Surgical Outcomes of Video‐Assisted Thoracic Surgery Combined With Computed Tomography‐Guided Microwave Ablation for Lung Cancer Presenting as Multiple Ground‐Glass Opacities: A 5‐Year Retrospective Cohort Study

ABSTRACT

Background

Multiple ground glass opacities (mGGOs) are frequently observed in patients with early‐stage lung adenocarcinoma. The most appropriate and effective treatment for these mGGOs remains controversial. The purpose of this study was to retrospectively review the usefulness and safety of performing video‐assisted thoracic surgery (VATS) combined with computed tomography (CT)‐guided microwave ablation (MWA) in patients with synchronous multiple primary lung cancer (sMPLC) and to demonstrate the long‐term surgical outcomes at our institute.

Materials and Methods

From April 2019 to December 2021, we enrolled 47 patients who underwent VATS combined with CT‐guided MWA for mGGOs. Comprehensive data regarding the enrolled subjects, including clinical features, imaging findings, histopathological characteristics, and surgical records, were meticulously extracted from the surgical database and electronic medical records. The outcomes assessed in this study included the feasibility and safety profile of the combined procedure, as well as event‐free survival (EFS), local progression‐free survival (LPFS), and overall survival (OS).

Results

A total of 47 patients with sMPLC characterized by mGGOs underwent VATS combined with CT‐guided MWA. In this cohort, 173 GGOs were removed, including 69 nodules (39.9%) larger than 8 mm and 104 nodules (60.1%) measuring between 5 and 8 mm. We recorded all 58 types of VATS surgeries performed on 83 nodules. Additionally, 90 secondary nodules were treated with CT‐guided MWA during either a single hospitalization or multiple hospitalizations (ranging from 1 to 4). We achieved a 100% technical success rate among the 47 patients. During the follow‐up, there was no local tumor progression or recurrence among the 47 patients. Event‐free survival was 100% at 3 years and 66.82% at 5 years, and the 5‐year overall survival rate was 97.5%, with only one patient dying from an unrelated cause.

Conclusion

VATS combined with CT‐guided MWA is a safe and effective method for patients with mGGOs. This combination marks the onset of an era where surgeons can utilize both a needle and a scalpel simultaneously.

VATS combined with CT‐guided MWA is a safe and effective treatment option for patients with mGGOs. This hybrid surgical approach has broadened the treatment options available to thoracic surgeons and enhanced their procedural capabilities, marking an era in which surgeons can simultaneously use a needle and scalpel.

1. Introduction

Ground‐glass opacity (GGO) is a radiological finding on high‐resolution computed tomography (HRCT) of the lungs and is characterized by a hazy, increased opacity without obscuring the underlying bronchial structures or pulmonary vessels [1, 2]. Advances in high‐resolution computed tomography (HR‐CT) and the application of low‐dose spiral computed tomography (CT) in lung cancer screening have resulted in the detection of multiple GGOs (mGGOs), leading to an increase in their diagnosis in clinical practice [3, 4]. Previous research has indicated that the presence of mGGOs is often associated with multifocal adenocarcinomas, which have also been identified as synchronous multiple primary lung cancers (sMPLCs) [5]. However, the natural history of sMPLC and the molecular differences between isolated mGGOs and mGGOs have not been thoroughly investigated. Therefore, selecting appropriate interventions for these patients remains controversial [6, 7]. Surgical resection, particularly video‐assisted thoracoscopic surgery (VATS), is the preferred treatment for sMPLC [8, 9, 10]. However, the dispersal of mGGOs across multiple lobes, with more than three bilateral lesions, presents a significant challenge for thoracic surgeons. The most significant barrier to optimal treatment for patients with mGGOs is the difficulty in obtaining an exact pathological diagnosis for each nodule [11, 12, 13]. The pathological characteristics of both primary and secondary lesions significantly influence patient survival [14, 15, 16]. As a result, effective treatment is imperative for patients with sMPLC, particularly for those who are unsuitable or unwilling to undergo an additional operation. Microwave ablation (MWA) has recently become a prevalent, novel, and localized treatment option for pure GGOs (pGGOs) and other metastatic lesions in patients who cannot undergo surgery [14, 15]. Accordingly, thoracoscopic resection of primary lesions combined with CT‐guided MWA of multiple micronodules is an alternative method for thoracic surgeons to treat sMPLC. This study collected clinical and pathological data and 5‐year outcomes for all patients who underwent VATS combined with CT‐guided MWA. Compared with a previous study [16], this study is the first to report the long‐term image prognosis of VATS combined with CT‐guided MWA in sMPLC patients in a larger cohort.

2. Materials and Methods

2.1. Study Design

The present study was a single‐center retrospective analysis using a subset of a prospective database of consecutively enrolled patients who received multimodality treatment for GGOs from April 2019 to December 2021 (ChiCTR×××××).

The following information was collected and recorded: general information and clinical features, including imaging, histopathology, and surgical records.

The inclusion criteria were as follows: adults aged ≥ 18 years; having one or more residual malignant ground‐glass nodules (< 2 cm) whose malignancy was confirmed by a multidisciplinary team consisting of a radiologist, a pathologist, and a thoracic surgeon; having good general condition; having a performance score of 0–1 (status assessment by the Eastern Cooperative Oncology Group (ECOG)); and being free of severe comorbidities involving the heart, liver, kidney, and other important organs. All patients with sMPLC were treated via VATS combined with CT‐guided MWA. The work has been reported in line with the Standards for Quality Improvement Reporting Excellence (SQUIRE) criteria [17].

