The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center
Original Article

The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center

Dongliang Bian1#, Yicheng Xiong1#, Kaiqi Jin1#, Yuming Zhu1, Huansha Yu2, Jie Dai1*, Gening Jiang1*

1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; 2Department of Animal Experimental Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

Contributions: (I) Conception and design: D Bian; (II) Administrative support: G Jiang, J Dai; (III) Provision of study materials or patients: Y Zhu; (IV) Collection and assembly of data: D Bian, Y Xiong; (V) Data analysis and interpretation: D Bian, K Jin; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work and should be considered as co-first authors.

*These authors contributed equally to this work and should be considered as co-corresponding authors.

Correspondence to: Gening Jiang, MD; Jie Dai, PhD. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Zhengmin Road 507, Yangpu District, Shanghai 200433, China. Email: geningjiang@tongji.edu.cn; tjdj1021@163.com.

Background: The effectiveness of segmentectomy for stage IA lung adenocarcinoma (IA-LUAD) has been well-documented. However, the efficacy and safety of wedge resection for peripheral IA-LUAD remains controversial. This study evaluated the feasibility of wedge resection in patients with peripheral IA-LUAD.

Methods: Patients with peripheral IA-LUAD who underwent wedge resection by video-assisted thoracoscopic surgery (VATS) at Shanghai Pulmonary Hospital were reviewed. Cox proportional hazards modeling was performed to identify predictors of recurrence. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoffs of identified predictors.

Results: A total of 186 patients (female/male, 115/71; mean age, 59.9 years) were included. Mean maximum dimension of consolidation component (MCD) was 5.6 mm, consolidation-to-tumor ratio (CTR) was 37%, and mean computed tomography value of tumor (CTVt) was −285.4 HU. With a median follow-up of 67 months (interquartile range, 52–72 months), the 5-year recurrence rate was 4.84%. Ten patients occurred recurrence postoperatively. No recurrence was observed adjacent to the surgical margin. Increasing MCD, CTR, and CTVt were associated with a higher risk of recurrence, with corresponding hazard ratios (HRs) of 1.212 [95% confidence interval (CI): 1.120–1.311], 1.054 (95% CI: 1.018–1.092), and 1.012 (95% CI: 1.004–1.019) with optimal cutoffs for predicting recurrence of 10 mm, 60%, and −220 HU, respectively. When a tumor had characteristics under these respective cutoffs, no recurrence was observed.

Conclusions: Wedge resection can be considered to be a safe and efficacious management strategy for patients with peripheral IA-LUAD, especially for MCD less than 10 mm, CTR less than 60% and CTVt less than −220 HU.

Keywords: Lung adenocarcinoma stage IA; wedge resection; recurrence


Submitted Jul 20, 2022. Accepted for publication Nov 25, 2022. Published online Jan 06 2023.

doi: 10.21037/jtd-22-1010


Highlight box

Key findings

• Wedge resection can be considered a safe and effective treatment for a subset of peripheral lung adenocarcinoma (LUAD) patients with stage IA.

What is known and what is new?

• Anatomical lobectomy or segmentectomy are standard treatment for stage IA non-small cell lung cancer (NSCLC). However, the efficacy of wedge resection for peripheral stage IA NSCLC remains controversial.

What is the implication, and what should change now?

• Wedge resection may provide similar efficacy versus anatomical lobectomy or segmentectomy for stage IA LUAD patients whose maximum dimension of consolidation component (MCD), the consolidation-to-tumor ratio of the maximum dimension of the tumor (CTR), and CT value of the tumor (CTVt) less than 10 mm, 60%, and −220 HU simultaneously.


