Abstract
Background
Ablation is an effective alternative treatment option for early-stage non-small cell lung cancer (NSCLC) patients who are not candidates for surgery or who refuse surgery. Microwave ablation (MWA) and cryoablation (CA) are both minimally invasive treatment techniques widely used in NSCLC patients, and their safety and efficacy have been verified. This study aimed to compare the safety and efficacy of co-ablation (Co-A) and MWA in the treatment of subpleural stage I NSCLC.
Methods
From December 2023 to December 2024, a retrospective analysis was conducted on 87 eligible patients (40 males, 47 females; mean age ± standard deviation: 72.03±9.07 years; age range, 31–88 years). Patients were divided into two groups based on the treatment method: a Co-A group and an MWA group. Recurrence-free survival (RFS) rates and complication rates were compared between the two groups.
Results
Co-A had a significantly longer mean operative time compared to MWA (28.26±7.56 vs. 6.37±2.01 min, P<0.001). Postoperative analgesic intervention was significantly lower in the Co-A group (30.4% vs. 45.4%, P=0.03). Mean follow-up time was similar between groups (7.04±2.01 vs. 7.27±2.49 months, P=0.69). RFS rates at study end were 95.7% in Co-A and 100.0% in MWA (P=0.26). Common complications—pneumothorax, transient hemoptysis, and pleural effusion—showed no significant differences in incidence between the two groups (P>0.05). However, pneumothorax requiring chest tube drainage was significantly higher in the Co-A group (34.8% vs. 7.8%, P=0.008).
Conclusions
Compared with MWA, Co-A demonstrates no significant difference in efficacy or safety for treating patients with subpleural stage I NSCLC, but is associated with reduced perioperative pain and a longer operative duration.
Keywords: Microwave ablation (MWA), co-ablation (Co-A), non-small cell lung cancer (NSCLC), subpleural
Highlight box.
Key findings
• Co-ablation (Co-A) for subpleural stage I non-small cell lung cancer demonstrates comparable safety and efficacy to microwave ablation (MWA), with a lower incidence of intraoperative pain and good patient tolerance.
What is known and what is new?
• The low-density ice ball formation of Co-A can be monitored through dynamic computed tomography scanning, making it relatively safer for lung nodules adjacent to the heart and major blood vessels.
• Co-A has better intraoperative analgesic effects, which can improve patients’ cooperation during surgery.
What is the implication, and what should change now?
• The selection and application of Co-A or MWA should be determined based on tumor location, risk of complications, patient comorbidities, and the expertise of the interventional radiologist. Regarding the rate of pneumothorax requiring chest tube drainage is higher with Co-A, we recommend the following procedural modifications to mitigate the risk of pneumothorax in future: employing a more meticulous puncture technique to minimize lung injury with the guidance of puncture navigation devices, using smaller Co-A probes, and applying artificial pneumothorax or artificial pleural effusion technique for tumors near the pleura.
Introduction
Lung cancer is one of the most frequently diagnosed malignancies and a significant global public health concern and research priority. Non-small cell lung cancer (NSCLC) constitutes over 80% of all lung cancer diagnoses, with stage I NSCLC representing 15% to 20% of these cases (1). While surgical resection remains the gold-standard treatment for early-stage lung cancers, some patients with early-stage disease, due to multiple comorbidities, compromised physical condition, and impaired cardiopulmonary function, may not be eligible for or may decline surgical intervention (2). Consequently, thermal ablation techniques, including radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA), have emerged as viable alternatives, demonstrating control rates comparable to those achieved with surgery. These techniques are primarily utilized for the curative treatment of primary lung cancer with a maximum tumor diameter of ≤3 cm, or for lung metastases in cases where the primary tumor is controlled. Furthermore, they are employed for the palliative treatment of primary lung cancer with a maximum tumor diameter >3 cm and for lung cancer that has progressed or recurred following other treatment modalities (3). In comparison to RFA, MWA is a minimally invasive technique characterized by faster procedural times, larger ablation volumes, and a reduced “heat sink” effect (4). CA, on the other hand, ablates lesions with well-defined margins by forming an ice ball at the tip of the probe (5). Furthermore, the extremely low temperature provides an analgesic effect, thereby improving patient tolerance. Co-ablation (Co-A), a technology developed by a Chinese research team, is capable of reaching even lower temperatures (6). To further investigate the efficacy and safety of Co-A using liquid nitrogen in the treatment of subpleural stage I NSCLC, this study comparatively analyzed the recurrence-free survival (RFS) rates and complication rates of two ablation methods. The primary aim of this investigation is to provide evidence-based reference for the selection of appropriate treatment protocols for subpleural stage I NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-296/rc).