2.2. CT Scanning Program and Parameters

All lung MWA procedures were performed via CT guidance (Somatom Sensation 64; Siemens, Erlangen, Germany) with the following parameters: 5‐mm collimation, 30 mAs, 120 kV, and 5‐mm section thickness. The microwave system comprised an ECO‐100A MWA delivery system (ECO Medical Instruments Co. Ltd. Nanjing, China; CFDA Certificate No. 20173251268) and a cooled‐shaft antenna (ECO‐100AI13) made of composite metal materials.

2.3. Patients and Procedures

Initially, 62 patients with complete clinical data who underwent VATS combined with CT‐guided MWA were screened. Among these patients, 10 were excluded because they were lost to follow‐up, and five were changed to receive immunotherapy after surgery. Finally, 47 patients were included in the analysis (Figure 1). All surgeries in this study were performed by the same experienced thoracic surgeon at our institution.

FIGURE 1.

Screening process for eligible patients.

2.4. VATS and CT‐Guided MWA Strategy and Technique

A thin‐section HRCT scan was performed by an experienced radiologist following the American Joint Commission on Cancer (AJCC) 8th edition for non‐small cell lung cancer (NSCLC) to determine the parameters of GGOs and make a definitive diagnosis. The size and location of the tumors and the patient's general condition should be carefully evaluated before the surgical approach is selected. On the basis of the patient's overall condition, we first selected thoracoscopic surgery, usually initiating the first microwave ablation therapy 3–5 days after surgery. Since the patient had mGGOs, we could perform up to four ablation sessions after surgery during multiple hospitalizations (1–4).

GGOs exhibiting two or more features are considered primary lesions: spiculation, lobulation, pleural retraction, air bronchogram, vacuole sign, and a consolidation diameter‐to‐tumor diameter ratio (CTR) exceeding 50%. On the basis of imaging findings, GGOs that meet the criteria for dominant lesions are highly suspected to be invasive adenocarcinomas [18, 19, 20]. A multidisciplinary team (MDT) primarily determines the extent of resection of primary lesions by balancing the risks and benefits of the surgery. Sublobar resection, which includes segmentectomy or wedge resection, is the primary treatment option. When there are multiple dominant lesions, anatomical resection of the first lesion, followed by limited resection of the second lesion, may be a safer and more beneficial option for synchronous bilateral lesions. We determined whether to modify the surgical plan on the basis of intraoperative frozen section pathology. The specimen was removed, and the presence of the lesion was confirmed before histopathological examination. A chest tube was placed, and the patient recovered and was sent to the thoracic surgical ward for observation.

Lesions with a CTR of < 0.5 were considered GGO‐predominant tumors. CT‐guided MWA was performed for secondary lesions, such as pGGOs and GGO‐predominant mGGOs. Typically, MWA therapy for secondary lesions is performed 3–5 days after VATS. The procedure was performed in the interventional radiology room. An ECO‐100A1 MWA system and a 14‐ or 16‐gauge cooled‐shaft antenna were used for MWA. The power was set between 50 and 70 W. Satisfactory anesthesia was achieved via a 1% lidocaine solution.

The patient was placed in the appropriate position. A skin marker was used to determine the needle insertion site. A CT scan was performed to determine the puncture point, angle, depth of the needle (target skin distance), and relationship between the tumor and surrounding structures. We used core‐needle biopsy (CNB) via a coaxial cannula to obtain pathological samples during ablation needle puncture. The scans were repeated until the ablation needle reached the center of the tumor. After the ablation needle was placed, two 6–8 min ablation cycles were typically performed to achieve a “postablation target zone (PTZ)”, which was generally 0.5–1.0 cm larger than the tumor site. Track ablation was performed at 20 W to avoid implantation metastasis in the needle pathway. A chest X‐ray or CT scan was performed after 24–48 h to evaluate complications. Conservative treatment was adopted if the patient developed a small asymptomatic pneumothorax or pleural effusion without significant complications (Figure 2).

FIGURE 2.

Images of the VATS Combined with CT‐Guided Microwave Ablation procedure and follow‐up in 43‐year‐old woman with synchronous multiple primary lung cancers. (A) In May 2019, preoperative three‐dimensional computed tomography reconstruction suggested that the patient had multiple nodules in both pulmonary lobes. (B) On May 11, 2019, the patient underwent a right lung wedge resection of the major nodules, and on August 17, 2019, the patient underwent a left lung wedge resection of the nodules. Postoperative three‐dimensional reconstruction revealed that multiple pulmonary nodules remained in both lungs. (C) GGO lesions (arrow) found in the upper lobe of the right lung, measuring 7 mm × 6 mm. (D) First MWA was performed on after synchronous core‐needle biopsy, 16G‐ablation antenna was punctured to the center of the tumor lesion. (E) After two 4‐min ablation cycles with the power 60 W, we achieved a satisfactory ablation area, which is clearly seen and a large area of ground glass covers the entire tumor on the lung window of CT. (F–I) Computed tomography (CT) images of follow‐up. Follow‐up CT scans at 10 (F), 22 (G), 34 (H) and 59 months revealed significant shrinkage of the fibrous scars. (J) On September 18, 2019, Second microwave ablation was performed on two GGO lesions (arrow) adjacent to the upper lobe of the left lung, measuring 6 mm × 6 mm and 5 mm × 5 mm. (K–L) Two14G‐ablation antenna was punctured to the center of the tumor lesion, respectively. (M) The ablation was performed at a power of 50 W for 6 min and 50 W for 5 min. Postoperative CT scans revealed two larger GGOs with high density in the left lung. (N–Q) CT images of follow‐up. Follow‐up CT scans at 9 (N), 21 (O), 33 (P), and 58 (Q) months, further shrinkage of the fibrous scars was visible. (R–T) On May 21, 2020, Third microwave ablation was performed on GGO lesion (arrow) adjacent to the fibrous scars on upper lobe of the left lung. The 16G‐ablation antenna was placed (S) with an ablation power/time of 60 W/4 min, we achieved a satisfactory ablation area (T). (U–V) CT images of follow‐up. Follow‐up CT scans at 12 (U), 36 (V)months, the fibrous scars shows a fibrous hyperplasia. (W–X) The patient's pathological diagnosis of VATS‐biopsy was MIA‐AIS (H&E stain, 200×).

