11,12] in selected and frail patients. The most robust evidence supports the use of radiofrequency (RF) ablation and cryoablation (CA)—the two ablation techniques with the longest clinical history. Recently, p-Cry has gained prominence as an effective ablation option and has increasingly replaced partial nephrectomy in cases where surgery is not advisable, both in Europe and globally. The laparoscopic approach to p-Cry for small renal masses was first introduced by Gill and colleagues in 1998, offering a valuable treatment alternative for elderly or comorbid patients unsuited for surgery. p-Cry has the following advantages over partial nephrectomy: (a) it enables rapid and sustained freezing and thawing of the targeted tissue volume; (b) the gas used can permeate all tissue types without resistance; and (c) it is less vulnerable to thermal degradation. As we mentioned in our previous paper [13], p-Cry does not impair renal function and yields survival outcomes comparable to those of partial nephrectomy. Despite the number of papers highlighting the benefits of p-Cry in frail patients, there remains a gap in the literature concerning long-term survival and functional outcomes in a large cohort of patients.

The aim of this study is to evaluate side effects, surgical radicality, and therapeutic outcomes on renal function in a large cohort of patients that underwent p-Cry at our institution 10 years ago. Survivals were also evaluated in older patients with renal tumors ≤ 4 cm (cT1a), in terms of disease-free, metastasis-free, and cancer-related survival rates.

2. Materials and Methods

Following Institutional Board approval, we conducted a retrospective evaluation of 421 patients with small renal masses (under 4 cm) who underwent percutaneous cryoablation (p-Cry) at our department between June 2014 and July 2024. The median age of patients was 70 years (range of 47–92 years, with a 95% confidence interval). Patients were selected for p-Cry based on the following inclusion criteria: tumor diameter under 4 cm (classified as T1a); presence of comorbidities or contraindications to anesthesia that precluded partial nephrectomy (p-Ne); remaining renal masses after prior surgeries; or having only one functional kidney. Patients were excluded based on the following exclusion criteria: there was no viable percutaneous window for the procedure; involvement of renal veins or adjacent organs; renal masses larger than 4 cm, anesthetic contraindications; or if they declined the procedure.

Each patient was evaluated by a urologist prior to being referred to interventional radiology (IR), with assessments that included blood tests and laboratory evaluations to monitor renal function before and after treatment, as well as dual-phase abdominal CT scans for treatment planning. Additionally, all patients underwent CT-guided needle biopsy of the lesion using an 18-gauge needle, with an average of two cores per biopsy. Patient demographic data were collected from electronic medical records. Tumors were classified based on the RENAL nephrometry score, which considers parameters such as tumor radius, exophytic or endophytic nature, proximity to the collecting system or renal sinus, anterior or posterior position, and location relative to polar lines. This score was determined using preoperative magnetic resonance imaging (MRI) or computed tomography (CT) of the abdomen [14,15].

2.1. p-Cry

All cryoablations were performed by a dedicated interventional team consisting of a urologist and an interventional radiologist, using a GE Medical System BrightSpeed CT scanner. Patients were pre-treated with 2 g of cefazolin and 400 mg of ciprofloxacin to reduce infection risks. Patients were positioned in a prone position in order to optimize the surgical window. As noted previously, a pre-procedural non-contrast CT was conducted to evaluate the kidney mass location, size, and determine the number of probes required. If necessary, hydro-dissection was utilized to shield nearby organs from potential damage.

The surgical site was isolated and anesthetized locally with 15 mL of 200 mg lidocaine. Cryoprobes were then inserted directly into the renal mass through a small skin incision to create an “ice-ball” that extended approximately 5 mm beyond the tumor’s margins. The entire procedure was monitored via CT fluoroscopy. Argon and helium gases (Endocare, HealthTonics Inc., Austin, TX, USA) were used for the cryoablation, following a freeze–thaw cycle protocol. Each procedure employed cryoprobes with a 2.5 mm diameter.

