CT-guided ablation for stage I non-small cell lung cancer: a comparative study between cryoablation and microwave ablation

Abstract

Background

Computed tomography (CT)-guided tumor ablation has emerged as an important treatment option for patients with stage I non-small-cell lung cancer (NSCLC) who are poor surgical candidates. Here, the clinical performance and safety profiles of cryoablation (CA) and microwave ablation (MWA) for stage I NSCLC were compared.

Methods

Consecutive patients with stage I NSCLC treated with CT-guided CA or MWA between November 2022 and March 2025 were retrospectively enrolled. Outcomes evaluated included ablation effectiveness, long-term survival, and procedure-related complications, which were examined and compared between groups.

Results

Ninety-one patients were eligible for analysis in the present study, of whom 48 underwent CA and 43 underwent MWA. Baseline characteristics did not differ significantly between groups. Primary complete ablation rates were 93.8% for CA and 95.3% for MWA (p = 1.000); secondary complete ablation was achieved in all remaining cases in both cohorts. Patients treated with CA reported significantly lower procedural pain scores than those treated with MWA (median 1 vs. 3, p < 0.001). Median postoperative hospital stay was comparable (3 vs. 2 days, p = 0.376). Median progression-free survival (PFS) was 16 months for CA and 15 months for MWA (p = 0.763), while median overall survival (OS) was 23 and 24 months, respectively (p = 0.894). Complication rates were similar in both groups.

Conclusions

For stage I NSCLC, both CA and MWA demonstrated comparable therapeutic efficacy and safety. However, CA offered the advantage of reduced intraprocedural pain compared with MWA.

Introduction

Lung cancer is still the deadliest cancer globally and has the highest morbidity rate [1]. NSCLC constitutes approximately 75%-85% of lung cancer cases [2]. With the increasing implementation of chest CT screening, more stage I NSCLC cases are being detected, presenting an opportunity for curative resection and favorable long-term survival [3].

For operable stage I NSCLC patients, lobectomy combined with hilar and mediastinal lymph node dissection remains the standard treatment, yielding 5-year survival rates of 57%-85% [2]. Moreover, recent studies suggest that sublobar resection may provide similar survival outcomes to lobectomy for tumors ≤ 2 cm [3, 4]. Despite these advances, an estimated 20% of stage I NSCLC patients are unable to undergo surgery due to comorbidities or limited cardiopulmonary reserve [5]. CT-guided ablation has therefore become an accepted nonsurgical alternative for this subset of patients [6]. Although ablation may result in higher local recurrence rates and shorter progression-free survival (PFS) and overall survival (OS) than sublobectomy, it remains a viable treatment for patients who are not suitable candidates to undergo surgical management [6].

Radiofrequency ablation (RFA), CA, and MWA have all been recognized as effective ablative strategies in early-stage NSCLC [6, 7]. RFA and MWA achieve tumor destruction via thermal energy, with MWA offering advantages such as a larger and more uniform ablation zone and reduced heat-sink effect compared to RFA [8]. CA, in contrast, induces cellular damage by freezing tissue and is known to cause less procedural pain than heat-based modalities [9]. However, direct comparisons between CA and MWA in stage I NSCLC remain limited.

This study aimed to compare the safety and effectiveness of CA versus MWA in patients with stage I NSCLC.

Methods

Study design

The institutional review boards of The First Affiliated Hospital of Ningbo University and Xuzhou Central Hospital gave approval for this retrospective study. Due to its retrospective nature, informed consent requirements were waived.

Patients who underwent CT-guided CA or MWA for stage I NSCLC between November 2022 and March 2025 were reviewed. Inclusion criteria were: (a) histologically confirmed NSCLC; (b) stage I disease according to TNM classification; (c) deemed unsuitable for surgery; and (d) no prior NSCLC-directed therapy. Exclusion criteria included: (a) Eastern Clinical Oncology Group performance status (ECOG PS) >2; (b) tumors adjacent to major cardiac structures or large vessels; (c) history of other malignancies; or (d) significant dysfunction of cardiac, pulmonary, hepatic, renal, or coagulation systems.

In this study, all patients could undergo both MWA and CA. Before treatment, we have introduced the details of advantages and disadvantages of both techniques to each patient. For example, the advantages of MWA mainly include short procedural time and low cost, while the main disadvantage is high level of intraoperative pain. The advantages of CA mainly include precise ablation and low level of intraoperative pain, while the disadvantages of CA mainly include long procedural time and high cost. All patients decided to choose one of the 2 methods after considering the advantages and disadvantages mentioned above and discussing with their families.

CT-guided ablation

All procedures were performed under CT guidance with local anesthesia by experienced thoracic interventional radiologists (>5 years). Patient positioning varied according to tumor location.