2.5. Follow‐Up and Outcome Assessment

Lesions at 4–6 weeks postablation were used as a baseline to determine their efficacy. According to the expert consensus for thermal ablation of lung tumors (edited in 2018), the local effect of the ablative response includes complete ablation, incomplete ablation, and local progression [21]. The initial ablation session followed follow‐up CT scans performed after 1, 3, 6, and 12 months via low‐dose thin‐slice CT (1 mm thickness). Contrast material‐enhanced CT of the chest was used to evaluate the potential for progression. If necessary, positron emission tomography‐computed tomography (PET‐CT) is feasible for assessing local response and distant metastasis. Tumors that were incompletely ablated or locally progressive and met the inclusion criteria were treated again with MWA.

The Functional Assessment of Cancer Therapy‐Lung (FACT‐L) (version 3) is a 44‐item self‐report instrument that measures multidimensional quality of life. We measured patient outcomes separately after the initial VATS and MWA procedures to evaluate the function and quality of life of patients with lung cancer undergoing treatment.

Improved criteria from the Response Evaluation Criteria in Solid Tumors guidelines were used to evaluate the local tumor progression of patients at 5 years of follow‐up [22, 23].

Local progression‐free survival (LPFS) was defined as the interval between the initial ablation and the first radiologic evidence of local progression. Event‐free survival (EFS) was defined as the time from the first treatment to the progression of any untreated residual nodule requiring ablation. Overall survival (OS) was defined as the time from the start of treatment to the last follow‐up or death. LPFS, EFS, and OS were assessed via the follow‐up results.

The variables were analyzed via the Statistical Package for the Social Sciences software (version 16.0). The means and standard deviations were determined for the measurement data and compared via the independent samples t‐test or Wilcoxon rank‐sum test. The χ ² test or Fisher's exact test was used to compare the categorical variables. The Kaplan–Meier method was used for the statistical analysis of survival. Statistical significance was set at p < 0.05.

3. Results

3.1. Patient Characteristics

A total of 47 patients with sMPLC characterized by mGGOs who underwent VATS combined with CT‐guided MWA were enrolled between April 2019 and December 2021. The patient characteristics of the study cohort are presented in Table 1. The median age of the patients was 60 years (range: 40–77 years), with 17 males and a high proportion of females (30/47, 62%). Six patients exhibited poor pulmonary function on preoperative examination; therefore, sublobectomy was selected for VATS. Among these patients, all high‐risk nodules resolved in 36 (76.6%) patients within a single hospitalization period, whereas high‐risk nodules resolved in 11 (23.4%) patients within two to four hospitalization periods. The median time interval between the first VATS and the last MWA operation was 5 days (range: 3–135 days).

TABLE 1.

The baseline information of patients.

Characteristics	Type	VATS‐MWA
		(N = 47) n (%)
Sex	Male	17 (36.2)
	Female	30 (63.8)
Age	Median (range)	60 (40–70)
	≥ 60	36 (76.6)
	< 60	11 (23.4)
Smoking history	Yes	8 (17.0)
	No	39 (83.0)
Medical comorbidities	Hypertension	21 (44.7)
	Diabetes mellitus	4 (8.5)
	Coronary artery disease	5 (10.6)
	Chronic obstructive lung disease	1 (2.1)
	Aplastic anemia a	1 (2.1)
	Previous malignancy	1 (2.1)
EV1/FVC b	≥ 0.7	40 (85.1)
	< 0.7	6 (12.7)
ECOG scores c	0–1	47 (100)
	2	0
Pathology of VATS d	AAH	0
	AIS	25 (53.2)
	MIA	13 (27.7)
	IA	9 (19.1)
Lymph node metastasis	Yes	0
	No	47 (100)
Pathology of biopsied GGOs e	AAH	22 (46.8)
	AIS	25 (53.2)
	MIA	0
	IA	0
Pathology of VATS‐biopsy	IA‐AAH	7 (14.9)
	IA‐AIS	2 (4.3)
	MIA‐AAH	2 (4.3)
	MIA‐AIS	11 (23.4)
	AIS‐AAH	13 (27.7)
	AIS‐AIS	12 (25.5)
Follow‐up f (months)	Median (range)	40 (30–64)
Hospitalization g	1	36 (76.6)
	2–4	11 (23.4)
Time interval (days) h	Median (range)	5 (3–135)

Note: Continuous data are presented as mean ± SD (range). Numbers in the parentheses represent percentages or range for categorical variables.