Methods
Patients
The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The medical research ethics committee of Beijing Hospital approved the study (No. 2024BJYYEC-KY021-01), and the requirement for informed consent was waived due to the retrospective nature of this study. A retrospective review of electronic medical records and computed tomography (CT) images was conducted at our institution’s therapy center to identify patients with inoperable subpleural stage I NSCLC.
The eligibility criteria were as follows: (I) pathologically confirmed NSCLC, I stage [American Joint Committee on Cancer (AJCC) 9th edition] as determined by positron emission tomography (PET)-CT, enhanced-contrast CT, or brain magnetic resonance imaging (MRI); (II) the tumor is located in the subpleural: the edge of the cancer is ≤10 mm from the pleura on the CT lung window image; (III) Eastern Cooperative Oncology Group performance status (ECOG PS) score: 0 to 2; (IV) inability to tolerate or refuse of surgery and radiotherapy; and (V) available CT image data at our therapy center.
The exclusion criteria were as follows: (I) severe hemorrhage, coagulation disorders, or platelet count <50×109/L; (II) ECOG PS score ≥3; (III) patients with severe infection, fever (>38.5 ℃), skin infection and ulceration at the puncture site; (IV) with other malignancies or severe multi-organ dysfunction; (V) the patient’s expected survival is less than 3 months; and (VI) inability to cooperate with outpatient or telephone follow-up.
Between December 2023 and December 2024, a cohort of 87 patients with subpleural stage I NSCLC was included in this study. Of these, 23 patients underwent Co-A and 64 patients underwent MWA.
Devices and procedure
All procedures were performed under CT guidance using a Discovery 16-Slice CT scanner (GE HealthCare; Chicago, IL, USA). Most procedures were performed under local anesthesia with subcutaneous 1% lidocaine. General anesthesia and intercostal nerve block anesthesia were not routinely employed. In accordance with the guidelines established by the Society of Interventional Radiology, ablation procedures were performed by experienced interventional radiologists with over 5 years of experience. Flurbiprofen axetil (5 mg, intravenous) was administered during the treatment. The optimal patient positioning on the CT bed was determined based on tumor location. Continuous electrocardiographic monitoring, including heart rate, blood pressure, respiration rate, and pulse oximetry, was performed intermittently throughout the procedures.
Co-A procedures
All Co-A procedures were performed using a nitrogen-ethanol-based HJY CHS 800001 Co-A system (HYGEA Medical Technology Co., Beijing, China) (Figure 1). Based on the Phase-Transition principle, liquid nitrogen was delivered into the probe, decreasing the temperature to as low as −196 ℃ as it transitioned from a liquid to a gas phase. During the active thawing phase, ethanol was circulated within the tip of the probe, increasing the probe temperature to as high as 80 ℃ upon transition from a gas to a liquid phase within the probe. The flow of both nitrogen and ethanol was controlled by a computer-modulated device integrated into the system. The 14-gauge (G) probe had an outer diameter of 1.98 mm and a length ranging from 120 to 180 mm. Co-A parameters, including the number of sessions and duration, were determined based on tumor size, shape, and location. A freezing phase and an active thawing phase were performed in a cyclical pattern. Typically, two to three cycles were performed per session. Throughout the ablation procedure, intermittent non-contrast CT scans (every 5–10 min) were performed to monitor the coverage of the ice ball. The effective ablation margin was targeted to extend beyond the tumor edge by at least 5 to 10 mm. CT imaging was performed immediately post-procedure to assess the ablation zone and identify potential complications. Complications associated with the ablation procedure were recorded during the perioperative period.
Figure 1.
CT images of a 67-year-old female with stage IA NSCLC (adenocarcinoma) who underwent CT-guided Co-A in our treatment center. (A,B) CT prior to Co-A treatment showed a 1.3 cm × 1.1 cm subpleural lesion (arrows) in the right upper lobe. (C) She underwent CNB with an 18-G automated biopsy gun. (D-F) Then, the 14-G co-probe was step-introduced to ablate the lesion. (G-I) The ablation procedure was ceased when the ice-ball extent exceeded the lesion margin by 1 cm. (J) CT image 24 h post-procedure showed ground-glass opacity around the tumor. (K) The 1-month CT image after Co-A treatment revealed gradual shrinkage of the ablated lesion. CNB, core-needle biopsy; Co-A, co-ablation; CT, computed tomography; NSCLC, non-small cell lung cancer.