For CA, an argon-helium system (CryoHit, Galil Medical, Israel) was used. The number and placement of cryoprobes were determined based on tumor size, shape, and location. Each lesion underwent two freeze-thaw cycles (10-minute freeze, 3-minute thaw). Tip temperatures reached approximately −140 °C via rapid argon expansion, followed by helium-mediated displacement of the argon to initiate thawing.

MWA was performed using the KY-2450B generator (Kangyou, Nanjing, China; frequency 2450 ± 50 MHz). Antenna placement followed the same principles as was used for CA. A water-cooled antenna was used, with energy settings of 40–50 W for 5–10 minutes.

After ablation procedures had been completed, CT was repeated to confirm adequate ablation margins (5–10 mm beyond tumor borders) and to identify procedure-related complications.

Follow-up

Patients were evaluated at 1, 3, and 6 months post-procedure and every 6 months thereafter. Assessments included imaging and physical examinations. Follow-up continued until death or study termination (September 2025). Additional cancer-directed therapy after ablation was permitted. The decision and protocol of additional chemotherapy, target therapy, or immunotherapy was made and individually designed based on the preoperative pathological, immunohistochemical, and molecular tests.

Definition

Complete ablation was defined as the absence of enhancement on contrast-enhanced CT one week post-procedure [9]. If incomplete, repeat ablation was performed. Pain was assessed using a visual analog scale (VAS, 0–10). Local progression was defined as tumor enlargement or new enhancement within the ablation zone [2, 9]. PFS was calculated from the ablation date to the time of progression. OS was calculated from the time of ablation until death or last follow-up.

Statistical analyses

Continuous variables were reported as mean ± standard deviation or median (interquartile range). Between-group comparisons used independent-samples t-tests or Mann-Whitney U tests. Categorical variables were assessed using chi-square or Fisher’s exact tests. Prognostic factors for PFS and OS were evaluated using Cox regression. Statistical significance was set at p < 0.05. Analyses were performed using SPSS 16.0.

Results

Patients

A total of 91 patients met the inclusion criteria and were enrolled in the study analyses, with 48 having undergone CA (Fig. 1) and 43 having undergone MWA (Fig. 2). Baseline demographic and tumor characteristics did not significantly differ between groups (Table 1). Seven patients (MWA group: 3, CA group: 4) had the mixed ground glass capacity lesion aspect on CT (p = 1.000). Post-procedure anticancer therapy was administered to 18 patients in the CA cohort and 17 in the MWA cohort.

Fig. 1.

The procedures of CT-guided CA for stage I NSCLC. (a) The chest CT showed the lesion located at the right upper lobe. (b) The image of CT-guided CA. (c) The repeat CT showed that the ablation area completely covered the lesion

Fig. 2.

The procedures of CT-guided MWA for stage I NSCLC. (a) The chest CT showed the lesion located at the right upper lobe. (b) The image of CT-guided MWA. (c) The repeat CT showed that the ablation area completely covered the lesion

Table 1.

Baseline data of the patients

	CA group	MWA group	P value
Patients number	48	43
Age (y)	74.1 ± 8.9	73.3 ± 8.6	0.666
Gender			0.517
Male	30	24
Female	18	19
ECOG PS	1 (Q1: 0; Q3: 1)	1 (Q1: 0; Q3: 1)	0.259
Pathological diagnoses			0.992
Adenocarcinoma	32	29
Squamous cell carcinoma	10	9
Others	6	5
Clinical stage			0.184
IA (T1N0M0)	29	20
IB (T2aN0M0)	19	23
Tumor size (mm)	25.7 ± 12.4	24.1 ± 11.1	0.528
Lung sides			0.657
Left	19	19
Right	29	24
Lobe			0.836
Upper	28	26
Non-upper	20	17
Postoperative anticancer treatments (total)	18	17	0.842
Chemotherapy	9	10
Target therapy	11	8
Immunotherapy	10	11

CA: cryoablation; ECOG PS: Eastern Clinical Oncology Group performance status; MWA: microwave ablation

Treatment outcomes

Initial technical success was high in both groups, with primary complete ablation rates of 93.8% forCA and 95.3% for MWA (p = 1.000). All patients who did not achieve primary ablation attained complete ablation after a second procedure (100% in both cohorts; Table 2). Pain scores were significantly lower following CA compared with MWA (median 1 vs. 3, p < 0.001). Length of postoperative hospitalization was similar (median 3 vs. 2 days, p = 0.376).

Table 2.