^a One patient had severe anaphylactoid purpura with only 20 × 10⁹ platelets.

^b One patients' results of the pulmonary function test were not obtained. (FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity)

^c Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score.

^d Postoperative pathological results were obtained from the resection of the primary lesion. AAH, atypical adenomatous hyperplasia; AIS, adenocarcinoma in situ; IA, invasive adenocarcinoma; MIA: minimally invasive adenocarcinoma.

^e Coaxial needle biopsy was performed at the time of ablation of the secondary lesion.

^f Follow‐up period of patients in these two groups was calculated from the date of MWA operation.

^g Number of hospitalizations in the course of multiple hybrid surgical treatments.

^h Time interval between the first VATS operation and the last MWA operation.

3.2. Nodule Characteristics

Details of the GGO characteristics are listed in Table 2. In patients with mGGOs, the number of nodules > 5 mm in diameter that had the potential to progress was counted. A total of 209 pulmonary nodules with clinical risk were identified in 47 patients, including 69 GGOs (33.0%) > 8 mm and 140 GGOs (67.0%) between 5 and 8 mm. The amount of solid components is indicative of aggressive behavior and invasive features. Therefore, we categorized the patients into three groups according to the type of nodule: Seven patients with pure GGOs (pGGOs) (14.89%), 37 patients with pGGOs and mGGOs (78.72%), and three patients with mGGOs (6.39%). The number of GGOs recorded for each patient is listed in Table 2. In this study, 17 patients (36.2%) presented 3 GGOs, 4 (10.0%) presented 4 GGOs, 12 (25.5%) presented 5 GGOs, and 8 (17.0%) presented more than 6 GGOs. The precise location of each GGO and the distribution pattern of mGGOs in each patient are indicated explicitly in Table 2. Among the patients, 44 (93.6%) had nodules distributed across the bilateral lung lobes, whereas only 3 (6.4%) had nodules in the ipsilateral lung lobe.

TABLE 2.

The characteristics of GGO.

Characteristics	Type	VATS‐MWA
		(N = 47) n (%)
Number of GGOs a	Total	209
	≥ 8 mm	69 (33.0)
	5–8 mm	140 (67.0)
GGO type pattern per patient b	pGGO	7 (14.9)
	pGGO + mGGO	37 (78.7)
	mGGO	3 (6.4)
Number of GGOs per patient	3	17 (36.2)
	4	10 (21.3)
	5	12 (25.5)
	6–9 c	8 (17.0)
Location of GGOs d	LUL	42 (20.1)
	LLL	28 (13.6)
	RUL	73 (34.8)
	RML	18 (8.7)
	RLL	48 (22.8)
	Unilateral lung nodules	3 (6.4)
	Bilateral lung nodules	44 (93.6)

Note: Continuous data are presented as mean ± SD (range). Numbers in the parentheses represent percentages or ranges for categorical variables.

^a In patients with multiple ground‐glass opacities (GGOs), we only counted the number of nodules larger than 5 mm in diameter that had the potential to progress.

^b We categorized the patients into three groups based on the amount of solid components of nodule.

^c Two patients had six GGOs, three patients had seven GGOs, two patients had eight GGOs, and one patient had nine GGOs.

^d LLL, left lower lobe; LUL, left upper lobe; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.

3.3. Perioperative Details of VATS‐MWA Surgery and Pathological Results

Table 3 presents the perioperative details of VATS‐MWA surgery, including information about the primary nodules identified during thoracoscopic surgery and the secondary nodules treated with microwave ablation. A total of 173 GGOs were removed, including 69 nodules (39.9%) measuring > 8 mm and 104 nodules (60.1%) measuring 5–8 mm. No tumor‐positive lymph nodes were observed. In 36 patients (76.6%), the primary lesions were in the dominant position. We removed the primary lesions at one time, and 11 patients (23.4%) had primary lesions in both the left and right thoracic cavities. Considering the greater degree of trauma associated with multiple‐nodule surgeries, we performed two‐stage surgeries on these patients. We removed the nonprimary nodule along with the primary nodule if it was adjacent to the primary lesion. Consequently, VATS was performed on 83 nodules. Of these, four and six nodules were removed from two patients. We recorded all the VATS procedures performed. Wedge resection was performed on 17 patients; lobectomy was performed on 7 patients; segmentectomy was performed on 10 patients; 2 patients underwent lobectomy combined with wedge resection; 7 patients underwent wedge resection combined with wedge resection; and 4 patients underwent segmentectomy combined with wedge resection. Postoperative pathological findings were retrospectively analyzed via VATS. The 47 primary lesions included 25 cases (53.2%) of adenocarcinoma in situ (AIS), 13 cases (27.7%) of minimally invasive adenocarcinoma (MIA), and 9 cases (19.1%) of invasive adenocarcinoma (IA).

TABLE 3.

Perioperative details of VATS‐MWA surgery.