MWA procedures
After anesthesia, a 15-G coaxial introducer needle (Argon Medical Device, Plano, TX, USA) was step-advanced to the edge of the tumor. The MWA system MTC-3C (Vison-China Medical Devices, Nanjing, China) or ECO-100A1 (ECO Medical Instrument, Nanjing, China) was used to perform the ablation procedures. The microwave antenna has an effective length of 15–18 cm, an outer diameter of 17–18 G, and a head end of 15 mm. A contrast-enhanced CT scan was performed preoperatively to locate the lesion, design the puncture point, plan the optimal puncture path, and decide on the number of MWA antennas. MWA antenna was introduced through the coaxial cannula to perform ablation. The ablation power output was set to 30–40 W, and the duration ranged from 5 to 20 min. In all cases, the antenna was adjusted as needed for multi-sites ablation to extend 5–10 mm beyond the lesion’s periphery. At the end of the procedure, a needle tract embolization was performed with 1,400–2,000 µm gelatin sponge particle suspension while retrieving the coaxial cannula. Chest plain CT was reviewed immediately after MWA to assess the extent of the ablation and to exclude potential complications.
Evaluation and follow-up
Contrast-enhanced CT was performed at 1, 3, and 6 months and then every 6 months thereafter based on guidelines and consensus recommendations. PET-CT was performed if necessary for cases with suspected local recurrence of the tumor or distant metastases. Technical success was defined as the depicted ablation zone entirely encompassing the tumor. Technical efficiency indicated that tumors completely encompassed by the ablation area, as evaluated by CT imaging one month after the procedure, were deemed successful. Local recurrence was defined as enlarged ablation area, irregular nodules at the edge of the ablation zone, or abnormal enhancement of the ablation zone on CT images. The safety assessment focused on treatment-related adverse events occurring within 30 days after ablation. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (7).
Statistical analysis
All data were analyzed using SPSS for Windows version 25.0 (IBM, Armonk, NY, USA). Normally distributed continuous variables were presented as the mean ± standard deviation, skewed distributed continuous variables were presented as the median (25th–75th), and categorized variables were expressed in percentages. All categorical variables were compared using Pearson’s Chi-squared test or Fisher’s exact test, and all continuous variables were compared using the Student’s t-test. All tests were two-sided, and P values <0.05 were considered to be statistically significant. We used 3D Slice version 5.9.0 to measure the ablation area.
Results
The main reasons for ablation
As shown in Table 1, the main reasons for ablation were as follows: advanced age, n=76 (87.4%); refused surgical or radiotherapy, n=40 (46.0%); cardiac insufficiency, n=30 (34.5%); etc.
Table 1. Main reasons for ablation.
| Main reason for ablation | N (%) |
|---|---|
| Refused surgical or radiotherapy | 40 (46.0) |
| Advanced age | 76 (87.4) |
| Cardiac insufficiency | 30 (34.5) |
| Cerebral infarction | 11 (12.6) |
| Pneumonectomy history | 3 (3.4) |
| Pulmonary comorbidity | 19 (21.8) |
Patients and tumor characteristics
Eighty-seven patients (40 men and 47 women) underwent pulmonary ablation for clinical stage I NSCLC (81 patients with stage IA and 6 patients with stage IB). The mean age was 72.03±9.07 years. The mean diameter of tumors was 1.86±0.75 cm. Pathological findings confirmed adenocarcinoma in 77 (88.5%), squamous cell carcinoma in 9 (10.3%), and sarcomatoid carcinoma in 1 (1.1%) of the patients. The detailed characteristics of the patients and tumors are summarized in Table 2.