Introduction

With the widespread use of high-resolution computed tomography (HRCT) scans and increased screening awareness, a growing number of lung cancer patients whose imaging manifestation were ground glass nodules (GGN), have been diagnosed at early stages (1,2). According to the results of the randomized phase III trial from the Lung Cancer Study Group, lobectomy plus systematic lymph node dissection has been the standard treatment for clinical T1N0M0 non-small cell lung cancer (NSCLC) for over 20 years (3). However, the results of more recent studies have demonstrated that lobectomy may not be the optimal surgical approach for all patients with early T1-stage NSCLC (4,5), suggesting that surgical alternatives to anatomical lobectomy may include a less invasive wedge resection (6-12). Wedge resection offers many potential benefits by preserving lung parenchyma and pulmonary function and lowering the risk of perioperative morbidity. It offers the possibility of curative therapy for patients who may not tolerate a lobectomy as well as those who present with postoperative recurrence or a secondary primary lung cancer (11,13). Although the data suggest that recurrence in patients with stage IA NSCLC who undergo wedge resection is higher than that of patients undergoing lobectomy, it is not significant (11,12). For these reasons, the indications for wedge resection in early-stage NSCLC has undergone exploration in recent years to improve the prognosis and quality of life of patients with early-stage NSCLC (14-16). However, the efficacy and safety of wedge resection for peripheral stage IA NSCLC remain controversial.

The purpose of this study was to assess the efficacy and safety of wedge resection among patients presenting with peripheral stage IA lung adenocarcinoma (IA-LUAD). A secondary aim was to identify predictors of recurrence after wedge resection for IA-LUAD and calculate cutoffs for these predictors. We present the following article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1010/rc).


Methods

Between January 2014 and December 2017, 196 consecutive patients who received wedge resection by video-assisted thoracoscopic surgery (VATS) in Shanghai Pulmonary Hospital were considered for inclusion in this retrospective study. Patients were diagnosed with pathological stage IA-LUAD by immunohistochemistry (IHC) in accordance to the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (8th edition) (17), and the World Health Organization (WHO) classification of tumors of the lung (4th edition) (18) postoperatively. At the first postoperative follow-up, no behavior of lung cancer was observed on computed tomography (CT) scan. The exclusion criteria were: (I) patient had an oncologic history; (II) the minimum distance between the tumor and resection margin was less than the maximum dimension of the tumor or 20 mm, whichever was less; (III) patient had received chemotherapy and/or radiotherapy postoperatively before recurrence; (IV) patient with LUAD nodules more than 1. Ten patients were excluded to yield a final study cohort of 186 patients. Patients underwent intentional wedge resection only when: (I) a multi-disciplinary team comprised thoracic surgeons, oncologists, pathologists, and radiologists, diagnosed the tumor as stage I LUAD, and (II) the tumor was located in the lung periphery and a wedge resection could achieve a sufficient surgical margin (≥ the maximum tumor dimension or 20 mm). In addition, patients who could not tolerate anatomical lobectomy or segmentectomy for comorbidities or other self-limited reasons underwent a compromised wedge resection. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by ethics committee of Shanghai Pulmonary Hospital (No. K20-433) and informed consent was taken from all the patients.

Clinical and pathological parameters of patients were sorted by gender, diagnostic age, tumor laterality, concomitant disease, postoperative complications, the IHC diagnosis upgraded from intraoperative frozen section (IFS), pathological subtypes of LUAD, and the status of any driver genomic mutations. Radiological parameters were reviewed from each patient’s presenting inspiratory HRCT and abstracted as the maximum dimension of the entire tumor (MTD) and that of its consolidation component (MCD), the mean computed tomography value of the tumor (CTVt) and that of its consolidation component (CTVc), and the consolidation-to-tumor ratio of the maximum dimension of the tumor (CTR). Lung windows were used to measure the MTD and CTVt, and mediastinal windows were used to measure the MCD and CTVc.

Statistical analysis

Categorical and continuous variables were compared between recurrence and non-recurrence patients by the chi-square test and unpaired t-test, respectively. Predictors for recurrence were analyzed by Cox proportional hazards modeling. The efficacy of MTD, MCD, CTVt, and CTR in predicting recurrence was calculated by receiver operating characteristic (ROC) curve analysis. Recurrence-free survival (RFS) was calculated from the time of surgery to disease relapse (LUAD relapse was confirmed by pathological and/or radiological analysis). All patients were followed to death, last contact, or an end date of December 31, 2021. A two-tailed P value <0.05 was considered statistically significant. All statistical analyses were performed by SPSS Statistics 26 (IBM Corp., Armonk, NY, USA).