Characteristics	Type	VATS‐MWA
		(N = 47)
Number of nodules treated	Total	173
	8 mm	69 (39.9)
	5–8 mm	104 (60.1)
Number of VATS procedures per patient	1	36 (76.6)
	2	11 (23.4)
GGOs resected by VATS per patient	Total	83
	1	27
	2	8
	3	10
	≥ 4	2
Type of lung surgery	Wedge resection + wedge resection	7 a
	Segmentectomy + wedge resection	4 b
	Lobectomy + wedge resection	2 c
	Lobectomy	7
	Segmentectomy	10
	Wedge resection	17
GGOs treated by ablation per patient	Total	90
	1	8
	2	14
	3	10
	4	6
Number of MWA procedures per patient d	Total	78
	Single	19
	2	25
	3	3
Model of ablation needle (G)	Total	90
	14	32 (35.5)
	16	58 (64.5)
Power of MWA Ablation per ggo (W)	Mean ± SD (range)	52.12 ± 9.07 (40–70)
Time per GGO (min)	Mean ± SD (range)	5.95 ± 2.12 (4–14)
Needle insertion depth	Mean ± SD (range)	11.81 ± 13.51 (4.22–74.62)
Number of remaining lesions	Total	36
	≥ 8 mm	0
	5–8 mm	36

Note: Continuous data are presented as mean ± SD (range). Numbers in the parentheses represent percentages or ranges for categorical variables.

^a Six of the seven patients underwent two wedge resections of bilateral pulmonary nodules, while one patient underwent combined wedge resections of the upper and lower lobes of the left lung (unilateral pulmonary nodules).

^b Four patients underwent segmental lung surgery on one side of the thoracic cavity, while wedge resection was performed on the opposite side.

^c Among them, one patient underwent lobectomy combined with wedge resection of the unilateral pulmonary nodules.

^d Some patients had two or more nodules ablated in a single microwave ablation.

Ninety secondary nodules, ranging from 1 to 4 among patients, were treated with CT‐guided MWA during single or multiple hospitalizations (1 to 4). To analyze the number of MWA procedures performed per patient, 19 patients underwent one MWA procedure, 25 patients underwent two MWA procedures, and 3 patients underwent three MWA procedures. We used 32 14G and 58 16G ablation needles, depending on the nodule size and the distance between the needle and the skin (needle insertion depth).

The mean needle insertion depth was 11.81 ± 13.51 cm (range: 4.22–74.62 cm). The mean ablation power for the nodules was 52.12 ± 9.07 W (range: 40–70 W). The mean ablation time per GGO was 5.95 ± 2.12 min (range: 4–14 min).

The pathological types of the nondominant lesions identified via MWA were confirmed via coaxial cutting needle biopsy. The confirmed types included 22 AAH (46.8%) and 25 AIS (53.2%) cases.

The pathological characteristics of both the primary and secondary lesions were thoroughly evaluated. The analysis included 7 cases (14.9%) of IA‐AAH, 2 cases (4.3%) of IA‐AIS, 2 cases (4.3%) of MIA‐AAH, 11 cases (24.3%) of MIA‐AIS, 13 cases (27.7%) of AIS‐AAH, and 12 cases (25.5%) of AIS‐AIS.

We achieved a 100% technical success rate for all 47 procedures. All lesions > 8 mm were identified in 47 patients, and 36 nodules measuring 5–8 mm in 15 patients were still being followed up.

3.4. Clinical Outcomes

As of April 30, 2024, no patient was lost to follow‐up. All patients were under clinical observation and did not receive further antitumor treatments, such as stereotactic radiation therapy, chemotherapy, targeted therapy, or immunotherapy.

The EFS is illustrated in Figure 3. At a median follow‐up of 41 months (range: 31–61 months), 6 patients (12.76%) had untreated residual nodules that increased in size or developed a solid component requiring ablation, whereas 41 patients (87.23%) demonstrated no change in size. The EFS was 100% at 3 years and 66.82% at 5 years.

FIGURE 3.

Event‐free survival of all patients.

During follow‐up, no local tumor progression or recurrence was observed in the 47 patients. Only one patient died from an unrelated cause (Figure 4).

FIGURE 4.

Local progression‐free survival of all patients.

The 3‐year OS rate for patients was 100%, and the 5‐year OS rate was 96.29%, with a median follow‐up of 40 months (range: 34–64 months) (Figure 5).

FIGURE 5.

Overall survival of all patients.

3.5. Side Effects and Complications

We evaluated all patients for short‐term postoperative side effects and complications during hospitalization and after discharge (Table 4). The common side effects of lung ablation include pain, cough, postablation syndrome, nonmassive hemoptysis, and pleural reactions. Among the 78 MWA procedures, 15 (31.9%) patients experienced pain. Persistent cough was observed in five (10.6%) patients. Postablation syndrome, which consists of low‐grade fever (< 38.5°C), nausea, vomiting, and general malaise, occurred in two (4.3%) patients, whereas one patient (2.1%) experienced nonmassive hemoptysis.

TABLE 4.

Side effects and complications of MWA procedures.

Side effects and complications	MWA (n = 47)	N (%)
Side effects
Pain	15	31.9
Persistent cough	5	10.6
Postablation syndrome	2	4.3
Nonmassive hemoptysis	1	2.1
Complications
Pleural effusion	3	6.4
Pneumothorax	7	14.9
Cavitation of the ablation zone	2	4.3
Hemorrhage	0
Abscess	0
Pneumonia	0
Bronchopleural fistula	0
Pulmonary oedema	0
Massive Hemoptysis	0

Note: Continuous data are presented as mean ± SD (range). Numbers in the parentheses represent percentages or range for categorical variables.

