## 4 Discussion
These studies encompassed a total of 74 RFA treated patients, with reported median OS values ranging from 6.0 to 24.03 months. The major heterogeneity in study design, patient population, and RFA protocols--combined with the lack of reported confidence intervals--precluded us from performing a formal meta-analysis employing standard statistical methods. However, we calculated a simple sample-size weighted average of the median OS across these four studies, with a pooled median OS of 12.7 months. There are several important limitations when interpreting this pooled median OS. First, it is based on data without matched controls, thus preventing direct comparison to other treatments. Second, patients varied in disease burden, from primarily locally advanced tumors in some studies to metastatic disease in others. Finally, none of the included studies reported a consistent set of covariates, such as performance status or prior chemotherapy, that could influence OS. Regarding PFS, only one study in our analysis reported a numerical median PFS [32] for PDAC patients undergoing EUS-RFA. Therefore, pooling data on progression-free survival was not possible. Future prospective trials should systematically report both OS and PFS with confidence intervals to allow for more rigorous meta-analyses. The ability to employ real-time imaging during EUS-RFA, offering the opportunity to precisely target the tumor, most likely contributes to the high success rate of this method [6; 7; 26]. Moreover, applying RFA through EUS also provides the opportunity to implement other therapeutic measures, such as celiac plexus ablation, in the same session, as reported by [PERSON] et al. [36]. Different approaches in terms of power settings, RFA electrode types, and the number of RFA sessions did not show a significant influence on the technical feasibility of the treatment [29; 31; 32]. This consistent technical success rate throughout the studies underpins the feasibility of the procedure, even in the challenging clinical settings of locally advanced or metastatic PDAC [29; 32; 33]. Another important aspect that needs to be addressed with every new therapeutic option is safety. Similar to the technical success rate, the overall safety profile of EUS-RFA was consistently favorable, with most adverse events being mild (transient abdominal pain or hyperamylasemia). Differences in study definitions and reporting criteria likely contributed to heterogeneity (I\({}^{2}\) = 52.4%). However, the pooled adverse event rate of 22.6% suggests that careful patient selection and periprocedural monitoring are essential for the timely diagnosis and management of these complications [20; 33; 34]. Severe complications, such as bleeding or duodenal structures, were rare but should not be overlooked [26; 29; 32]. The relatively low incidence of major adverse events supports EUS-RFA as a relatively safe alternative for patients with limited options, even though long-term safety, particularly in combination with systemic therapies, remains to be further explored [32; 34; 36]. Although technical success and safety are crucial, the ultimate measure of a treatment modality is represented by clinical efficacy. Tumor response variables, such as reductions in tumor size and serum markers such as CA 19-9, showed encouraging results in several studies [30; 31; 32]. However, the limited availability of consistent data on overall survival (OS) and progression-free survival (PFS) highlights a major knowledge gap in the current literature. While one study reported a median PFS of 16.37 months, this outcome was not consistently evaluated across other trials [32]. The absence of standard outcome measures limits the ability to draw definitive conclusions about the long-term efficacy of EUS-RFA for PDAC patients compared to that of the current standard of care [20; 29].