Upon completion of the p-Cry, a contrast-enhanced CT scan was performed to confirm adequate tumor coverage and check for any bleeding. Patients were then transferred to a specialized recovery area for monitoring, with blood samples taken at 3 and 6 h post-procedure and again the following day before discharge. If no complications were observed, patients were discharged the day after the procedure following an overnight stay. Any complications were recorded and classified using the modified Clavien–Dindo classification system [16].

2.2. Follow-Up

Patients were followed up at 3, 6, 12, 18, 24, 36, and 48 months post-pCry, with annual visits continuing for a minimum of 5 years and up to 10 years. These follow-ups included blood tests and contrast-enhanced dual-phase CT imaging, conducted with a low-dose protocol to minimize radiation exposure. All CT scans were reviewed by the same interventional radiologist, who compared the images to the initial pre-pCry planning study. The success of pCry was assessed based on tumor enhancement and size across consecutive radiological follow-ups. A complete response was defined as the total absence of contrast enhancement in a previously enhanced mass. Conversely, local recurrence was identified if there was nodular enhancement within or near the ablation site following a previously documented successful treatment.

2.3. Statistical Analysis

The primary endpoints of our study included surgical efficacy, metastasis-free survival (MFS), disease-free survival (DFS), progression-free survival (PFS), and renal function assessment post-pCry. Cancer-specific survival was defined as the percentage of patients who did not die from progression of the ablated tumor. Overall survival (OS) was defined as the time from pCry to death or as the percentage of patients alive at a 10-year follow-up. Metastasis-free survival (MFS) represented the percentage of patients alive without metastatic lesions following pCry, while disease-free survival (DFS) indicated the percentage of patients alive without disease recurrence after the procedure. Kaplan–Meier survival curves were employed to evaluate DFS, MFS, and OS.

Continuous variables were reported as means, standard deviations, medians, and interquartile ranges, and were analyzed using descriptive statistics. Categorical variables were presented as rates. A p-value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using Stata software version 18 2023 (StataCorp LP, College Station, TX, USA).

3. Results

Patient demographics and cancer characteristics are summarized in

Table 1. Patient characteristics.

Variables	Value
Age, years, median (IQR)	70 (47–92)
Sex, male	275
Sex, female	146
Biopsy result, RCC	461 (100%)
Clear cell	277 (60%)
Chromophobe	184 (40%)
Number of cryoprobes, median (IQR)	2 (1–4)
Tumor diameter	3.85 (1–4)

. The study included 461 renal lesions across 421 patients, of whom 275 were male and 146 were female, all presenting with small renal masses (<4 cm). The median patient age was 70 years (range of 47–92 years, CI), with procedures conducted between June 2014 and July 2024 at our department. The median lesion size was 3.85 cm (range of 1–4 cm, CI). All patients underwent biopsy confirmation before pCry, with clear renal cell carcinoma being the most common histological type (277 out of 461 lesions, 60%), followed by chromophobe renal cell carcinoma (184 out of 461, 40%).

The median number of cryoprobes used per procedure was directly proportional to lesion size (p < 0.02), with an average of 2 probes (IQR 1–3) according to lesion size, and a median of 2 freeze–thaw cycles of 10 min each in 400 lesions; for the remaining 61 lesions, 3 cycles of 5 min each were applied. No cases of damage to adjacent organs were recorded, and no patients developed ablation-related infections, such as renal abscesses or sepsis, demonstrating the procedure’s safety. Median hospitalization time was 2 days (IQR 1–4).