VATS combined with MWA generally has an excellent safety profile. The incidence of major complications ranged between 0% and 14.9%, usually occurring within the first month. Common complications include pneumothorax, pleural effusion, hemorrhage, and infection. Pleural effusion was observed in three patients (6.4%), pneumothorax occurred in seven patients (14.9%), and cavitation of the ablation zone was observed in two patients (4.3%). We did not encounter any other complications, such as hemorrhage, abscess, pneumonia, bronchopleural fistula, pulmonary edema, or massive hemoptysis.

3.6. The Quality of Life Measurement Scale for Patients is Listed in Table 5

TABLE 5.

Quality of life measurement scale FACT‐L for patients ^a .

Field	Treatment	After treatment	p
PWB b	10.51 ± 4.70	18.57 ± 2.41	< 0.001
SWB c	9.85 ± 3.18	14.70 ± 5.53	< 0.001
EWB d	12.29 ± 1.74	18.12 ± 2.38	< 0.001
FWB e	9.21 ± 3.53	16.91 ± 3.80	< 0.001
ACL f	19.40 ± 4.06	25.31 ± 3.06	< 0.001
Total	61.27 ± 10.50	93.63 ± 8.63	< 0.001

Note: Continuous data are presented as mean ± SD (range). Numbers in the parentheses represent percentages or range for categorical variables.

^a The FACT‐L (Functional Assessment of Cancer Therapy‐Lung, version 3) is a 44‐item self‐report instrument that measures multidimensional quality of life.

^b PWB, physical well‐being.

^c SWB, Social/family well‐being.

^d EWB, emotional well‐being.

^e FWB, functioning well‐being.

^f ACL, Additional concerns‐lung.

The findings of this study indicated improvements in the following areas of patient well‐being: physical, social, emotional, and functional, along with additional concerns specific to lung cancer patients. The quality of life of patients with lung cancer was significantly reduced after the first VATS procedure. However, subsequent MWA surgery did not affect the patient's quality of life, indicating an increasing trend compared with the first surgery. The difference between 61.27 ± 10.50 and 93.63 ± 8.63 was significant (p < 0.001).

4. Discussion

mGGOs exhibit diverse imaging characteristics and pathological types. Currently, the treatment approach for this condition is controversial. Diagnosing and managing such cases requires careful consideration of factors such as the pathological nature of the lesions, the sequence and timing of nodule interventions, the extent of surgical resection, and the patient's age and overall health status. This condition has no globally standardized diagnostic, treatment, or follow‐up protocol. Surgery remains the most efficient method for treating pulmonary nodules at high risk of malignancy and is based on noninvasive investigations or pathological diagnoses of lung cancer. According to the results of JCOG‐0802, the outcomes after segmentectomy are significantly better than those after lobectomy [24]. Consequently, some Chinese scholars recommend nonsurgical options such as image‐guided thermal ablation to treat mGGOs [25]. This study revealed that combining VATS for primary lesions and CT‐guided MWA for secondary lesions offers several advantages in treating mGGOs. This approach demonstrated a lower incidence of complications, minimal trauma, good tolerability, high repeatability, and fast recovery. Therefore, it can be considered a safe and successful treatment method without reported complications.

The presence of mGGOs in the lungs can originate from various sources, including MPLC and metastatic lung cancer [26, 27, 28, 29]. However, the prevailing consensus among numerous researchers is that mGGOs are more likely to be indicative of sMPLC than of metastatic lung cancer [7]. This distinction is clinically significant, as the underlying etiology of GGOs directly affects the appropriate treatment approach. VATS combined with CT‐guided MWA provides a clear, accurate, and comprehensive scheme for the pathological diagnosis of multiple pulmonary nodules. In our cohort, we used CT to locate the primary lesion before surgery, performed VATS for resection, and identified lesion pathology after the procedure. We selected CNB via a coaxial cannula before and after MWA to determine the pathology of the secondary lesions. The inability of MWA to provide tissues for histological analysis has traditionally been perceived as a disadvantage by thoracic surgeons. However, with advancements in ablation techniques, particularly the emergence of CNB via a coaxial cannula, we used a combination of pre‐ and post‐MWA biopsies to obtain pathological clarity for most secondary lesions in our study.

Biopsy performed in a separate session can potentially induce pneumothorax, hemorrhage, gas embolism, and cancer seeding along the biopsy puncture tract, increasing patient discomfort. However, the risk of potential complications was reduced when biopsies were performed immediately in conjunction with thermal ablation during the same procedure [30]. Several studies have demonstrated that even after complete ablation, pathological diagnosis and genetic testing can be performed on biopsy‐obtained samples [31, 32]. Wang et al. biopsied 74 GGOs before and after MWA to confirm their diagnostic efficacy [33]. A comprehensive pathological diagnosis is important for subsequent disease management. In this study, we combined the pathology of the primary lesion, determined through post‐VATS pathology, with the application of CNB, yielding a positive diagnosis rate of up to 100% for preinvasive lesions. Pathology data for both primary and secondary nodules were available for 47 patients. In this study, all secondary nodules were identified as high‐risk nodules by the MDT, whereas the remaining low‐risk nodules were not subjected to needle biopsy for pathological evaluation.