Treatment outcomes

	CA group	MWA group	P value
Primary complete ablation	45 (93.8%)	41 (95.3%)	1.000
Secondary complete ablation	48 (100%)	43 (100%)	Not applicable
Pain score	1 (Q1: 1; Q3: 2)	3 (Q1: 3; Q3: 3)	<0.001
Postoperative hospital stay (d)	3 (Q1: 2; Q3: 4)	2 (Q1: 2; Q3: 4)	0.376
Tumor progression
Local	13 (27.1%)	12 (27.9%)	0.93
Distant	10 (20.8%)	11 (25.6%)	0.591
Death	10 (20.8%)	9 (20.9%)	0.991
PFS (months)	16	15	0.763
OS (months)	23	24	0.894

CA: cryoablation; PFS: progression-free survival; MWA: microwave ablation; OS: overall survival

During follow-up, 23 patients (47.9%) in the CA group and 23 (53.5%) in the MWA group experienced tumor progression (Table 2). One- and two-year PFS rates were 46.7% and 43.1% in the CA group, and 44.8% and 41.1% in the MWA group, respectively. Median PFS was comparable (16 vs. 15 months, p = 0.763; Fig. 3a).

Fig. 3.

The (a) PFS and (b) OS between CA and MWA in the entire patients

Ten patients in the CA cohort and nine in the MWA cohort died during follow-up. One- and two-year OS rates were 79.2% and 68.7% for CA and 76.9% and 71.4% for MWA. Median OS did not significantly differ (23 vs. 24 months, p = 0.894; Fig. 3b).

Cox regression analysis identified clinical stage IB disease as an independent predictor of worse PFS (p = 0.01) and OS (p < 0.001) (Tables 3 and 4).

Table 3.

Cox-regression analysis for PFS

	Univariate analysis			Multivariate analysis
	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age	0.993	0.961–1.026	0.684
Gender
Male	1
Female	0.650	0.356–1.185	0.160
ECOG PS	1.393	0.933 - 2.079	0.105
Tumor stage
IA (T1N0M0)	1			1
IB (T2aN0M0)	3.224	1.771–5.870	<0.001	2.347	1.232–4.472	0.01
Pathological diagnoses
Non-adenocarcinoma	1			1
Adenocarcinoma	0.496	0.276–0.891	0.019	0.823	0.439–1.543	0.544
Lung side
Right	1
Left	0.843	0.462–1.536	0.576
Lobe
Non-upper	1
Upper	0.828	0.463–1.480	0.524
Ablation methods
CA	1
MWA	1.089	0.611–1.941	0.773
Postoperative anticancer treatments
No	1			1
Yes	2.807	1.540–5.115	0.001	1.922	0.982–3.759	0.056

CA: cryoablation; PFS: progression-free survival; MWA: microwave ablation

Table 4.

Cox-regression analysis for OS

	Univariate analysis			Multivariate analysis
	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age	1.054	0.993–1.119	0.083	1.023	0.950–1.101	0.543
Gender
Male	1
Female	0.586	0.223–1.545	0.280
ECOG PS	2.253	1.185 - 4.286	0.013	1.758	0.830–3.724	0.141
Tumor stage
IA (T1N0M0)	1			1
IB (T2aN0M0)	7.780	2.756–21.958	<0.001	6.972	2.470–19.682	<0.001
Pathological diagnoses
Non-adenocarcinoma	1
Adenocarcinoma	1.391	0.500–3.869	0.527
Lung side
Right	1
Left	1.277	0.511–3.193	0.601
Lobe
Non-upper	1
Upper	0.797	0.323–1.964	0.622
Ablation methods
CA	1
MWA	0.941	0.382–2.319	0.895
Postoperative anticancer treatments
No	1
Yes	1.960	0.788–4.875	0.148

CA: cryoablation; MWA: microwave ablation; OS: overall survival

Complications

Complication profiles were similar across both treatment modalities (Table 5). Rates of pneumothorax (43.8% vs. 41.9%, p = 0.856), hemoptysis (12.5% vs. 11.6%, p = 0.899), and pulmonary infection (4.2% vs. 2.3%, p = 1.000) did not differ significantly. Chest tube drainage was required in six CA patients and seven MWA patients, while others were managed conservatively.

Table 5.

Treatment -related complications

	CA group	MWA group	P value
Pneumothorax	21 (43.8%)	18 (41.9%)	0.856
Hemoptysis	6 (12.5%)	5 (11.6%)	0.899
Lung infection	2 (4.2%)	1 (2.3%)	1.000

CA: cryoablation; MWA: microwave ablation

Subgroup analyses

Subgroup analyses stratified by disease stage (IA vs. IB) demonstrated similar outcomes between the two treatments.

For Stage IA patients, PFS at 1 and 2 years was 60.9% in the CA cohort and 55.0% in the MWA cohort, with median PFS of 20 and 19 months (p = 0.593; Fig. 4a). OS at 1 and 2 years was 96.6% and 91.2% for CA versus 96.4% and 86.8% for MWA, with median OS of 28 vs. 27 months (p = 0.683; Fig. 4b).