Table 2. Clinical characteristics of patients.
| Parameters | All (n=87) | Group Co-A (n=23) | Group MWA (n=64) | P value |
|---|---|---|---|---|
| Age (years) | 72.03±9.07 | 70.91±12.71 | 72.88±7.39 | 0.49 |
| Gender | 0.78 | |||
| Male | 40 (46.0) | 10 (43.5) | 30 (46.9) | |
| Female | 47 (54.0) | 13 (56.5) | 34 (53.1) | |
| Smoking history | 31 (35.6) | 7 (30.4) | 24 (37.5) | 0.54 |
| Pathology | 0.10 | |||
| Adenocarcinoma | 77 (88.5) | 18 (78.3) | 59 (92.2) | |
| Squamous cell carcinoma | 9 (10.3) | 5 (21.7) | 4 (6.3) | |
| Sarcomatoid carcinoma | 1 (1.1) | 0 (0.0) | 1 (1.6) | |
| Comorbidities | ||||
| IPF | 7 (8.0) | 4 (17.4) | 3 (4.7) | 0.08 |
| Diabetes | 24 (27.6) | 3 (13.0) | 21 (32.8) | 0.03 |
| COPD | 14 (16.1) | 5 (21.7) | 9 (14.1) | 0.51 |
| Hypertension | 42 (48.3) | 7 (30.4) | 35 (54.7) | 0.055 |
| Atrial fibrillation | 3 (3.4) | 1 (4.3) | 2 (3.1) | >0.99 |
| Pacemaker implantation | 1 (1.1) | 0 (0.0) | 1 (1.6) | 0.51 |
| CAD | ||||
| PCI | 10 (11.5) | 1 (4.3) | 9 (14.1) | 0.28 |
| CABG | 1 (1.1) | 0 (0.0) | 1 (1.6) | >0.99 |
| Cerebral infarction | 11 (12.6) | 3 (13.0) | 8 (12.5) | >0.99 |
| Pneumonectomy | 0.01 | |||
| Ipsilateral | 7 (8.0) | 5 (21.7) | 2 (3.1) | |
| Contralateral | 8 (9.2) | 3 (13.0) | 5 (7.8) | |
| Tumor size (cm) | 1.86±0.75 | 1.87±0.92 | 1.85±0.69 | 0.89 |
| Clinical stage | 0.19 | |||
| IA | 81 (93.1) | 20 (87.0) | 61 (95.3) | |
| IB | 6 (6.9) | 3 (13.0) | 3 (4.7) | |
| Tumor appearance | 0.07 | |||
| pGGN | 28 (32.2) | 3 (13.0) | 25 (39.1) | |
| mGGN | 42 (48.3) | 14 (60.9) | 28 (43.8) | |
| Solid | 17 (19.5) | 6 (26.1) | 11 (17.2) | |
| Body position | 0.20 | |||
| Left lateral | 33 (37.9) | 7 (30.4) | 26 (40.6) | |
| Right lateral | 22 (25.3) | 4 (17.4) | 18 (28.1) | |
| Supine | 32 (36.8) | 12 (52.2) | 20 (31.3) | |
| Distance from tumor to pleura (mm) | 2 [0, 5] | 2 [0, 3] | 3.5 [0, 6] | 0.051 |
| Tumor location | 0.99 | |||
| Left upper lobe | 30 (34.5) | 8 (34.8) | 22 (34.4) | |
| Left lower lobe | 13 (14.9) | 3 (13.0) | 10 (15.6) | |
| Right upper lobe | 30 (34.5) | 8 (34.8) | 22 (34.4) | |
| Right lower lobe | 14 (16.1) | 4 (17.4) | 10 (15.6) |
Normally distributed continuous variables are presented as mean ± standard deviation, skewed distributed continuous variables are presented as median [25th–75th], and categorized variables are presented as n (%). CABG, coronary artery bypass graft; CAD, coronary heart disease; Co-A, co-ablation; COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; mGGN, mixed ground glass nodule; MWA, microwave ablation; PCI, percutaneous coronary intervention; pGGN, pure ground glass nodule.
Parameters in ablation procedures
We compared the parameters of the ablation procedures between the two groups in Table 3. The number of pleural punctures in the Co-A group was significantly higher than in the MWA group (P<0.001). The probes utilized in the Co-A group were 14-G whereas the MWA antennas used in the MWA group were 17- and 18-G. Additionally, the mean ablation duration was 28.26±7.56 min in the Co-A group and 6.37±2.01 min in the MWA group, respectively (P<0.001). The ablation size between the groups were similar. Needle trajectory path defined as the length of the needle within the lung parenchyma, excluding the chest wall, was also comparable between the two groups.
