Comparing Oncologic Outcomes of Heat-Based Thermal Ablation and Cryoablation in Patients With T1a Renal Cell Carcinoma: A Population-Based Cohort Study From the SEER Database

According to the most recent guidelines [1, 2, 3], partial nephrectomy is the gold standard for treating patients with clinical T1a solid renal masses, with oncological results comparable to those of radical nephrectomy and better renal function preservation. However, owing to comorbidities, renal insufficiency, and advanced age, some patients require minimally invasive procedures. Thermal ablation (TA), in the form of heat-based TA (hTA) and cryoablation (CA), is an alternative strategy for older individuals and those with competing health risks. The American Urological Association recommends TA only for tumors no more than 3 cm in length [1]. The European Association of Urology guidelines state that, while TA is an option for all clinical T1a tumors, CA is preferred over hTA in patients with a tumor size of 3.1–4 cm [2]. The most general guidelines come from the National Comprehensive Cancer Network, which recommends all TA modalities as viable options for clinical T1a tumors of all sizes [3].

A recent study using the Surveillance, Epidemiology, and End Results (SEER) database explored an important dilemma regarding small renal mass management by investigating cancer outcomes following hTA or CA in patients with a tumor size of 3.1–4 cm [4]; however, certain limitations should still be considered. Local tumor excision is not only less traumatic but also not inferior to partial nephrectomy in terms of relapse or mortality [5]; thus, it may not be appropriate to merge CA and any type of local tumor excision for analysis [6]. Additionally, a meta-analysis comparing radiofrequency ablation (RFA, a type of hTA) with CA for T1 (T1a and T1b included) renal tumors demonstrated no differences in terms of the primary technique efficacy rate or 5-year survival rate [7]. Nevertheless, most of the included studies reported shorter follow-up periods. Moreover, in a retrospective study with 12 years of experience, high technical success and local disease control were achieved for microwave ablation (MWA, another kind of hTA) and CA, and the cancer-specific survival (CSS) was equivalent for clinical T1a (≤4 cm) renal masses [8]. However, the overall power of this study may be limited by the sample size. Therefore, to address the limitations of the current studies and provide a better clinical reference, we relied on the SEER database (2000–2019) to compare the efficacy of hTA and CA in treating patients with clinical T1a renal cell carcinoma.

TA is an important treatment option for patients with clinically diagnosed T1a renal masses. CA is one of the most studied ablation modalities for renal masses, and MWA, a newer option for hTA, has demonstrated high technical and clinical efficacies [10, 11]. Compared with RFA, MWA is considered to achieve more homogenous heating, higher tissue temperatures, and larger ablation volumes and is less affected by the heat sink effect [12]; thus, MWA is associated with a relatively lower local recurrence rate [13]. However, current guidelines concerning hTA are mostly based on studies on RFA [14, 15]. Although Sorce et al. [4] were the first to compare CA and hTA (including MWA) in patients with clinical T1a renal RCC with a tumor size of 3.1–4 cm [4, 16], they did not distinguish CA from CA combined with local tumor excision, which demonstrated superior oncologic outcomes to those of TA [6].

In our study, patient demographics and tumor characteristics were similar to those reported previously [4, 17]. There was no statistically significant difference between hTA and CA in cancer-specific outcomes not only in the entirety of the PSM cohort but also in the subgroups of patients with a tumor size ≤3 cm and those with a tumor size of 3.1–4 cm. As for OS, there was no significant difference between the two groups, only for patients with a tumor size ≤3 cm. A meta-analysis of single-arm studies conducted by Martin & Athreya [18] to compare MWA (7 studies) and CA (44 studies) in patients with small renal masses demonstrated a significantly larger tumor size in the MWA group and similar local tumor recurrence and CSS rates between treatments. According to Wu et al. [11], MWA demonstrated favorable short- to intermediate-term oncological outcomes (pooled 1-, 3-, and 5-year CSSs of 100%, 100%, and 97.7%, respectively; pooled 1-, 3-, and 5-year OS rates of 99.0%, 96.0%, and 88.1%, respectively), including the T1b subset (pooled 1-, 3-, and 5-year CSS rates of 98.2%, 97.2%, and 98.1%, respectively; pooled 1- and 3-year OS rates of 94.3% and 89.3%, respectively). A single-arm pooled meta-analysis suggested that compared with CA, MWA significantly improved the 1-year local tumor recurrence rate, and the 1- and 5-year OS estimates were 98% and 87%, respectively, for both modalities [19].

A meta-analysis by Choi et al. [20] revealed a local recurrence rate of 2.1% for MWA, which is slightly better than that reported in other studies for RFA (3.2%–13.0%) or CA (2.7%–8.7%) [21, 22, 23, 24, 25]. Thus, in the present study, the cancer-specific outcomes of hTA were comparable to those of CA. A possible explanation for the lower incidence of MWA recurrence can be found in the study by Bhardwaj et al. [26], who investigated the histological findings of ablations produced by MWA, RFA, and CA in rat livers. Although all procedures induced macroscopically distinct ablated lesions, microscopic analysis revealed significant differences. MWA showed the clearest zone of coagulative necrosis and a microscopically sharp demarcation zone between the ablated and unablated tissues, whereas with CA, hepatocyte survival toward the edge of the ablation was observed, especially when the vessels were close to the ablation margin. Furthermore, RFA sections showed the most irregular burn edges of the three ablative techniques, and, as with CA, islands of viable hepatocytes were found within the ablated tissue.

Contrary to previous studies [4, 27], our investigation revealed no statistically significant difference between hTA and CA in cancer-specific outcomes in patients with renal masses measuring 3.1–4 cm in size. Similarly, in a network meta-analysis of local recurrence and other oncologic outcomes after TA in T1b RCC, no differences were found between TA techniques [28]; however, the limited and variable follow-up between studies made it more difficult to pool the results. Thus, a larger cohort of patients with a tumor size of 3.1–4 cm and longer systematic imaging follow-up is necessary.

The novelty of our study is that hTA is comparable to CA in the treatment of clinical T1a renal masses, even those with a tumor size of 3.1–4 cm. However, several limitations should be considered when drawing these conclusions. First, this study was retrospective. Moreover, standardized specimen management, central pathology evaluation, data on complications, and early cancer control endpoints such as local recurrence or disease-free survival are lacking. Second, the only available information concerns the initial treatment. Subsequent treatments may have been used; however, they were not directly addressed in the current study. Third, the SEER database does not include data on tumor complexity (RENAL or PADUA score) or the number of kidney tumors. These factors are associated with varying degrees of morbidity and, as a result, may affect patient survival. Finally, the longtime span may have influenced ablation techniques, with a shift toward more minimally invasive and personalized patient approaches. Furthermore, better-quality prospective studies with protocol-driven inclusion and exclusion criteria, appropriate controls, standardized outcome measures, and adequate follow-up are needed to confirm our findings.

In conclusion, in patients with clinical T1a RCC, hTA was comparable to CA in terms of CSS and CSM, regardless of the tumor size. However, hTA resulted in a slightly shorter OS than did CA. Future large-scale and cross-regional randomized clinical trials are needed to validate our findings and the impact of different TA modalities on patient outcomes more precisely.

The Supplement is available with this article at https://doi.org/10.3348/kjr.2024.0462.

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