Research status and trend of lung cancer ablation therapy: a bibliometric analysis from 2002 to 2025

Introduction

Lung cancer remains one of the most prevalent and deadly cancers nowadays, with nearly 70% of patients not eligible for surgical treatment at diagnosis, making surgery rarely a treatment option (1). In patients with non-small cell lung cancer (NSCLC) who are ineligible for surgery, ablation therapy and radiotherapy have shown efficacy as a kind of local treatment (2,3).

Ablation therapy refers to the process of inducing tumor degeneration and necrosis through physical energy changes to eradicate tumor cells and alleviate associated symptoms. Currently, common physical ablation techniques include radiofrequency ablation (RFA), cryoablation, microwave ablation (MWA), as well as relatively rare ablation methods like high-intensity ultrasound, laser, and pulsed electrical field ablation (PEF). Some of those techniques have been successfully applied to treat other cancers, such as liver and kidney tumors, with good clinical results (4). In recent years, lung cancer ablation therapy has received increasing attention due to its efficacy, minimally invasive operation, and cost-effectiveness, and is being increasingly applied in clinical practice. There are thousands of related studies in this field from 2002 to 2025, covering some important areas like the treatment of both early-stage and advanced lung cancer, as well as the application of various ablation techniques. In order to systematically summarize significant previous studies and explore future research hotspots and trends, we conduct this extensive bibliometric analysis.

Bibliometrics is a quantitative research approach that employs statistical analysis of indicators such as publication citations, author collaborations, and journal impact factors (IFs). This method enables researchers to quickly evaluate the current research landscape and identify emerging hotspots and future trends. It outperforms reviews or meta-analyses in assessing the entire discipline with hundreds of publications (5). Currently, no bibliometric studies are exploring the connection between ablation therapy and lung cancer research. We conduct a quantitative bibliometric analysis of ablation therapy for lung cancer to provide a scientific foundation for critical issues and future research. We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2172/rc).

Methods

Study selection

The data source utilized in this study is the Web of Science Core Collection (http://wcs.webofknowledge.com). A thorough database search was conducted by Q.Z. and X.H. on July 7, 2025. The detailed search query is as follows: (I) TS = (“ultrasound ablation”) OR (“High intensity focal ultrasound”) OR (“HIFU”) OR (“cryoablation”) OR (“Cryosurgery”) OR (“Microwave ablation”) OR (“thermal ablation”) OR (“Radiofrequency ablation”) OR (“Radio-Frequency ablation”) OR (“Laser Ablation”) OR (“lung Ablation”) OR (“Pulsed Electric* Field”) OR (“Irreversible electroporation”). (II) TS= (((lung OR pulmonary) NEAR/0 (cancer OR carcinoma OR neoplasm OR adenocarcinoma OR nodule*)) OR (NSCLC) OR (SCLC) OR (“ground glass opacit*”) OR (“ground glass nodule*”)). (III) #I AND #II.

After the initial search, two authors (Q.Z. and Z.Z.) independently assessed the retrieved publications based on the following inclusion criteria: (I) the publication period is defined from January 1, 2002, to July 1, 2025; (II) only publications in English are considered; (III) the publication type is restricted to articles; and (IV) the study focus on lung ablation therapy. If there are any disagreements regarding the screened articles, another author (X.H.) should evaluate whether the article needs to be included in this study. The detailed screening criteria are illustrated in Figure 1. The final analysis includes a total of 919 publications, which are then exported in “plain text” format with “complete records and references”.

Figure 1 Flowchart of literature search selection.

Keyword analysis is crucial for research hotspots. To ensure consistency, we examined all keywords in the literature and further merge synonymous keyword [as follows: non-small-cell lung cancer and NSCLC merge into NSCLC; ground-glass opacity/opacities, ground-glass nodules (GGNs) merge into GGN; radiofrequency, radio-frequency ablation and RFA merge into RFA; microwave and MWA merge into MWA; Laser therapy and laser treatment merge into laser ablation; focused ultrasound and ultrasonic treatment merge into ultrasound ablation; thermal treatment merge into thermal ablation; programmed cell death protein 1 (PD-1) inhibitors merge into immune checkpoint inhibitors (ICIs); irreversible electroporation and irreversible electrical breakdown merge into PEF].

Data analysis

We use Excel software (2021) for table creation and descriptive statistical analysis. VOSviewer (version 1.6.20.0) is used to analyze and visualize co-occurrence and collaboration relationships among authors, institutions, and countries. CiteSpace (version 6.2.R1) is used to analyze the strongest citation bursts and create time-line views of keywords, presenting the evolution of research trends and recent research hotspots. The R software (v4.5.0) is used to visualize the changes in the number of publications of the top 10 journals and ablation types over the years, while the online analysis tool ‘Bibliometrix’ (v4.0.0) is used to analyze the topic trends related to author keywords.

Results

Documents

A total of 919 publications were retrieved in this field between January 1, 2002 and July 1, 2025. From 2002 to 2018, the annual publication volume increased gradually. From 2019 to 2025, the publication volume significantly increased, peaking in 2024 with 92 articles. By July 1, 2025, 55 articles had already been published (Figure 2). Notably, we find that China’s publication trend in recent years has largely aligned with the global trend. Since 2017, China’s annual publications have accounted for more than half of the global annual output, indicating rapid advancements in China’s research on lung cancer ablation.

Figure 2 Trends in publication output on ablation therapy for lung cancer form China and the world.