Table 3. Parameters in ablation procedures.
| Parameters | Group Co-A | Group MWA | P value |
|---|---|---|---|
| Needle trajectory path (mm) | 66 [48, 81] | 62.5 [52, 75] | 0.61 |
| Number of pleural punctures | <0.001 | ||
| 1 | 4 (17.4) | 56 (87.5) | |
| 2 | 17 (73.9) | 8 (12.5) | |
| 3 | 2 (8.7) | 0 (0.0) | |
| Type of ablation device | <0.001 | ||
| 14-G | 23 (100.0) | 0 (0.0) | |
| 17-G | 0 (0.0) | 17 (26.6) | |
| 18-G | 0 (0.0) | 47 (73.4) | |
| Ablation size (longest diameter) (cm) | 4.41±1.12 | 4.34±0.90 | 0.75 |
| Minimum ablation margin (cm) | 0.65±0.28 | 0.57±0.24 | 0.22 |
| The ablation zone touched the pleura | 21 (91.3) | 54 (84.4) | 0.64 |
| The area of pleura ablated (mm2) | 73 [39, 105] | 60.5 [36.5, 101] | 0.90 |
| Ablation duration (min) | 28.26±7.56 | 6.37±2.01 | <0.001 |
Normally distributed continuous variables are presented as mean ± standard deviation, skewed distributed continuous variables are presented as median [25th–75th], and categorized variables are presented as n (%). Co-A, co-ablation; G, gauge; MWA, microwave ablation.
Treatment effectiveness
The median follow-up duration for both the Co-A group and the MWA group was 7 months (range, 5–13 and 6–10 months, respectively, P=0.69). No patients died during the follow-up period. The RFS rate was 95.7% in the Co-A group and 100.0% in the MWA group (P=0.26). One patient in the Co-A group experienced local recurrence 7 months postoperatively and underwent repeat ablation. The median hospital length of stay (HLOS) was 2 days in the Co-A group and 1 day in the MWA group, respectively (P<0.001) (Table 4).
Table 4. Comparison of efficacy between the two groups.
| Parameters | Group Co-A (n=23) | Group MWA (n=64) | P value |
|---|---|---|---|
| HLOS (days) | 2 [1, 16] | 1 [1, 3] | <0.001 |
| Technical success rate (%) | 100.0 | 100.0 | >0.99 |
| Technical efficiency rate (%) | 100.0 | 100.0 | >0.99 |
| Mortality (%) | 0.0 | 0.0 | >0.99 |
| Follow-up period (months) | 7.04±2.01 | 7.27±2.49 | 0.69 |
| RFS rate (%) | 95.7 | 100.0 | 0.26 |
Normally distributed continuous variables are presented as mean ± standard deviation, skewed distributed continuous variables are presented as median [25th–75th], and categorized variables are presented as %. Co-A, co-ablation; HLOS, hospital length of stay; MWA, microwave ablation; RFS, recurrence-free survival.
Adverse events
There were no procedure-related deaths within 30 days of ablation in either group. Complications resulting from the ablation procedures are presented in Table 5. The majority of adverse events were classified as either minor (grade I) or moderate (grade II). Intraoperatively, 31 patients (35.6%) experienced elevated blood pressure, defined as an intraoperative increase of blood pressure exceeding the preoperative baseline by 20 mmHg. Postoperatively, a three-step analgesic protocol was implemented for pain management, with most patients requiring only grade I analgesia. The rate of patients requiring analgesic interventions was significantly higher in the MWA group compared to the Co-A group (45.4% vs. 30.4%, P=0.03). Pneumothorax was the most common complication, occurring in 11 of 23 patients (47.7%) in the Co-A group and 16 of 64 patients (25%) in the MWA group; this difference was not statistically significant (P=0.09). The proportion of pneumothorax cases requiring chest tube placement was significantly higher in the Co-A group (34.8%, 8 of 23 patients) compared to the MWA group (7.8%, 5 of 64 patients) (P=0.008). The incidence of subcutaneous emphysema, pleural effusion, and hemoptysis did not differ significantly between the two groups.