The technical success rate of pCry was 100%, with all 461 lesions successfully ablated. Primary technical effectiveness reached 99.5%, as only 1 of 461 cryoablated lesions required re-treatment due to residual tumor presence. Minor adverse events included four cases of asymptomatic perirenal effusion, which resolved spontaneously, and five cases of mild back pain managed with simple analgesics. Recurrence was observed in only one lesion, corresponding to a recurrence rate of 0.6% (1 out of 461). Median follow up was 90 months (1–120 months C.I.). Cancer specific survival was 98% in terms of DFS, 97% in terms of MFS, and 100% in terms of OS, as shown by graphics in Figure 1 and Figure 2. Despite their comorbidities, all 421 patients are alive at the follow-up visits conducted by us, the interventional radiologists, as well as at the appointments with our oncology and urology colleagues. Therefore, the overall survival data were obtained by cross-referencing information on patients’ health status from our follow-up assessments and those carried out by our urology and oncology colleagues, who monitor these patients more closely. After p-Cry, the diameters of lesions continued to reduce over time. The relative reduction in the lesion size compared to pre-p-Cry values was 22% at 12 months fup, 35% at 36 months fup, and 60% at 48 months fup. The apparent diameter increase in the lesions after p-Cry is linked to post-procedural edema of the surrounding tissues. Concerning kidney functions, all serum creatinine levels after p-Cry remain overlapped with pre-p-Cry values, suggesting that p-Cry did not affect renal function. To assess that, we performed a paired t-test for pre- and post-ablation creatinine serum levels of each patient, with a p value = 0.125, demonstrating the lack of influence of p-Cry on renal function

4. Discussion

The present study aims to demonstrate both functional and oncological outcomes of percutaneous cryoablation (p-Cry) in a cohort of patients with small renal cancers, with a median age of 70 years (ranging from 47 to 92 years). The follow-up period extended over 10 years at a single center, providing long-term insights into both the safety and efficacy of the treatment. Oncological outcomes were promising, showing high disease-free survival (DFS) rates of 98%, overall survival (OS) rates of 100%, and metastatic-free survival (MFS) rates of 97%, with only minor complications directly related to the p-Cry treatment. These results align with those from other studies on cryoablation in small renal masses, confirming its effectiveness and minimal complication profile [17].

Patients diagnosed with small renal cancers have a range of treatment options, each of which comes with its own advantages and limitations. These options include surgery, such as partial nephrectomy, various ablative techniques like radiofrequency (RFA), and cryoablation (p-Cry), and, in some carefully selected cases, active surveillance. In the current era of precision medicine and treatment tailoring, clinicians face the challenge of selecting the best treatment approach that balances several factors: minimizing cancer-specific mortality, achieving high oncological radicality, preserving renal function, reducing treatment-related complications, and ensuring a good quality of life for patients. While numerous ablative approaches are available for small renal tumors, p-Cry is often favored due to its favorable outcomes and low complication rate, as reported in various studies. This has led p-Cry to become a standard of care in the treatment of small renal masses [18].

One of the major advantages of p-Cry is its relatively low impact on renal function. Cryoablation’s ability to preserve renal parenchyma is particularly important because the preservation of renal function is directly related to post-procedural kidney filtration. The literature demonstrates that p-Cry results in less renal parenchymal volume loss compared to surgical resection [19]. This is especially beneficial for patients with comorbidities, such as elderly patients with impaired glomerular filtration rates (GFRs) [20,21,22,23,24,25].

In this context, several studies have suggested that p-Cry is superior in preserving renal function, particularly when compared to other treatment options (microwaves, radiofrequences, or partial nephrectomy), which can lead to significant renal parenchymal loss. Our study supports these findings, as we observed no significant decline in renal function during the follow-up period (with p = 0.125 at a paired t-test, as previously reported).

This result aligns with the work of others, such as that of Larcher et al., who reported stable renal function following cryoablation in elderly patients [26].

In terms of oncological outcomes, our study demonstrated an overall survival (OS) rate of 100%, a metastatic-free survival (MFS) rate of 97%, and a disease-free survival (DFS) rate of 98%.

For instance, Shingleton et al. [16] reported similar 5- and 10-year DFS rates following cryoablation in a cohort of patients with small renal tumors. Additionally, other studies have shown that p-Cry offers excellent cancer control with low rates of recurrence, making it a viable alternative to surgery. The excellent survival outcomes reported in our study are consistent with these observations, highlighting p-Cry’s role in achieving long-term cancer control [27,28,29].