Authors

A total of 4,489 scholars participated in research on lung cancer ablation therapy, collectively publishing 919 papers. Table 1 lists the publication counts, country, institutions, H-index, and total citations of the top 12 core authors. Regarding publication volume, Ye Xin is the leading author with 64 papers, followed by Wei Zhigang with 54. Among the top 12, there are 8 Chinese scholars, 3 Japanese scholars, and 1 American scholar. Dupuy, Damian E., ranks first with 1,436 citations, followed by Japanese scholars Gobara, Hideo, and Kanazawa, Susumu (1,156 citations). Dupuy, Damian E., owns the highest H-index (H-index: 52), indicating his influence on lung ablation research. We use VOSviewer software to create a collaborative network map of scholars (Figure 3A). Statistical analysis set the minimum publication threshold at 5 papers, with 118 scholars meeting the criteria. The network map reveals the breadth of researcher collaboration and the concentration among certain collaborators. Node size in the visualization is proportional to the scholar’s publication count, with larger nodes indicating higher output. Figure 3B shows the annual publication trends of the top 10 authors, and Chinese scholars have continuously released publications in this field since 2014.

Figure 3 The analysis of cooperation and production of authors. (A) The cooperation of authors in ablation therapy and lung cancer; (B) the top 10 authors’ production over years. TC, total citation.

Institutions

A total of 1,103 institutions have published articles in lung cancer ablation (Table 2). Among the top 10 institutions with the publication output, six are from China. Shandong University leads with the most papers published [57] and 1,035 citations, followed by Shandong First Medical University with 46 publications and 465 citations. There are three U.S. institutions and one Japanese institution, with Okayama University having the highest output (32 papers) and 1,150 citations. Notably, Brown University, despite publishing only 28 papers, has the highest citations (1,814), demonstrating its strong influence in this field.

An analysis of institutional collaboration was conducted by VOSviewer software to create a network map of institutional partnerships (Figure 4). We set the number of publications threshold of 8, and 42 institutions surpass this criterion. It shows strong academic collaborations within both individual countries and internationally. The map underscores the significant role of institutions in the United States, China, and Japan.

Figure 4 Institutional collaboration in lung cancer and ablation therapy.

Countries

A total of 46 countries published articles, with the top 10 countries by publication volume listed in Table 3. China produces the largest number of publications, totaling 406 articles. The United States ranks second with 225 articles. The publication counts of other countries do not exceed 100. The United Kingdom has the highest average citations per article (60.9), indicating higher research quality in this field. The United States records the highest total citations (9,949) and the largest number of internationally collaborative articles [41], highlighting its substantial international research partnerships. Figure 5 shows the collaboration network among countries, with a minimum publication threshold of 5 articles. Twenty-one countries met this criterion. In the visualization, node size signifies a country’s publication volume, with larger nodes representing higher output. The figure demonstrates extensive collaborative relationships among countries.

Figure 5 National cooperation network graph in lung cancer and ablation therapy.

Journals

A total of 269 journals published literature on lung cancer ablation therapy. Table 4 provides a quantitative overview of the publication output and academic impact of each journal. Journal of Vascular and Interventional Radiology leads with 80 documents, with the highest citations (2,389) and link strength (1,077), demonstrating its high productivity and significant influence. Followed by the International Journal of Hyperthermia with 40 publications and 499 citations. Radiology, despite having fewer publications [16], stands out with 2,081 citations and an IF of 15.2, demonstrating its significant academic influence.

The bubble chart (Figure 6) illustrates the publication trends of the top 10 academic journals between 2002 and 2025, showing their annual document publication and trend. Overall, the Journal of Vascular and Interventional Radiology has maintained a consistently high level of article publication, with a steady increase since 2010. Other journals like Journal of Cancer Research and Therapeutics, thoracic cancer, and the International Journal of Hyperthermia have experienced a significant growth after 2015, reflecting the dynamic evolution of this research field. High-impact journals like The American Journal of Roentgenology and European Radiology intermittently publish relevant literature during this period.

Figure 6 The publications of the top 10 journals in lung cancer and ablation therapy by years.

Ablation type

This study included six different ablation therapies for lung cancer. The bubble chart is plotted based on author keywords, illustrating that RFA has consistently been a research focus. MWA has gained increasing attention and become a mainstream ablation therapy recently. Cryoablation has gradually gained acceptance as a main ablation therapy in recent years. Interest in laser ablation and PEF for lung cancer has also emerged, indicating a growing pursuit of multimodal approaches to lung cancer ablation therapy. Publications on ultrasound ablation for lung cancer treatment are limited (Figure 7).

Figure 7 Annual trends in published articles of different ablation topics.

Keywords

A total of 2260 keywords. The table presents the top 10 keywords related to lung tumors and ablation therapy (Table 5). The most frequently occurring keyword is “radiofrequency ablation” (417 occurrences, 2,341 total link strength), followed by “microwave ablation” (264 occurrences, 1,540 total link strength) and “thermal ablation” (226 occurrences, 1,506 total link strength).

The topic trend graph provides a more direct observation of the changes in thematic keywords over the years (Figure 8A). Particular attention should be given to recent trends, including the emergence of key terms such as radiomics, immune response, machine learning, and electromagnetic navigation bronchoscopy. It indicates the integration of ablation therapy for lung tumors with emerging research hotspots, driving advancements in the field.

Figure 8 The analysis of keywords in lung cancer and ablation therapy. (A) Topic trend graph by years; (B) top 25 keywords with the strongest citation bursts from 2002 to 2025; (C) the clustered network timeline view of author keywords.