Table 5. Adverse events of the two groups.
| Parameters | All (n=87) | Group Co-A (n=23) | Group MWA (n=64) | P value | CTCAE grade |
|---|---|---|---|---|---|
| Elevated blood pressure | 31 (35.6) | 7 (30.4) | 24 (37.5) | 0.54 | 1 |
| Post-operative analgesics | 0.03 | 2 | |||
| Grade I | 31 (35.6) | 4 (17.4) | 27 (42.2) | ||
| Grade II | 4 (4.6) | 3 (13.0) | 1 (1.6) | ||
| Grade III | 1 (1.1) | 0 (0.0) | 1 (1.6) | ||
| Pneumothorax | 0.09 | ||||
| Mild | 22 (25.3) | 9 (39.1) | 13 (20.3) | ||
| Moderate | 4 (4.6) | 1 (4.3) | 3 (4.7) | ||
| Severe | 1 (1.1) | 1 (4.3) | 0 (0.0) | ||
| Intervention | 0.008 | ||||
| Chest tube drainage | 13 (14.9) | 8 (34.8) | 5 (7.8) | 2 | |
| Observation | 14 (16.1) | 3 (13.0) | 11 (17.2) | 1 | |
| Subcutaneous emphysema (mild) | 5 (5.7) | 3 (13.0) | 2 (3.1) | 0.11 | 1 |
| Pleural effusion (mild) | 5 (5.7) | 2 (8.7) | 3 (4.7) | 0.61 | 1 |
| Transient hemoptysis (mild) | 16 (18.4) | 6 (26.1) | 10 (15.6) | 0.29 | 1 |
| Adverse events 1 month after ablation | |||||
| Delayed pneumothorax | 1 (1.1) | 0 (0.0) | 1 (1.6) | >0.99 | 2 |
| Pleural effusion | 0.57 | ||||
| Mild | 5 (5.7) | 2 (8.7) | 3 (4.7) | 1 | |
| Moderate | 2 (2.3) | 1 (4.3) | 1 (1.6) | 2 | |
| Pneumonia | 2 (2.3) | 1 (4.3) | 1 (1.6) | 0.46 | 2 |
| Fever | 2 (2.3) | 1 (4.3) | 1 (1.6) | 0.46 | 2 |
Categorized variables are presented as n (%). Co-A, co-ablation; CTCAE, Common Terminology Criteria for Adverse Events; MWA, microwave ablation.
Logistic regression model analysis of factors causing pain
We developed univariate and multivariate logistic regression models to investigate the factors causing pain (Table 6). The covariates considered were ablation size, minimum ablation margin, the ablation zone touched the pleura, the area of pleura ablated, ablation duration, and trajectory path length. Univariate and multivariate logistic regression analysis revealed significant correlation between ablation size and pain [odds ratio (OR) =1.778, P=0.04].
Table 6. Univariate and multivariate logistic regression model analysis of factors causing pain.
| Parameters | Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | ||
| Ablation size (longest diameter) (cm) | 1.691 (1.037–2.758) | 0.035 | 1.778 (1.038–3.046) | 0.04 | |
| Minimum ablation margin (cm) | 0.679 (0.121–3.795) | 0.66 | – | – | |
| The ablation zone touched the pleura | 1.488 (0.412–5.377) | 0.54 | – | – | |
| The area of pleura ablated (mm2) | 1.002 (0.992–1.012) | 0.68 | – | – | |
| Ablation duration (min) | 0.988 (0.948–1.030) | 0.58 | – | – | |
| Trajectory path length (mm) | 1.020 (0.996–1.045) | 0.10 | – | – | |
CI, confidence interval; OR, odds ratio.
Discussion
Image-guided thermal ablation (IGTA) represents a minimally invasive therapeutic modality that leverages the biological effects of heat or cold to induce direct, irreversible damage or necrosis of tumor cells within a target organ. It serves as a viable alternative for patients with unresectable early-stage NSCLC. IGTA encompasses techniques such as RFA, MWA, and CA (8). MWA utilizes high-frequency electromagnetic waves to generate thermal energy. This technique employs frequencies of either 915 or 2,450 MHz to create a microwave electromagnetic field, which induces rapid oscillation of polar molecules within tissues. This, in turn, leads to an increase in kinetic energy, triggering a cascade of molecular collisions and friction, ultimately resulting in a substantial elevation of temperature (4). Based on the Phase-Transition principle, Co-A induces tumor cell necrosis and apoptosis through several mechanisms. These include mechanical disruption of the cell membrane and organelles following the formation of intracellular ice crystals at ultra-low temperatures, leading to the release of intracellular contents (9). These released contents can activate an anti-tumor immune response and contribute to tumor cell destruction (10). Additionally, Co-A not only damages tumor blood vessels but also causes intravascular embolism, resulting in the interruption of tumor microcirculation (4). Since the introduction of Co-A in China, it was gradually applied to solid tumors of various systems and accepted by clinicians. However, the optimal selection of ablation methods to maximize clinical benefit for patients, as well as comprehensive comparative studies on the safety and efficacy of Co-A vs. MWA specifically for subpleural NSCLC, remain limited.