Removing all GGOs simultaneously in patients with sMPLCs is extremely difficult in clinical practice. Furthermore, some patients are unable to tolerate surgery because of underlying disease or advanced age. However, unresected main GGO lesions after primary surgery frequently have a risk of progression [11, 34]. Therefore, effective postoperative treatment is necessary to prevent disease recurrence or progression, particularly in patients who are unsuitable or unwilling to undergo additional surgery. Although there is currently no unified standard for the indications and methods of resection for mGGOs, there remains a consensus that surgical resection is the preferred treatment if there are no surgical contraindications and if the patient's cardiopulmonary function can tolerate the procedure, which aims to preserve as much normal lung tissue as possible and minimize the impact on the patient's lung function. Studies have demonstrated that sublobar resection has been widely accepted as an alternative option for patients who cannot undergo extensive surgical resection, as it can primarily preserve lung function [16]. In most cases, curative resection combined with limited resection or adequate follow‐up management based on thin‐section CT findings could provide acceptable oncologic outcomes in patients with mGGOs [35]. Some researchers have suggested that after removing the primary lesion, the prognosis may not be influenced by the continuous growth of residual GGOs, the presence of a new GGO lesion, or a lack of treatment [34, 36]. Numerous studies have proposed various surgical approaches for treating multiple nodules beyond two‐stage surgery [37, 38, 39]. These include one‐stage bilateral surgery for bilateral lung cancer, unilateral surgery combined with contralateral radiotherapy, and chemotherapy. However, these treatment approaches are also associated with different issues, such as increased patient harm, poor therapeutic outcomes, a high incidence of complications, and heightened patient anxiety, which can significantly affect quality of life.

VATS combined with MWA provides a novel solution for treating mGGOs. Owing to the frequent recurrence of nodules in patients, repeated VATS is impractical, even for minor sublobar resections. Conversely, patients can tolerate MWA, which is advantageous, helps minimize the loss of lung tissue, and allows for multiple treatments without significantly affecting lung volume or function. Furthermore, it can treat small, deep‐seated nodules that are difficult to access and remove via traditional wedge resection. As a result, it can maximize the preservation of lung tissue and minimize the risks associated with anesthesia in high‐risk patients. In our study, there were no serious perioperative complications or deaths, and all the patients were discharged smoothly. A total of 173 GGOs were removed. In 36 patients, the primary lesions were removed in a single procedure, whereas 11 required multiple surgeries because of the presence of primary lesions in the left and right thoracic cavities. Ninety secondary GGOs, varying in number from three to nine among patients, were treated with CT‐guided MWA during a single hospitalization or up to four hospitalizations. All the nodules were effectively treated with a combination of surgery and ablation. MWA has proven to be an effective treatment option for a second nodule, even if it is located near the major blood vessels in the hilum. We achieved a 100% technical success rate in 47 procedures and successfully identified all lesions > 8 mm in 47 patients. Hybrid surgery allowed thoracic surgeons to transition into a new era in which they held a scalpel in their right hand and a needle in their left hand.

To date, no clinical studies have investigated the outcomes and safety of VATS combined with CT‐guided MWA for GGO treatment. Reports exist only for VATS treatment of pulmonary nodules, and a limited number of cases involve thermal ablation or proton beam therapy for multiple pulmonary nodules. Nagata et al. [40] reported 48 patients with 53 tumors; the 3‐year OS rate after proton beam therapy was 91.7%, the 3‐year disease‐free survival rate was 85.4%, and the 3‐year local control rate was 92.5%. Forty‐two (89%) patients underwent anatomic resection. Stefano et al. [41] reported a 5‐year OS rate of 97.4% and a 3‐year disease‐free survival rate of 82%, which was significantly influenced by the stage of GGOs. Rirong Qu et al. [36] reported that 34 patients underwent simultaneous bilateral surgical resection of mGGOs, and the mean postoperative follow‐up for primary lung cancer patients was 28.4 (range: 3–39) months. No recurrences or deaths occurred at the final follow‐up. Park et al. [42] reported an excellent prognosis in a cohort of 58 patients with malignant pure GGOs who underwent surgical resection. There was no incidence of local recurrence or metastasis in any of these patients after 24 months of follow‐up. Kondo et al. [42] and Ichiki et al. [43] also reported a 100% 5‐year survival rate for patients with resected malignant GGO lesions. Yang et al. [19] enrolled 51 patients with 51 lung adenocarcinomas with GGOs treated with MWA. The 3‐year LPFS, cancer‐specific survival, and OS rates are 98%, 100%, and 96%, respectively [44]. To date, all patients who participated in this study have survived without procedure‐related deaths, local progression, tumor recurrence, mediastinal lymph node involvement, or distant metastasis. In our study, the median follow‐up time was 40 months (range: 30–64 months) after surgery. Among the 47 patients, only one died from another cause. LPFS, EFS, and OS rates were also significantly higher.