Figure 8B illustrates the strongest keyword bursts of 25 keywords in the field of lung tumor and ablation therapy between 2002 and 2025. Keywords with strength greater than 10 include “follow-up” and “tissue ablation”. Initially, ablation techniques were primarily applied to treat lung malignancies, mainly used for the treatment of lung metastases. In recent years, focus has shifted toward treatment of high-risk pulmonary nodules, with attention to ablation therapy transitioning from RFA to MWA and cryoablation. Keyword clustering in Figure 8C was conducted using CiteSpace software. The time slice ranged from January 2002 to June 2025, with a 1-year interval per slice. The calculation method used was “LLR”. Other parameters are default settings. The Q-value of 0.4578 (>0.3) indicates a robust clustering structure, while the S-value of 0.7487 (>0.7) supports the validity of the clustering results. These 12 clusters can be further divided into: (I) pulmonary masses, including #0 non-small lung cancer, #1 cancer, #7 pulmonary nodules; (II) ablation treatment methods: #4 cryotherapy, #6 radiofrequency ablation, #11 ablative therapy, #9 minimally invasive surgery; (III) postoperative review and management: #2 management, #5 progression-free survival, #8 magnetic resonance imaging, #10 positron emission tomography; (IV) immune response: #3 dendritic cells.

Analysis of references

A burst strength analysis was conducted using CiteSpace (Figure 9) for the study period from 2002 to 2025 at 1-year intervals, identifying 25 references with notable burst strength. Among these, 5 references have a burst strength greater than 20. Simon CJ, 2007, has the biggest influence with 29.84, followed by Lencioni, R, 2008 (23.27) and Sung H, 2021 (23.12). This analysis identifies the most influential publications in the field over the specified time frame.

Figure 9 The 25 references with the most prominent citation bursts.

Table 6 presents the top 10 most cited literature in the field of lung cancer ablation therapy. Ranked first is “Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines” by John A Howington in 2013, with 1,077 citations and an average of 82.5 citations per year. Six papers were published after 2010. Among them, three articles focus on clinical practice guidelines, two are review articles, and the remaining five are research articles. “Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients”, published by Simon in 2007, is the most influential research article (447 citations). Notably, all research articles are about RFA for lung cancer treatment.

Discussion

Ablation therapy has a history of several decades in cancer treatment, with its fundamental principle being to induce tumor necrosis through extreme heat, coldness and energy changes. In recent years, the number of articles on lung cancer ablation has significantly increased, reflecting growing interest in this field. The effectiveness and safety of thermal ablation for treating lung malignancy have been validated through relevant clinical studies and animal experiments. In a study, patients with early-stage NSCLC underwent RFA before surgical resection, and the pathological examination subsequently confirmed complete tumor necrosis in 6 out of 9 cases (6). Ablation has recently shown good efficacy and superiority in treating high-risk pulmonary nodules, especially for GGNs and multiple lung nodules. Furthermore, in advanced lung cancer, ablation combined with immunotherapy has become a research hotspot. RFA is applied widely as a kind of main and early ablation method. Some relatively new ablation technologies, such as MWA, cryoablation, and electromagnetic navigation bronchoscopic ablation, are being rapidly applied in clinical practice. The development of imaging techniques to evaluate the efficiency of ablation has further promoted the development of pulmonary tumor ablation. The following analysis will be conducted based on the aforementioned key points.

Ablation for early-stage lung cancer

In 2007, Simon published results on RFA for malignant lung tumors. This article has a significant impact, with the strength of citation bursts reaching 29.84 in the strongest citation bursts (Figure 9). It shows that RFA had a 5-year overall survival (OS) rate of 27% for 75 cases of early-stage inoperable NSCLC, while for tumors smaller than 3 cm, more significant survival benefits can be found, preliminarily demonstrating the effectiveness of RFA in treating early-stage lung cancer (7). In 2015, Damian published a prospective multicenter single-arm clinical trial on RFA treatment for early inoperable NSCLC, reporting a 2-year OS rate of 69.8% and a local recurrence rate of 35%. For tumors smaller than 2 cm, the OS rate rises to 78% (8). It is important to note that many early-stage NSCLC patients who cannot undergo surgery may not die from cancer after receiving ablation, but from other diseases (like heart or pulmonary chronic diseases). Another prospective single-arm study further confirms that the 5-year cancer-specific survival (CSS) rate for early-stage lung cancer patients treated with RFA was 40%, and for tumors smaller than 3 cm, this rate increases to 52%. The complete ablation rate is 66%, with the therapeutic advantage of RFA being more prominent in smaller tumors. RFA treatment does not compromise lung function and is well-tolerated, with the incidence of complications requiring treatment being 5% (pneumothorax is the most common) (9).

Similar results have been observed with MWA and cryoablation for early-stage NSCLC. Recent retrospective studies by Peng and Ni show that the 5-year OS rate for MWA ranges from 54.1% to 80.3%. The differences were mainly attributed to patient inclusion criteria and heterogeneity in the ablation process (such as tumor size, proportion of consolidation, ablation power, and standards). Advanced age (over 75 years) does not negatively affect the treatment outcomes, while chronic diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are independent risk factors for survival (10,11). This suggests that for patients with early-stage lung cancer who cannot undergo surgery, the primary threat to patients’ survival may not be the tumor itself, but rather the patient’s overall health status. Additionally, two retrospective studies investigating cryoablation for early-stage NSCLC showed 3-year OS rates of 88% and a 5-year OS rate of 67.8%±15.3% respectively (12,13). Both MWA and cryoablation also demonstrate lower recurrence rates and more significant survival benefits for smaller tumors. In terms of safety, the majority of complications are mild and manageable. However, it should be noted that high-quality studies on the use of MWA, RFA, and cryoablation for early-stage lung cancer are currently lacking, and considerable heterogeneity exists between different studies. Future high-quality research could further explore the effects of ablation on the treatment of early-stage lung cancer.