Despite the promising results, it is important to note that many studies mentioned in the vast literature have explored the role of p-Cry in treating small renal tumors; however, most of these studies lack long-term follow-up data. The few studies that do include long-term follow-up support the notion that p-Cry is effective over time; although, more evidence is needed to conclusively define its role in the management of small renal masses [30]. The long-term outcomes provided in our study add valuable insight into the sustained efficacy and safety of this treatment modality, further emphasizing the need for further large-scale, long-term prospective trials.

In conclusion, despite the many ablative therapies available for small renal tumors, p-Cry stands out as one of the safest options, with a relatively low incidence of complications. As highlighted in the literature, it offers an effective and minimally invasive alternative to more aggressive treatments such as surgery, with the added benefit of renal function preservation and excellent oncological outcomes [31]. Our study provides further evidence supporting its continued use as a standard treatment for patients with small renal masses, particularly in elderly patients or those with significant comorbidities who may not tolerate more invasive procedures.

However, this study has several limitations. First, it is retrospective in nature, which inherently introduces biases. Retrospective studies are often limited by data availability and potential for selection bias, and future prospective randomized trials are necessary to confirm these findings. Second, there was no control group comparing p-Cry to other treatment options, such as active surveillance or partial nephrectomy. The comparison of these modalities in a well-designed randomized controlled trial could provide more definitive guidance. We are actively working to collect more data and plan to publish a comparative study in the future. Third, the study relied on radiological imaging to monitor potential relapses rather than histological confirmation, which limits the definitive diagnosis of relapse in some cases. While imaging is a commonly used method for follow-ups, the lack of histological confirmation is a limitation that future studies may address by integrating biopsy or surgical intervention when recurrence is suspected [32].

5. Conclusions

Among our large cohort of patients, percutaneous cryoablation (p-Cry) has proven to be a highly feasible and effective treatment option for individuals with small renal masses, particularly those who are unfit for surgery due to age, comorbidities, or other health-related factors. One of the most significant benefits observed in our study is that p-Cry does not adversely affect renal function, which is a critical consideration in the treatment of renal tumors, especially for elderly patients or those with pre-existing renal impairments. The preservation of renal function is paramount, as it impacts the patient’s long-term quality of life and reduces the risk of developing chronic kidney disease or end-stage renal failure.

Moreover, the oncological outcomes observed in our cohort were highly encouraging, with the majority of patients demonstrating excellent survival rates. Specifically, the 10-year follow-up revealed an overall survival rate of 100%, a metastatic-free survival rate of 97%, and a disease-free survival rate of 98%, which are in line with or even superior to those reported in other studies that have examined p-Cry for small renal masses (Larcher et al., 2020; Gervais et al., 2015). These outcomes further underscore the effectiveness of p-Cry in controlling cancer, preventing metastasis, and ensuring long-term survival.

In addition to these promising survival rates, the incidence of complications associated with p-Cry was minimal, with only minor issues related to the procedure itself, such as transient post-procedural pain or minor hematomas. This low complication rate is consistent with other reports in the literature, which highlight p-Cry as a safe and well-tolerated treatment for patients who may not be candidates for more invasive surgical procedures (Gupta et al., 2017; Shingleton et al., 2018).

However, despite these positive outcomes, the next logical step in advancing our understanding of p-Cry is to compare it directly to partial nephrectomy, a treatment modality that remains the gold standard for patients with small renal tumors who are medically fit for surgery. Partial nephrectomy offers the advantage of direct tumor resection with the potential for a more radical oncological outcome, but it also carries a higher risk of complications, particularly in patients with comorbidities. Thus, comparing the outcomes of p-Cry with partial nephrectomy in a controlled study will provide valuable insights into which approach offers the best balance of cancer control, renal function preservation, and overall safety. This is the next challenge we are eager to address, and we are currently working to collect data for such a comparison.

The findings from this study contribute to the growing body of evidence supporting the role of p-Cry as a viable treatment option for small renal masses, particularly in patients who are not ideal candidates for surgery. As we continue to explore and refine our approach, we are optimistic that p-Cry will remain an essential tool in the management of small renal tumors, offering patients a less invasive option with excellent long-term outcomes.