Furthermore, we demonstrated that hybrid surgery can be safely performed in patients with mGGOs. Like VATS and percutaneous ablation therapies, VATS combined with CT‐guided MWA is associated with common side effects and complications such as pain (15 cases, 31.9%), persistent cough (5 cases, 10.6%), postablation syndrome (2 cases, 4.3%), nonmassive hemoptysis (1 case, 2.1%), pleural effusion (3 cases, 6.4%), pneumothorax (7 cases, 14.9%), and cavitation of the ablation zone (2 cases, 4.3%) [45]. Other complications, such as hemorrhage, abscess, pneumonia, bronchopleural fistula, pulmonary edema, and massive hemoptysis, were rare and were not observed in our study. Pneumothorax is the most common complication associated with MWA. In this study, the incidence of pneumothorax was 14.9%, which was higher than that reported in previous studies (10%–67%) [46, 47]. The development of pneumothorax is closely related to factors such as the excessive number of ablation punctures, excessive length of the ablation needle puncture, proximity of the tumor to the pleura, and thin subcutaneous fat. In this study, most patients with pneumothorax required no treatment, which may be attributed to the increased amount of inflammatory exudate on the same side of the thoracic cavity after VATS, making pneumothorax more likely to occur after MWA. Intraoperative pneumothorax was effectively managed with needle aspiration and the placement of a closed chest tube. After closed chest drainage and high‐concentration oxygen therapy, follow‐up chest X‐rays 2 days later indicated resolution of the pneumothorax. The remaining patients exhibited no significant symptoms that improved after oxygen observation and management. The incidence of pleural effusion during ablation surgery is not high, primarily because of thermal injury. A small amount of pleural effusion can be observed after ablation, with wide variation in incidence rates (1%–60%). However, only 1%–7% of patients require clinical intervention [117]. In this study, no clinically significant pleural effusions were observed. The incidence of bleeding during pulmonary ablation ranges from 3% to 8% [117], with bleeding manifesting primarily as hemoptysis or hemothorax and rarely leading to hemorrhagic shock or acute respiratory failure. Bleeding often results from puncture injury to pulmonary vessels; accordingly, precise and rapid puncture is crucial for reducing bleeding complications. VATS was the preferred treatment for all nodules near the pulmonary hilar vessels, whereas MWA was predominantly used in the peripheral lung areas, resulting in minimal bleeding incidents. One patient experienced a puncture that ruptured a pulmonary vessel during the procedure, leading to pulmonary bleeding, which was observed as GGOs on CT and a high signal on magnetic resonance imaging. The bleeding site was promptly treated with MWA (30 W) for 30 s, leading to the cessation of hemoptysis. Postoperative treatment with thrombin injection from snake venom was effective in achieving hemostasis.

Recently, quality of life assessment has received increasing attention in oncology, as the medical paradigm has transitioned from a biomedical approach to one incorporating biological, psychological, and social aspects. Quality‐of‐life assessment has become an internationally recognized endpoint in clinical cancer treatment [48]. Quality of life is also an important reference indicator for assessing patients' overall condition, predicting prognosis, and evaluating therapeutic efficacy [49, 50]. With the changing humanistic perspective, cancer therapeutics increasingly focus on objective relief and patients' subjective experiences. Maintaining a positive emotional state enables patients to participate more actively in their treatment, making it easier to achieve favorable outcomes. Consequently, the FACT‐LCS (version 3) was used to evaluate patients' quality of life after treatment. Following the last MWA treatment, patients demonstrated significant improvements in scores related to activity, emotional well‐being, functional ability, and other factors (lung cancer‐specific concerns), with statistically significant differences compared with the initial VATS postoperative scores (p < 0.05).

Our study has several limitations. This was a retrospective study, and the number of cases was relatively small. Selection bias may have existed when patients with mGGOs were selected for hybrid procedures. This study was not designed to compare the outcomes of VATS combined with CT‐guided MWA with those of other treatments, such as VATS or CT‐guided MWA alone, stereotactic radiation therapy, chemotherapy, targeted therapy, and immunotherapy. As a consequence, a prospective, multicenter, randomized, controlled study is needed to clarify the safety and effectiveness of VATS combined with CT‐guided MWA for treating mGGOs. In the survey assessing the postsurgical quality of life of patients, assessments were conducted only at the first and last postoperative visits. This approach may have introduced bias into the results owing to the lack of interval assessments.

5. Conclusion

On the basis of the long‐term outcomes, VATS combined with CT‐guided MWA is a safe and effective treatment option for patients with mGGOs. The combination of VATS and CT‐guided MWA is a potential therapeutic application for preserving pulmonary function and treating mGGOs to the greatest extent possible. This hybrid surgical approach has broadened the treatment options available to thoracic surgeons and enhanced their procedural capabilities, marking an era in which surgeons can simultaneously use a needle and scalpel.

Author Contributions

B.H., C.Z., P.Y., Y.X., and D.L. designed the study; X.S., B.H., M.Z.B., C.Z., W.Y., C.S., Z.W., S.C., and D.F. performed the surgery; B.H., X.S., Z.M., and L.Z. drafted the manuscript; T.C. and T.S. analyzed the data; S.C., X.S., and D.L. revised the manuscript. All the authors approve of the final version to be published.

Disclosure

X.S. provided supervision and is the guarantor of this work, with full access to the data and responsibility for the integrity of the data and the accuracy of the data analysis.

Ethics Statement

This retrospective study was conducted in the Thoracic Surgery Department of ×× Hospital, China. This study was reviewed and approved by the Ethics Committee of ×× Hospital. All patients included in the study provided written consent to publish the related research results. Ethical approval for this study (Ethical Committee 2019‐×××) was provided by the Ethics Committee of ×× Hospital, Nanjing, China, on 28 February 2019.

Consent

The patients/participants provided written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Peer Review

This study was not commissioned and was externally peer reviewed.

Huang B., Zhan C., Yu P., et al., “Surgical Outcomes of Video‐Assisted Thoracic Surgery Combined With Computed Tomography‐Guided Microwave Ablation for Lung Cancer Presenting as Multiple Ground‐Glass Opacities: A 5‐Year Retrospective Cohort Study,” Thoracic Cancer 16, no. 14 (2025): e70120, 10.1111/1759-7714.70120.

Data Availability Statement

The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding author.