Comparative study: stereotactic body radiotherapy (SBRT) vs. ablation

Two retrospective studies show that the 5-year OS rates are similar between the thermal ablation (RFA and MWA) and the SBRT for treating early-stage NSCLC, and the recurrence rates are comparable between the MWA and SBRT groups (14,15). A large-scale retrospective analysis utilizing the National Cancer Database (involving 2,204 patients) also shows no significant difference in the 5-year OS rates between thermal ablation and SBRT after propensity score matching (16). However, a meta-analysis indicates that although both treatments have comparable 5-year OS rates for early-stage NSCLC, RFA exhibits lower tumor control rates (17). Another meta-analysis shows MWA has higher tumor control rates and longer OS compared to RFA for early-stage inoperable lung cancer, showing efficacy similar to that of SBRT (18). It’s important to note that most documents in the meta-analysis are single-arm studies, lacking high-quality literature. In terms of safety, pneumothorax is the most common adverse event after percutaneous ablation for lung cancer, occurring in 10–29% of cases, with most requiring no intervention. The most common complication of radiotherapy is radiation-induced lung injury, with the majority being grade 1–2 (about 31%). Although SBRT and ablation therapies yield similar survival results for early-stage lung cancer, SBRT is more effective for larger tumors and offers higher tumor control rates. Further prospective research is required to validate these findings, particularly regarding MWA and SBRT.

Surgery vs. ablation

Currently, comparative studies on surgery and ablation therapy for early-stage NSCLC are predominantly retrospective research. Zemlyak et al. reported that sublobar resection and RFA or cryoablation for inoperable patients with stage I lung cancer show no significant difference in 3-year CSS and OS rates (19). Two retrospective studies comparing lobectomy with MWA for early-stage lung cancer found no significant difference in 5-year progression-free survival (PFS) and OS, which may be attributed to the rigorous patient selection (including some indolent lung cancer patients) and strict ablation criteria (20,21). However, Ambrogi et al. compared wedge resection with RFA for early-stage lung cancer in inoperable patients and found that, regardless of long-term survival or local tumor control, wedge resection was superior to RFA. Notably, patients in the RFA group had worse baseline characteristics, including older age, more comorbidities, and poorer performance status, compared to those in the surgical group (22). Yim compares the treatment results of wedge resection and thermal ablation for early-stage lung cancer based on the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching, two methods showed similar OS and CSS rates for tumors under 1 cm. In patients with tumors ranging from 1 to 2 cm, thermal ablation was significantly associated with worse OS (23).

The existing retrospective studies exhibit considerable heterogeneity. Differences in outcomes may be related to various factors, such as patient selection, ablation techniques, and intraoperative evaluation criteria of ablation effect. The prevailing academic consensus is that surgical resection remains the primary treatment for early-stage lung cancer, with SBRT currently recommended as the main alternative therapy for inoperable patients, as several high-quality studies have confirmed that SBRT is not inferior to surgery in controlling early-stage lung cancer (24,25). The advantage of surgical resection lies not only in the removal of the tumor but also in the lymph node dissection, which cannot be achieved by ablation. However, due to compromised cardiopulmonary function or concurrent comorbidities, approximately 30% of patients with early-stage lung cancer are unable to undergo surgical resection and instead require alternative local treatments (26).

Ablation therapy offers the advantage of enabling repeated treatments for patients who do not achieve complete ablation. For early-stage NSCLC that recurs after MWA, re-ablation can yield survival outcomes similar to those in patients without recurrence (27). Additionally, for lung cancer patients with IPF, neither cryoablation nor thermal ablation exacerbates IPF, unlike radiation therapy, making ablation more suitable for these patients (28,29).

Smaller tumors are more likely to be completely ablated. For smaller lesions (<2 cm), the risk of lymph node metastasis is low. Data from the JCOG0802 trial indicate a 5.9% lymph node metastasis rate for stage I lung cancer with tumor size ≤2 cm and a consolidation tumor ratio (CTR) >0.5 (30). Moreover, a prospective multicenter randomized controlled study conducted by Zhang and colleagues further confirms that for patients with CTR ≤0.5 and cT1N0 stage, no mediastinal lymph node metastasis and systematic mediastinal lymph node dissection may not even be necessary during surgical operation (31). Therefore, whether ablation therapy achieves curative effects for such patients who are ineligible for surgery? This question requires further exploration through prospective studies.