Fig. 4.

The (a) PFS and (b) OS between CA and MWA in the patients with stage IA NSCLC

For Stage IB patients, 1-year PFS rates were 19.3% for CA and 22.0% for MWA, with both groups reaching 0% by year 2; median PFS was 6 months for both (p = 0.990; Fig. 5a). One- and two-year OS rates were 68.5% and 22.8% (CA) versus 50.0% and 25.0% (MWA), with median OS of 13 vs. 14 months (p = 0.906; Fig. 5b).

Fig. 5.

The (a) PFS and (b) OS between CA and MWA in the patients with stage IB NSCLC

Discussion

Sublobectomy and percutaneous ablation are both utilized in the management of stage I NSCLC [6]. Evidence from a prior meta-analysis demonstrated that sublobectomy offers a markedly lower incidence of local recurrence compared with ablation (5.0% vs. 25.4%, p < 0.0001), along with significantly prolonged OS and PFS [6]. However, percutaneous ablation remains a valuable treatment option for patients who are medically ineligible for surgery [6]. In contrast to sublobectomy, ablation can be completed under local anesthesia and is associated with a shorter postoperative hospitalization period [6].

We evaluated the comparative clinical performance and safety profiles of CA and MWA in patients with stage I NSCLC. CA and MWA employ distinct mechanisms in the form of cryogenic tissue destruction versus thermal coagulation. Both modalities demonstrated high efficacy, with nearly identical primary complete ablation rates (93.8% vs. 95.3%, p = 1.000) and universal secondary complete ablation success. Comparable short-term tumor responses between these two techniques have also been reported by Li et al. [10], and similar findings in hepatocellular carcinoma suggest that CA and MWA may achieve equivalent ablative outcomes across malignancies [11].

In addition, pain severity differed substantially between modalities. Patients undergoing CA reported significantly less postoperative discomfort than those treated with MWA, likely due to CA’s intrinsic anesthetic effect via tissue freezing [6]. Li et al. [10] similarly observed lower intraprocedural pain in the CA cohort (3 vs. 5, p < 0.001). Postoperative length of stay did not vary significantly, suggesting that the choice of ablation method does not meaningfully affect recovery duration.

Tumor progression served as a main clinical endpoint. Rates of local (27.1% vs. 27.9%, p = 0.93) and distant (20.8% vs. 25.6%, p = 0.591) disease recurrence were statistically comparable between CA and MWA groups. These values are consistent with those reported in a meta-analysis evaluating ablation outcomes for stage I NSCLC [6]. Likewise, PFS, OS, and 1- and 2-year survival estimates showed no significant differences. The PFS observed here aligns with previously published data on MWA for stage I disease [2]. Nan et al. [12] reported 2-year OS rates of 66.0% and 69.9% following CA and MWA, respectively, which were slightly lower than those in our study, likely due to their inclusion of patients across all NSCLC stages, whereas our sample was limited to stage I tumors.

Cox regression analysis identified stage IB disease as the only independent predictor of reduced PFS and OS. Stratified subgroup evaluation further confirmed that survival outcomes did not differ between CA and MWA within either stage IA or stage IB cohorts. Thus, tumor stage rather than ablation modality appears to be the primary determinant of long-term prognosis.

Both treatment groups demonstrated similar complication profiles, with comparable rates of pneumothorax, hemoptysis, and infection. These findings align with those of Li et al. [10], supporting the notion that CA and MWA offer comparable safety for pulmonary tumor ablation.

This study has certain limitations of note. Firstly, the retrospective design introduces unavoidable selection bias, although baseline characteristics were well balanced between groups. Secondly, operator experience varied between the two participating centers, which may have influenced outcomes. Finally, the sample size was modest, underscoring the need for prospective, randomized studies with larger populations to validate these results.

Conclusion

In summary, both CA and MWA provided equivalent therapeutic efficacy and safety in stage I NSCLC. While oncologic outcomes did not differ between techniques, CA was associated with significantly less procedural pain. Additional prospective clinical trials are warranted to further refine patient selection and confirm these findings.

Abbreviations

CA

Cryoablation

CT

Computed tomography

ECOG PS

Eastern Clinical Oncology Group performance status

MWA

Microwave ablation

NSCLC

Non-small-cell lung cancer

OS

Overall survival

PFS

Progression-free survival

RFA

Radiofrequency ablation

Author contributions

YL and ZY designed this work. JL, FT, and HW collected the clinical data. JH performed the statistical analyses. RH wrote this article. Final manuscript was approved by all authors.

Funding

None.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was approved by Ethics Committee of The First Affiliated Hospital of Ningbo University and Xuzhou Central Hospital. All methods were carried out in accordance with the 1964 Declaration of Helsinki. All patients provided the consent to participate.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.