In contrast to MWA, CA allows for visualization of ice ball formation under CT guidance, thus clearly delineating the ablation boundary (11). Furthermore, large airways, blood vessels, the diaphragm, and other organ structures exhibit greater tolerance to cold temperatures than to heat (6). CA also demonstrates a more pronounced immune activation effect compared to MWA or RFA (12,13). Intraoperatively, CA provides an analgesic effect and is generally well-tolerated by patients. In clinical applications, due to its high heat generation efficiency and lack of susceptibility to heat-sink effect, MWA poses a relatively higher risk for lung nodules adjacent to the heart and major blood vessels. In contrast, the low-density ice ball formation of Co-A can be monitored through dynamic CT scanning, making it relatively safer for lung nodules adjacent to the heart and major blood vessels. However, CA is associated with a higher number of pleural punctures, potentially increasing the risk of pneumothorax (14). Moreover, the risk of bleeding is increased with CA due to the longer procedure duration and platelet consumption (4).
The findings of our study demonstrated that the mean procedure time for Co-A was significantly longer than that for MWA (P<0.001). This difference is attributable to the necessity of performing “freezing-thawing” cycles during Co-A procedures. Due to the retrospective design of our study, we were unable to compare visual analog scale (VAS) scores perioperatively. Consequently, our analysis was limited to the postoperative utilization of analgesic medications according to the three-step analgesic ladder for pain management. The rate of postoperative analgesic medication use was significantly lower in the Co-A group compared to the MWA group [7 patients (30.4%) vs. 29 patients (45.4%), P=0.03]. We compared the ablation size between the two groups and no statistical difference was observed. Univariate and multivariate logistic regression analysis revealed significant correlation between ablation size and pain (OR =1.778, P=0.04). Thus, the differences in pain may be related to the ablation protocols themselves.
Additionally, we acknowledge that the lower analgesic intervention in the Co-A group does not necessarily equate to less pain, as analgesic use can be influenced by various factors, such as doctors’ prescribing habits, patients’ tolerance, and patients’ compliance. Pain associated with MWA performed under local anesthesia is likely attributable to the stimulation of pleural nerves by thermal conduction (15). General anesthesia, intercostal nerve blocks, pleural infiltration anesthesia, artificial pleural effusion, and artificial pneumothorax have been utilized to mitigate pain during ablation procedures (15-18). While these techniques can provide some degree of analgesia, several limitations persist. General anesthesia may not be suitable for elderly patients with coexisting cardiorespiratory insufficiency. Intercostal nerve blocks require coordination with the anesthesiology department. Pleural infiltration anesthesia is limited when the lesion is adjacent to both pleural and bony structures. Furthermore, artificial pneumothorax and pleural effusion may be contraindicated in patients with pulmonary adhesions resulting from prior surgical resection or radiotherapy, as well as in cases of severe respiratory insufficiency. Moreover, excessive compression of lung parenchyma may increase the risk of complications such as pleural fistulas, respiratory distress, and subcutaneous emphysema following thermal ablation (16,19). Therefore, Co-A may represent a more appropriate therapeutic option when the tumor is in close proximity to the pleura (20).
Concerning efficacy, a meta-analysis reported that the 1-, 2-, 3-, and 5-year overall survival (OS) rates for MWA in the treatment of stage I NSCLC were 92%, 88%, 66%, and 36%, respectively. The corresponding 1-, 2-, 3-, and 5-year disease-free survival (DFS) rates following the procedure were 88%, 58%, 65%, and 41%, respectively (21). In another multicenter study examining the long-term follow-up results of MWA in patients ineligible for surgery, Ni et al. reported that, with a median follow-up of 54.8 months, the 1-, 3-, and 5-year DFS rates were 89.5%, 49.4%, and 42.7%, respectively. The corresponding 1-, 3-, and 5-year OS rates were 99%, 75.6%, and 54.1%, respectively (2). With respect to CA for stage I NSCLC, Moore et al. reported local control in 40 of 45 patients with stage I NSCLC (89%), with a mean follow-up period of 51 months. The 5-year OS rate was 67.8%±15.3% and the 5-year progression-free survival (PFS) rate was 87.9%±9.0% (22). Yamauchi et al. reported RFS in 15 of 22 patients with stage I NSCLC (68%), with a median follow-up period of 23 months (23).