Ablation for ground glass nodules

With the growing use of high-dose chest CT scans and heightened awareness of population health check-ups, the detection of GGNs is increasing. Stable pure GGN is mostly atypical hyperplasia, adenocarcinoma in situ, or minimally invasive adenocarcinoma. There is still controversy about the treatment of such pulmonary nodules. Current recommendations recommend surgical treatment of GGNs that grow or develop into solid components during follow-up (32-34). Some studies show that ablation exhibits high efficacy in treating this type of nodule. Yang first reported the use of MWA to treat pulmonary GGN in 2018. In this study with 52 patients, the 3-year PFS is 98%, CSS is 100%, and OS is 96%. The most common postoperative complication is pneumothorax, in which 5 patients (9.8%) required a chest drain (35). Subsequently, the team published a multicenter study in 2023 involving 87 patients with long-term follow-up, which shows that MWA for pathologically confirmed malignant GGNs has an excellent prognosis, with a 5-year CSS rate of 100% and a 5-year local PFS rate of 96.6% (36). In a study comparing RFA with sublobectomy for GGN-dominant pulmonary nodules, no distant metastases or local recurrence occurred in either group during the 24–30 months follow-up. In addition, the thermal ablation group has significantly fewer complications, shorter operative times, and hospital stays (37,38). Liu et al. utilized cryoablation to treat patients with lung nodules composed mainly of GGN, and it also showed good safety and efficacy. Following a mean follow-up of 24 months, no recurrence was observed (39). Current studies have shown that different ablation types show good efficacy for high-risk ground-glass pulmonary nodules.

Ablation combined with surgery for multiple pulmonary nodules (MPNs)

MPNs are not uncommon. According to large-scale long-term follow-up data from Europe, 12.8% of patients with lung nodules had multiple nodules (pure GGN or partially solid nodules) (40). Most long-existing pure GGNs are malignant and inert; follow-up observation should be the primary method. However, in a study with 3 years of follow-up, 32% of patients with MPNs progressed, and 41% of the remaining nodules continued to progress after the first pulmonary nodule progressed (41). Especially for partially solid nodules, the degree of malignancy is higher than that of pure GGNs (42). According to the guidelines for treating multiple high-risk lung nodules, the treatment should focus on the dominant lesion first (such as those with a larger diameter or more solid components), and surgery is still the first choice. However, for multiple high-risk nodules located bilaterally or in different lobes, surgery may result in over-resection, impairing lung function and life quality. Recently, Huang and colleagues explored a combined MWA and surgical treatment option to address this issue. This method involves surgical removal of the dominant lesion (e.g., needle signs, lobular signs, vacuolar signs, and tumors with a CTR greater than 50%). Surgical strategies are determined by the lesion’s location, with wedge resection or segmentectomy being the preferred surgical method to preserve lung function. For inert lesions (e.g., pure GGN), scheduled multiple MWA treatments were used after surgery. The study involved 47 patients, none of whom experienced recurrence during the follow-up, with a 5-year OS rate of 97.5% (43). Other researchers have also explored different combination treatment options. Zhang and colleagues chose simultaneous ablation and surgery. Percutaneous RFA of lung nodules was performed under local anesthesia preoperatively, followed by video-assisted thoracoscopic surgery (VATS) under general anesthesia to treat the primary lesion. The overall complication rate is 9.5% (10/105), and most cases were treatment-free (44). Combined strategies of surgery and ablation have great potential and may solve the challenges of treating MPNs in the future (45).

Ablation for advanced NSCLC

Currently, chemotherapy remains a key treatment for patients with advanced lung cancer lacking sensitive gene mutations. One randomized controlled trial demonstrates that patients with advanced lung cancer treated with MWA and chemotherapy had better OS and PFS compared to those receiving chemotherapy alone, without a significant increase in adverse events (46). RFA has also shown similar survival benefits when combined with chemotherapy for patients with advanced NSCLC (47,48). Another multicenter randomized controlled study shows that in advanced NSCLC patients who failed first-line chemotherapy, the addition of cryoablation improved disease control rate (DCR) and quality of life, although no difference in OS was observed, which may be related to the tumor’s advanced stage (49). This suggests that in advanced NSCLC patients, the prognosis is more effectively improved by combining ablation therapy with chemotherapy than by chemotherapy alone. This may be because ablation reduces the tumor burden while stimulating the immune system, enhancing the anti-tumor effect, and synergizing with chemotherapy.

Ablation combined with targeted therapy

For patients with advanced NSCLC with epidermal growth factor receptor (EGFR) mutations, the first-line treatment is tyrosine kinase inhibitors (TKIs). But can the combination of ablation therapy further improve the patient’s prognosis? Some studies have explored MWA or RFA combined with TKIs as the primary approach for patients with advanced EGFR-mutated NSCLC. This combination treatment significantly improves related prognostic indicators such as OS and PFS when compared to TKI therapy alone (50,51). Following the failure of first-line targeted treatment, the use of ablation therapy can also improve patient survival. In one study, the addition of MWA can prolong the median PFS of patients by 10 months (52). In patients with oligo-progression outside the central nervous system (CNS) during targeted therapy, the combination of MWA and original TKIs significantly prolonged PFS (8.8 vs. 5.8 months) and improved OS (27.7 vs. 20.0 months) compared to chemotherapy (53). Based on the current findings, combining ablation therapy with targeted therapy may offer additional survival benefits for patients with first-line EGFR mutations as well as those with oligo-progression outside the CNS following TKI resistance. The direct reason is that ablation treatment destroys the primary or metastatic tumor site. At the molecular level, two methods also show synergistic effects. In a basic study, it was found that thermal ablation reduces osimertinib resistance through the EGFR/PI3K/AKT/HIF-1α signaling pathway to enhance the sensitivity of osimertinib-resistant NSCLC cells to osimertinib. On the other hand, by targeting the same pathway in the transition zone, osimertinib can effectively prevent recurrence after ablation, thereby demonstrating a synergistic antitumor effect (54).