Results

Characteristics of patients

Baseline characteristics are listed in Table 1. A total of 186 patients were included. The mean age was 59.9 years, and the number of female patients outnumbered male patients (115 vs. 71). On preoperative HRCT, the mean MTD was 14.4 mm (range, 5.9 to 29.5 mm), the mean MCD was 5.6 mm (range, 0 to 28.3 mm), the mean CTVt was −285.4 HU (range, −851.1 to 55.7 HU), and the mean CTR was 0.37. The numbers of patients with pure ground glass nodules (pGGN), part-solid ground glass nodules (mGGN), and solid nodules (SN) were 88, 73 and 25, respectively. After preoperative evaluation by the surgical team, 21 patients (11.3%) underwent wedge resection because they could not tolerate an anatomic resection, including 6, 10 and 5 patients with pGGN, mGGN, and SN, respectively. On pathological analysis, there were 24 patients (12.9%) whose subtypes included micropapillary (MPA) and/or solid (SPA) features; 18 (9.7%) patients were diagnosed as LUAD by IHC, which was upgraded from adenocarcinoma in situ (AIS) and microinvasive adenocarcinoma (MIA) by IFS.

Table 1

Baseline characteristics of patients with IA-LUAD undergoing wedge resection (n=186)

Variables Values
Age (years), mean (range) 59.9 (26, 82)
Tumor size (mm), mean (range)
   MTD 14.4 (5.9, 29.5)
   MCD 5.6 (0, 28.3)
CTVt (HU), range −285.4 (−851.1, 55.7)
Gender, n (%)
   Male 71 (38.2)
   Female 115 (61.8)
Number of nodules, n (%)
   Single 136 (73.1)
   Multiple 50 (26.9)
Feature of nodule, n (%)
   Pure GGN 88 (47.31)
   Mixed GGN 73 (39.25)
   Solid nodule 25 (13.44)
Laterality, n (%)
   Left 85 (45.7)
   Right 101 (54.3)
Pathological upgrading, n (%)
   Positive 18 (9.7)
   Negative 168 (90.3)
Pathological subtype, n (%)
   With MPA/SPA component 24 (12.9)
   Without MPA/SPA component 162 (87.1)
Drive gene mutation, n (%)
   Positive 82 (44.1)
   Negative 49 (26.3)
   Unknown 55 (29.6)
Selection of surgery, n (%)
   Intentional surgery 165 (88.7)
   Compromised surgery 21 (11.3)
Recurrence, n (%)
   Positive 10 (5.4)
   Negative 176 (94.6)
Recurrence rate (%), [n]
   1-year 0.54 [1]
   3-year 3.76 [7]
   5-year 4.84 [9]

LUAD, lung adenocarcinoma; MTD, maximum dimension of the entire tumor; MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; GGN, ground glass nodules; MPA/SPA, micropapillary or solid component.

All patients survived their operation and no major surgical-related complications were observed within 90 days postoperatively. Postoperative recurrence was observed in 10 patients. The numbers of patients with distant and local recurrence were 6 and 4, respectively. With a median follow-up of 67 months (interquartile range, 52–72 months), the 1-, 3-, and 5-year recurrence rates were 0.54%, 3.76%, and 4.84%, respectively. Among the 165 patients receiving planned wedge resections, 7 developed a recurrence, of which 6 recurred within 5 years (5-year recurrence rate: 3.64%). Among the other 21 patients who underwent a compromised wedge resection due to their inability to tolerate an anatomic resection, 3 developed recurrences within 5 years postoperatively (5-year recurrence rate: 14.29%).

Predictors of recurrence

The mean MTD (14.1 vs. 19.4 mm, P=0.002), CTVt (−300 vs. −28.4 HU, P=0.001), and CTR (34.1% vs. 89.8%, P<0.001) were significantly lower in non-recurrence patients as compared to in recurrence patients (Table 2). Additionally, there were significant differences in the proportion of the following imaging features as seen on HRCT between recurrence and non-recurrence patients: spicules margin (recurrence vs. non-recurrence: 90.0% vs. 55.7%, P=0.046), lobulated shape (recurrence vs. non-recurrence: 100.0% vs. 58.0%, P=0.007), and vascular passage (recurrence vs. non-recurrence: 20.0% vs. 67.6%, P=0.004). However, neither pathological subtypes (MPA or SPA) nor pathologic diagnosis of IHC upgraded from IFS was observed to be significantly associated with postoperative recurrence.