Given that our center introduced Co-A equipment in August 2023, the mean follow-up duration for this study is limited to 7 months. During this follow-up period, only one patient in the Co-A group required repeat ablation due to local recurrence. The initial complete ablation rates, local recurrence rates, and survival rates for both ablation methods were comparable to those reported in prior studies, with no statistically significant differences observed. While long-term prognostic outcomes are still being monitored, these preliminary findings offer a valuable reference for clinical practice.
Regarding complications, the most frequently reported adverse events associated with Co-A and MWA for NSCLC include pneumothorax, pleural effusion, and hemoptysis. In this study, the incidence of pneumothorax, hemorrhage, and pleural effusion were 47.7%, 26.1%, and 8.7% in the Co-A group, and 25%, 15.6%, and 4.7% in the MWA group, respectively (all P>0.05), which is consistent with previous reports (18,24-26). However, the rate of pneumothorax requiring chest tube drainage was significantly higher in the Co-A group (34.8%) compared to the MWA group (7.8%) (P=0.008). We hypothesize that this disparity may be attributable to the larger diameter of the co-probes compared to the MWA antennas and the longer procedure duration associated with Co-A. Furthermore, the greater number of pleural punctures during Co-A, which can increase the risk of pneumothorax, may also contribute to this difference. Conversely, the coaxial technique and embolization of the needle tract, frequently employed in MWA, were not used in Co-A (27).
We would recommend the following procedural modifications to mitigate the risk of pneumothorax in future applications of Co-A: employing a more meticulous puncture technique to minimize lung injury with the guidance of puncture navigation devices, using smaller Co-A probes, and applying artificial pneumothorax or artificial pleural effusion technique for tumors near the pleura. Although Co-A may result in platelet consumption, the risk of bleeding was not significantly increased in our study, potentially due to the hemostatic effects of coagulation during the thawing phase.
As a retrospective study, there may be inherent selection biases influencing which patients received Co-A vs. MWA. The present study is limited by its retrospective, single-center design and a modest sample size. Moreover, the Co-A group is notably smaller than the MWA group, which may affect the statistical power of comparisons. Additional limitations include a relatively short median follow-up period and the absence of a comparative VAS assessment between the two groups. Assessment of OS and PFS would benefit from a longer period. We acknowledge that our relatively short follow-up could potentially misrepresent long-term efficacy. We would like to emphasize that this study represents an early, exploratory analysis of this technique. As such the primary goal was to evaluate safety and technical feasibility. To address this, we will plan a prospective study with a longer follow-up period, more balanced sample sizes, and standardized pain evaluation protocol.
Conclusions
Co-A and MWA are commonly employed ablation techniques for cancer treatment. Both ablative modalities present unique advantages and disadvantages. The selection and application of these techniques should be determined based on tumor location, risk of complications, patient comorbidities, and the expertise of the interventional radiologist. In conclusion, our findings indicate that Co-A for subpleural stage I NSCLC demonstrates comparable safety and efficacy to MWA, with a lower incidence of intraoperative pain and good patient tolerance. While the rate of pneumothorax requiring chest tube drainage is higher with Co-A than with MWA, it remains within an acceptable range. To draw more reliable conclusions about long-term prognosis, a prospective study with long-term follow-up is essential.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The medical research ethics committee of Beijing Hospital approved the study (No. 2024BJYYEC-KY021-01), and the requirement for informed consent was waived due to the retrospective nature of this study.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-296/rc
Funding: The work was supported by the Clinical and Translational Medical Research Fund of the Chinese Academy of Medical Sciences (to X.L.) (No. 2023-I2M-C&T-A-013) and the National Key R&D Program of China under Grant (to Z.B.) (Nos. 2023YFC2414000 and 2023YFC2414003).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-296/coif). Z.B. received funding from the National Key R&D Program of China (Nos. 2023YFC2414000 and 2023YFC2414003). X.L. received funding from the Clinical and Translational Medical Research Fund of the Chinese Academy of Medical Sciences (No. 2023-I2M-C&T-A-013). The other authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-296/dss
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