Ablation combined with immunotherapy

Ablation can trigger a significant immune response, destroy tumor cells and release tumor-associated antigens, thereby activating the cancer immune cycle, and can convert immune deserts or immuno-excluded tumors into an immuno-inflammatory phenotype.

Case reports have indicated that combining ICIs with thermal ablation produces an abscopal effect and lasting antitumor effect in advanced NSCLC (55). Recently, a phase 2 randomized trial (BOOSTER) showed that treating advantaged NSCLC patients with oligo-residual disease after anti-PD-1/L1 therapy with MWA or cryoablation can significantly prolong PFS and OS compared with immunotherapy alone, and the cryoablation group yields a superior survival benefit than MWA. The majority of ablation-related adverse events are tolerable and controllable, with only one case (2.3%) of pneumothorax classified as grade 3 or higher (56). Several retrospective studies have investigated the use of MWA combined with immunotherapy in advanced NSCLC. The objective response rate (ORR) was 29.9–33.3%, and the PFS ranged from 7.9–11.8 months. However, the prognosis is not related to the presence of CD8⁺ tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1) in these patients, possibly due to limitations in sample size (57,58). Although thermal ablation combined with ICIs can improve immune status, whether this method can produce synergistic antitumor effects needs future basic research to confirm.

Cryoablation can better preserve relevant protein antigens than thermal ablation, and theoretically can enhance antitumor effects when combined with immunotherapy. A randomized controlled study demonstrates that for patients with advanced NSCLC, cryoablation combined with PD-1 inhibitor therapy can significantly improve PFS and OS compared to the PD-1 inhibitor plus chemotherapy group, along with a notable enhancement in immune function (significant increase in CD4⁺ and CD4⁺/CD8⁺ ratios) (59). Lin and colleagues were the first to evaluate cryoablation combined with allogeneic NK cell immunotherapy in advanced NSCLC. The results demonstrate that this combination significantly enhanced ORR and the DCR (60). Vasiliauskas and colleagues randomly divided 55 patients with metastatic NSCLC into two groups: one receiving bronchoscopic cryoablation and the other receiving control treatment. Each group received up to four cycles of pembrolizumab with or without chemotherapy. The cryoablation group has a significantly higher DCR compared to the control group (95.2% vs. 73.1%) (61). In addition, the animal experiment demonstrates that cryoablation can trigger abscopal immune-regulatory effects, and combining ICIs could further inhibit tumor progression. This comes true by triggering type I interferon-dependent antitumor immunity (62).

In recent years, the combination of immunotherapy and ablation therapy for advanced NSCLC has emerged as a prominent research focus. Theoretically, ablation combined with immunotherapy can improve immune function and synergistically enhance anti-tumor effects. More research is still needed in the future to strengthen this conclusion (e.g., NCT06127303, NCT06604351 are underway).

Evaluation of ablation effect

Intraoperative evaluation

The ablation zone of lung tumor expresses “halo effect” in imaging, and it’s the primary assessment criterion for the ablation effect during operation. Histopathology describes the halo effect surrounding the tumor after thermal ablation as a three-layer concentric structure: the inner layer consists of an eosinophilic cytoplasmic area with preserved structure, the middle layer is the alveolar exudate area, and the outer layer is the pulmonary tissue with congestion, hemorrhage, and neutrophil infiltration. The inner and middle layers are completely necrotic, while the outer layer retains cellular activity, meaning that the tumor cells in the outer layer are not fully eradicated (63). It is known that incomplete coverage of the halo after ablation is a common site for tumor recurrence. However, there is no unified standard for the extent of ablation required for complete tumor ablation. Several studies suggest that the halo from thermal ablation should be at least 5 mm beyond the tumor, while others indicate that this ablation area should extend 5–10 mm beyond the lesion, and some studies even suggest that it should be at least 10 mm (64-66). In fact, the evaluation of the ablative effect relies on the lesion characteristics and the type of ablation used. For solid component lung tumors, the ablation time and intensity must be higher than for subsolid pulmonary nodules. Meanwhile, thermal ablation can cause varying degrees of tissue shrinkage, especially for GGNs, which shrink more significantly. Studies show that the shrinkage rate of lung nodules after ablation ranges from 0% to 43% according to the nodules’ characteristics, which should be considered when evaluating the adequacy of the margins (67). Additionally, different ablation techniques yield different effects. RFA is easily influenced by the heat sink effect, while MWA is less affected due to its different heating principles. Cryoablation is assessed by the ice ball, with complete ablation defined as the area within 5 mm of its edge (68). However, bleeding during ablation caused by physical damage from the needle and temperature changes may result in similar density on images, complicating the accurate assessment of the tumor location and margin. One study explored preoperative and immediate postoperative CT image fusion to evaluate the tumor’s location and then estimated whether the ablation zone fully covered the lesion by identifying surrounding anatomical structures (like vessels or bronchus). The results show that immediate post-ablation image fusion revealed a complete ablation rate of 93.5%, consistent with the 6-month postoperative CT recheck results. The sensitivity and specificity are both 100%, demonstrating that this method improves the accuracy of determining complete ablation of the tumor (69). In the future, more advanced imaging technologies can be explored to assess the ablation area by comparing pre- and post-ablation imaging changes, thus improving intraoperative accuracy and efficacy of ablation.