Table 2

The clinical characteristics of patients with IA-LUAD received wedge resection

Variables Non-recurrence (n=176) Recurrence (n=10) P value
Age (years), mean 59.5 66.4 0.052
Gender, n (%) 0.903
   Male 67 (38.1) 4 (40.0)
   Female 109 (61.9) 6 (60.0)
Nodule, n (%) 0.730
   Single 129 (73.3) 7 (70.0)
   Multiple 47 (26.7) 3 (30.0)
Tumor size (mm), mean
   MTD 14.1 19.4 0.002
   MCD 5.0 17.5 0.647
CTVt (HU) −300.0 −28.4 0.001
CTR (%) 34.1 89.8 <0.001
Laterality, n (%) 0.779
   Left 80 (45.5) 5 (50.0)
   Right 96 (54.5) 5 (50.0)
Pathologic upgrading, n (%) 0.602
   Positive 158 (89.8) 10 (100.0)
   Negative 18 (10.2) 0
Pathologic subtype, n (%) 0.620
   With MPA/SPA 22 (12.5) 2 (20.0)
   Without MPA/SPA 154 (87.5) 8 (80.0)
Drive gene mutation, n (%) 0.090
   Positive 75 (42.6) 7 (70.0)
   Negative/unknown 101 (57.4) 3 (30.0)
Pleural indentation, n (%) 0.620
   Positive 66 (37.5) 2 (20.0)
   Negative 110 (62.5) 8 (80.0)
Spicules of margin, n (%) 0.046
   Positive 98 (55.7) 9 (90.0)
   Negative 78 (44.3) 1 (10.0)
Lobulated shape, n (%) 0.007
   Positive 102 (58.0) 10 (100.0)
   Negative 74 (42.0) 0
Vacuole sign, n (%) 0.226
   Positive 36 (20.5) 4 (40.0)
   Negative 140 (79.5) 6 (60.0)
Vascular passage, n (%) 0.004
   Positive 119 (67.6) 2 (20.0)
   Negative 57 (33.4) 8 (80.0)

LUAD, lung adenocarcinoma; MTD, maximum dimension of the entire tumor; MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; CTR, the consolidation-to-tumor ratio of the maximum dimension of the tumor; MPA/SPA, micropapillary or solid component.

Table 3 depicts the results of the univariate analysis by Cox proportional hazards modeling. MTD [hazard ratio (HR) =1.194; 95% confidence interval (CI): 1.078–1.324; P=0.001], MCD (HR =1.212; 95% CI: 1.120–1.311; P<0.001), CTVt (HR =1.012; 95% CI: 1.004–1.019; P=0.004), CTR (HR =1.054; 95% CI: 1.018–1.092; P=0.003), and the imaging features concerning vascular passage on HRCT (HR =0.141; 95% CI: 0.030–0.666; P=0.013) were identified as predictors for recurrence.

Table 3

Cox proportional hazard model of recurrence for patients with IA-LUAD receiving wedge resection

Variables HR 95% CI P value
Age (years) 1.059 0.996–1.126 0.065
Gender
   Female 0.829 0.233–2.947 0.772
   Male
Number of primary nodule
   Single 1.289 0.331–5.017 0.715
   Multiple
MTD (mm) 1.194 1.078–1.324 0.001
MCD (mm) 1.212 1.120–1.311 <0.001
CTVt (HU) 1.012 1.004–1.019 0.004
CTR (%) 1.054 1.018–1.092 0.003
Laterality
   Right 0.827 0.239–2.859 0.764
   Left
Pathologic upgrading
   Positive 24.143 0.004–138,710.739 0.471
   Negative
Pathologic subtype
   Without MPA/SPA 0.549 0.116–2.589 0.448
   With MPA/SPA
Drive gene mutation
   Negative/unknown 0.322 0.083–1.247 0.101
   Positive
Pleural indentation
   Positive 2.487 0.527–11.728 0.250
   Negative
Spicules of margin
   Positive 7.533 0.954–59.467 0.055
   Negative
Lobulated shape
   Positive 46.210 0.238–8,960.132 0.154
   Negative
Vacuole sign
   Positive 2.428 0.684–8.622 0.170
   Negative
Vascular passage
   Positive 0.141 0.030–0.666 0.013
   Negative