Postoperative evaluation

Local recurrence in the ablation zone is the most frequent form of recurrence following ablation therapy (70). Imaging remains the primary method for evaluating the long-term effects of ablation treatment. Typically, contrast-enhanced computed tomography (CT) is performed at 1, 3, 6, 9, 12, 18, and 24 months, followed by annual checks. After thermal ablation, various imaging findings can be observed. Immediately after the procedure, an oval or wedge-shaped, well-defined ground-glass area surrounding the lesion is visible. During later follow-up, as hemorrhage, congestion, and edema subside, the peripheral ground-glass opacity gradually dissipates, and the central ablation zone contracts, forming a fibrotic scar or even disappearing. Pulmonary nodules with a peripheral enhancement of 15 Hounsfield units (HU), appearing crescent-shaped, nodular, or irregular during follow-up, suggest incomplete ablation (71,72). In cryoablation, the ice ball is used to assess the ablation effect. After thawing, the ablation zone is characterized by a central solid area surrounded by a peripheral ground-glass region. The imaging changes during subsequent follow-up are similar to those seen in thermal ablation. If enlargement or uneven enhancement is observed during recheck, tumor recurrence should be suspected (65).

In recent years, more and more imaging technologies and methods have been applied to evaluate lung cancer after ablation therapy, aiming to identify recurrent tumors earlier and provide timely treatment. Postoperative positron emission tomography (PET)-CT rechecks provide higher accuracy than CT, with maximum standardized uptake value (SUVmax) serving as a useful, reliable, and objective predictive marker. This method is recommended 3 to 6 months after ablation (73,74). Dual-energy CT (DECT) is a relatively new technique that can provide more detailed tissue characterization of iodine-enhanced structures, which facilitates the detection of enhancement within suspicious regions and necrotic tissue post-RFA (75). Radiomics can extract and analyze lesion characteristics from images, providing detailed information beyond what is visible to the human eye, and can predict malignancy or treatment response. In recent years, the evaluation of treatment effects in lung tumor ablation using radiomics has been explored by some researchers. Liu et al. analyzed the changes in tumor density on CT images before and after ablation and found that the Δcontrast% indicator is a good predictor of local tumor progression at 1 year, with a sensitivity of 83.5% and specificity of 87.1%. It can predict treatment response and local tumor progression earlier, especially for larger tumors (76). Ma et al. combined clinical and radiomic factors to provide a diagnostic tool for predicting recurrence after MWA for early-stage lung adenocarcinoma, achieving an area under the curve (AUC) of 0.90 and 0.89 in the internal test set and the external test set (77). Similarly, Zhu et al. developed a model using four selected radiomic features that accurately identifies patients at high risk of recurrence after MWA (AUC: 0.896) (78). Combining imaging and machine learning can also better predict the effectiveness of ablation treatment. Zhou et al. used the improved U-NET algorithm to effectively identify lesions and assess the therapeutic effect after RFA with accuracy (79). With advancements in imaging technology, radiomics, machine learning, and other analytical methods, researchers can more precisely evaluate lung tumor ablation outcomes, guiding subsequent treatment plans.

Application of ablation techniques

Compared to the liver and kidneys, lung tissue has its unique characteristics. First, because the lungs are air-containing tissues, this limits the application of high-energy ultrasound. As a result, high-energy ultrasound for lung ablation is primarily used in in vitro studies. Additionally, lung tissue exhibits low electrical conductivity and heat insulation properties, which enable a larger volume of tissue to be ablated at a given energy level compared to other organ tissues in the body (80).

RFA is the earliest and still the primary method for lung ablation. Its principle is that under the action of high-frequency alternating current, ions within tumor tissues collide and rub, generating heat. When the temperature exceeds 55 ℃, protein denaturation is induced, leading to subsequent coagulative necrosis. However, it is limited by the thermal sinking effect, and the likelihood of incomplete ablation increases in nodules near blood vessels and airways (81).

Recently, a growing number of studies have explored MWA for lung cancer. The principle underlying this process is that, under the influence of microwave electromagnetic fields, polar molecules like proteins and water rapidly vibrate, causing molecular friction and collisions, and leading to a rapid increase in temperature to 60–150 ℃, which ultimately results in tumor coagulative necrosis. It generates higher temperatures in a short time, a larger ablation area, and a reduced thermal sinking effect compared to RFA, which may explain why it is being increasingly applied by more researchers (11,82).

Cryoablation has gained more attention in recent years, including argon-helium cryoablation and liquid nitrogen cryoablation. The principle is to create extremely low temperatures within the tumor tissue (as low as −196 ℃) and then rapidly rewarm it (up to 80 ℃), causing protein denaturation, cell rupture, and ischemic reactions, while releasing antigens that trigger immune responses. Its benefit is the significant reduction in pain during the ablation process, unlike thermal ablation. The downside is a longer procedure or increased complications, such as hemoptysis (83,84).

Laser ablation is mainly used for airway obstruction caused by tumors, usually in combination with endoscopy, where high-energy light can coagulate and vaporize tumors. The neodymium-yttrium aluminum garnet (Nd:YAG) laser has been used in most studies due to its superior coagulation effect over cutting, and it can rapidly alleviate severe dyspnea caused by tumor obstruction (85).

PEF ablation uses short-duration, high-voltage electrical pulses to induce cell death. Unlike other ablation methods, this approach is characterized by preserving the stromal proteins and extracellular matrix, thereby protecting critical structures such as blood vessels and lymph nodes, promoting the chemotaxis of immune cells to the ablation area, and enhancing anti-tumor activity. Jimenez et al. are the first to apply PEF technology in human trials. Thirty-six patients with early-stage NSCLC underwent PEF ablation before surgery. Through pathological examination of post-resection tissue in the tumor and ablation zones, the ablation zone in tumors was essentially nonviable. Additionally, tertiary lymphoid structures were observed within the ablation zone, which were associated with immune responses (86). Moore et al. found that combined PEF with basic therapy was a more suitable second-line treatment for advanced NSCLC than basic therapy only, demonstrating significantly improved 1-year OS (74.3% vs. 33%) and PFS (63.2% vs. 18%) (87). PEF ablation shows promising prospects for treating lung cancer. However, the drawback of this technique is that the high impedance characteristics of lung tissue could impact efficacy by interfering with electrical pulse conduction. Unlike thermal ablation, it does not produce coagulative necrosis and is prone to pneumothorax and needle tract metastasis.

Comparative studies of different ablation methods

A randomized controlled trial (the LUMIRA trial) comparing MWA and RFA for lung cancer treatment shows that both significantly reduced tumor size one year later, with no difference in survival rates. However, patients in the MWA group experienced notably less pain (88). A meta-analysis by He and colleagues, involving 33 studies, finds no significant difference in 5-year CSS and OS between MWA and RFA for treating stage I NSCLC. However, most of the studies included were retrospective single-arm studies (89).

A comparative study of RFA and cryoablation for stage I NSCLC shows that the RFA group had a lower incidence of pneumothorax and pleural effusion than the cryoablation group, along with a shorter surgical time. However, the RFA group experienced a higher incidence of intraoperative pain. Two groups show no statistically significant difference in the 1-, 3-, and 5-year DFS and OS (90). A meta-analysis comparing cryoablation and RFA for lung cancer reveals that cryoablation has superior 3-year DFS and lower complication rates compared to RFA. Additionally, cryoablation significantly reduces recurrence rates and improves prognosis (91).

One retrospective study comparing cryoablation and MWA for primary pulmonary high-risk nodules shows that the cryoablation group has relatively lower local disease progression rates (12.12% and 7.41%) with a median follow-up of 25 months. Besides, cryoablation significantly reduces procedural pain (92). The incidence of postoperative bleeding was higher in the cryoablation group compared to the MWA group (93).

Each ablation method has its own strengths and limitations, and further high-quality research is needed to determine which method offers superior ablation outcomes.

Ablation pathways and methods of imaging-guidance

Currently, percutaneous lung puncture for ablation therapy is the mainstream approach for lung cancer. However, this method has a high risk of pneumothorax and intrathoracic bleeding. In recent years, bronchoscopic transbronchial ablation techniques have thrived and become a new trend of lung cancer ablation. The advantage of this approach is that it can reach specific areas in the lung that are challenging to access by the pleural route. It also avoids obstruction from ribs or scapulae, significantly reducing the risk of pneumothorax and intrathoracic bleeding (94). A multi-centre, large-scale clinical trial (BRONC-RFII) demonstrates that bronchoscopic RFA achieved a success rate of 99.35% for lung tumor ablation. In the 1-year follow-up, the complete ablation rate was 90.48%, with pure GGNs showing better outcomes than solid nodules (95). A retrospective analysis compared the efficacy of percutaneous or bronchoscopic ablation for early-stage lung cancer. The one-year tumor control rate and PFS were similar between the two groups. However, the incidence of pain and pneumothorax was significantly greater in the percutaneous ablation group compared to the bronchoscopic transbronchial MWA group (96). Bronchoscopic-guided thermal ablation demonstrates good safety and feasibility, whether under cone-beam computed tomography (CBCT) guidance or electromagnetic navigation guidance (97). But compared to percutaneous lung nodule ablation, it is slightly less precise in locating smaller peripheral pulmonary nodules (67).

At present, multi-detector-row computed tomography (MDCT) guided puncture for pulmonary tumors is the most widely employed imaging method. MDCT provides high-resolution images that facilitate precise needle placement into the target tumor, but the procedure is complex, and patients are exposed to high radiation. Recently, CBCT has been increasingly adopted to guide ablation of pulmonary tumors owing to its real-time imaging capability and flexible multi-angle needle insertion. The built-in virtual navigation system also aids needle pathway planning and improves targeting accuracy. In a study comparing MDCT- and CBCT-guided lung lesion biopsies, CBCT guidance achieved higher puncture accuracy and shorter procedure times (98). Several retrospective studies have demonstrated that CBCT-guided ablation of lung lesions is relatively safe, with manageable complications (98,99). However, CBCT has lower spatial resolution and performs less well in detecting small or subsolid nodules. The choice of method should be determined based on the tumor’s location and size.

Limitations

There are certain limitations to the bibliometric analysis presented in this article. (I) This study aims to provide an overview of research on lung cancer ablation therapy, and there are few literatures published before 2002, so we defined the time frame as 2002–2025; (II) the literature search was based solely on the Web of Science Core Collection (WoSCC), and any literatures related to this field but not included by this database could result in selection bias and analytical errors.

Conclusions

This article summarizes the current research status and proposes new directions and ideas for lung cancer ablation treatment, such as: (I) exploration of combined treatments for patients with multiple primary lung cancers; (II) further exploration for patients with early-stage lung cancer; (III) the combination of ablation and immunotherapy for patients with advanced lung cancer; (IV) Improving the accuracy of ablation zone assessment in intraoperative and postoperative imaging; (V) endoscopic ablation via the trachea as a new option for ablation treatment. These findings will help promote future scientific research progress.

Acknowledgments

None.

Footnote

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Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2172/coif). The authors have no conflicts of interest to declare.

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