LUAD, lung adenocarcinoma; HR, hazard ratio; CI, confidence interval; MTD, maximum dimension of the entire tumor; MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; CTR, the consolidation-to-tumor ratio of the maximum dimension of the tumor; MPA/SPA, micropapillary or solid component.

ROC curve analysis showed that the cutoffs for MCD, CTVt, and CTR were 10.5 mm, −217 HU, and 64%, and the area under the curve (AUC) for these three predictors was 0.908, 0.882, and 0.879 respectively. MCD was the most valuable predictor for recurrence (Figure 1). When the MCD was less than 10 mm, the postoperative recurrence rate of patients with IA-LUAD was 0.69% whereas it was 21.4% in patients whose MCD was greater than 10 mm. Furthermore, for patients with tumors that met all the cutoffs for MCD, CTR, and CTVt simultaneously, no recurrence was observed.

Figure 1 Area under the ROC curves used for predicting postoperative recurrence among patients with peripheral IA-LUAD. (A) MCD: AUC 0.908 (95% CI: 0.824–0.975), P<0.001. (B) CTVt: AUC 0.882 (95% CI: 0.798–0.966), P<0.001. (C) CTR: AUC 0.879 (95% CI: 0.817–0.941), P<0.001. MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; CTR, the consolidation-to-tumor ratio of the maximum dimension of the tumor; ROC, receiver operating characteristic; LUAD, lung adenocarcinoma; AUC, area under the curve.

Non-recurrence and recurrence patients after wedge resection

A total of 106 patients whose predictors of recurrence were within the identified safety thresholds were defined as a “selected group” of which none developed a postoperative recurrence (Figure 2).

Figure 2 Scatter plot indicating the selected criteria concerning (A) CTR and MCD and CTVt and (B) MCD for patients with peripheral IA-LUAD. The Y-axis in represents the MCD. The X-axis represents the CTR (A) and the CTVt (B). Selected was defined as the patients whose predictors of recurrence were within the identified safety thresholds. Danger was defined as the patients whose at least one predictor exceeded the thresholds. CTR, the consolidation-to-tumor ratio of the maximum dimension of the tumor; MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; LUAD, lung adenocarcinoma.

Due to the non-recurrence performance of pGGN in IA-LUAD, patients who had mGGN as their predominant imaging manifestation in selected group and patients occurred recurrence are listed in Table 4. Significant differences were observed between this selected group of patients who had no recurrence (n=21) compared to those who did (n=10). Compared with the mGGN patients in the selected group, the diagnostic age (66.4 vs. 60.2 years, P=0.049), MTD (19.5 vs. 14.7 mm, P=0.006), MCD (17.5 vs. 5.8 mm, P<0.001), CTR (90% vs. 41%, P<0.001), CTVt (−28.4 vs. −335.5 HU, P<0.001), and CTVc (17.3 vs. −138.7 HU, P<0.001) were significantly higher among the patients who developed recurrence. Details about these 10 patients who developed recurrence are presented in Table 5.

Table 4

Comparison between recurrence and selected group of patients who did not develop recurrence in the subset of mGGN patients

Variables Selected group (n=21) Recurrence (n=10) P value
Age (years), mean 60.2 66.4 0.049
Gender, n (%) 0.458
   Male 12 (57.1) 4 (40.0)
   Female 9 (42.9) 6 (60.0)
Nodule, n (%) 1.000
   Single 15 (71.4) 7 (70.0)
   Multiple 6 (28.6) 3 (30.0)
Tumor size (mm), mean
   MTD 14.7 19.5 0.006
   MCD 5.8 17.5 <0.001
CTR (%) 41 90 <0.001
CTV (HU)
   CTVt −335.5 −28.4 <0.001
   CTVc −138.7 17.3 <0.001
Laterality, n (%) 0.709
   Left 9 (42.9) 5 (50.0)
   Right 12 (57.1) 5 (50.0)
Pathologic upgrading, n (%) 0.533
   Positive 3 (14.3) 0
   Negative 18 (85.7) 10 (100.0)
Pathologic subtype, n (%) 0.237
   With MPA/SPA 1 (4.8) 2 (20.0)
   Without MPA/SPA 20 (95.2) 8 (80.0)
Drive gene mutation, n (%) 1.000
   Positive 13 (61.9) 7 (70.0)
   Negative/unknown 8 (38.1) 3 (30.0)
Resected size (mm)
   Maxima 80.7 81.0 0.983
   Minimal 23.2 21.5 0.641
Pleural indentation, n (%) 0.607
   Positive 12 (57.1) 8 (80.0)
   Negative 9 (42.9) 2 (20.0)
Spicules of margin, n (%) 0.106
   Positive 12 (57.1) 9 (90.0)
   Negative 9 (42.9) 1 (10.0)
Lobulated shape, n (%) 0.012
   Positive 11 (52.4) 10 (100.0)
   Negative 10 (47.6) 0
Vacuole sign, n (%) 0.417
   Positive 5 (23.8) 4 (40.0)
   Negative 16 (76.2) 6 (60.0)
Vascular passage, n (%) 0.003
   Positive 16 (76.2) 2 (20.0)
   Negative 5 (23.8) 8 (80.0)

mGGN, part-solid ground glass nodules; MTD, maximum dimension of the entire tumor; MCD, maximum consolidation component of the tumor; CTR, the consolidation-to-tumor ratio of the maximum dimension of the tumor; CTVt, mean computed tomography value of the tumor; CTVc, the mean computed tomography value of the consolidation component of the tumor; MPA/SPA, micropapillary or solid component.

Table 5

Details of patients after wedge resection who developed recurrence

No. Gender Age (years) Location MTD (mm) MCD (mm) CTVt (HU) CTVc (HU) Pathology subtype Gene mutation Status [RFS, months] Recurrent site
1 F 72 LUL 27.6 17.7 −217.1 18.1 APA L858R Alive [40] Pleural
2 M 69 LUL 10.7 7.5 −156.4 −44.8 PPA + MPA Unknown Dead [28] Liver
3 M 71 RLL 13.5 10.7 −62.8 5.9 LPA Wild type Censored [21] Brain, bone
4 M 63 RLL 12.2 12.2 −27.7 −27.7 SPA + MPA Wild type Dead [19] Brain
5 F 75 LUL 14.9 13.9 −1.5 40.4 APA L858R Alive [27] Lung
6 F 62 RLL 14.8 14.8 9.8 9.8 PPA + SPA 19-Del Alive [68] Bone
7 F 66 LLL 21.8 21.8 54.2 54.2 APA 19-Del Alive [51] Lung
8 F 59 LLL 22.1 22.1 54.6 54.6 SPA ROS1 Alive [14] Bone
9 F 64 RUL 28.6 26.2 34.0 34.0 APA L858R Alive [11] Brain, bone
10 M 63 RUL 28.3 28.3 28.5 28.5 APA L858R Alive [31] Lung

MTD, maximum dimension of the entire tumor; MCD, maximum consolidation component of the tumor; CTVt, mean computed tomography value of the tumor; CTVc, the mean computed tomography value of the consolidation component of the tumor; RFS, recurrence-free survival; F, female; LUL, left upper lobe; APA, acinar predominant LUAD; LUAD, lung adenocarcinoma; M, male; PPA, papillary predominant LUAD; MPA, micropapillary predominant LUAD; RLL, right lower lobe; LPA, lepidic predominant LUAD; SPA, solid predominant LUAD; LLL, left lower lobe; RUL, right upper lobe.


Discussion

In recent years, there has been ongoing debate regarding the optimal surgical approach for patients presenting with IA-LUAD. A few studies have demonstrated equivalent outcomes between lobectomy and sub-lobar resection in this population (6,11). There are several benefits of a wedge resection over an anatomic resection. The former is more likely to preserve postoperative pulmonary function and lung parenchyma (11), reduce the duration of the operation and intraoperative complications, and may be better suited for elderly patients or those with significant comorbidities or other contraindications to an anatomic lobectomy (7). In this retrospective study, we assessed the safety and efficacy of wedge resection for patients with peripheral IA-LUAD and explored the indications for a wedge resection in this population, which may help guide the selection of an optimal surgical strategy.

To our knowledge, previously published prospective randomized clinical trials (RCT) and retrospective studies have mainly focused on the feasibility of sub-lobar resections for patients with IA-LUAD. Prior studies have shown that MTD plays an important role in determining the pathological features of NSCLC (2). Clinical trial JCOG0201 defined non-invasive NSCLC to be a tumor with radiological criteria of CTR 0.25 or less in stage cT1a-b patients (≤20 mm size) (14), and demonstrated the feasibility of a limited surgical resection such as segmentectomy and wedge resection for IA-LUAD with a CTR 0.5 or less in cT1 patients (≤30 mm size) (9,14,19-21). A phase II prospective clinical trial (JCOG0804) is currently evaluating the safety and efficacy of wedge resection for early-stage peripheral NSCLC with a CTR of 0.25 or less (7). Finally, CALGB-140503 has been launched to compare wedge resection and lobectomy for peripheral early-stage NSCLC (22). However, these studies did not assess the predictive factors for recurrence in IA-LUAD patients clearly, nor did they contribute a predictive model to guide the surgical procedure.

The results of our study demonstrated that the most valuable predictive factors for recurrence were MCD, CTR, and CTVt, and no recurrence was observed among peripheral IA-LUAD patients with pGGN after wedge resection. Our ROC curve analysis confirmed that when the imaging features of a peripheral IA-LUAD tumor met the requirements of MCD less than 10 mm, CTR less than 0.6, and CTVt less than −220 HU simultaneously, a wedge resection was not only feasible, but no recurrence was also observed postoperatively. With these radiographic criteria met, no recurrence patient was observed after wedge resection, suggesting that these radiographic criteria were appropriate indicators for a limited resection in patients with IA-LUAD. In addition, for patients with tumor CTR greater than 0.6, recurrence rate after sub-lobar resection was improved over lobectomy, and the former may increase the risk of recurrence in this subset of patients.

Consistent with previous research results, the most important factor for the successful treatment of IA-LUAD is the surgical margin (7,12,23). Based on the experience at our center, in patients with peripheral IA-LUAD, a wedge resection, compared to a segmentectomy or lobectomy, could ensure sufficient distance between nodules and resected margins equally. Moreover, wedge resection is a time-tested and safe surgical technique with many benefits over an anatomical resection such as decreasing the duration of chest tube placement and the inpatient length of stay.

Furthermore, one of the disadvantages of a sub-lobar resection is inadequate lymph node dissection, especially for cT1-LUAD with a solid component. Wedge resection without lymph node sampling is considered to be inadequate even for small and peripheral nodules due to the possibility for locoregional recurrence (6,24-26). Therefore, lymph node sampling plays a crucial role in wedge resection to stage cT1-stage LUAD pathologically and guide adjuvant treatment and follow-up strategies. In this retrospective analysis, all patients received wedge resection combined with regional lymph node sampling or dissection, and the results of their IHC postoperatively confirmed that none of them had lymph node involvement.

It is worth point out that, from a previous study, pathological subtypes (27) and the status of drive-gene mutations (28) may influence the recurrence of early-stage LUAD postoperatively. However, a significant difference in the distribution of these 2 factors between recurrence and non-recurrence patients was not observed in our study, which demonstrated that the status of drive gene mutations and the component of MPA/SPA did not affect recurrence in wedge-treated patients with IA-LUAD postoperatively. This seemingly contradictory phenomenon may be attributed to the fact that there was a relatively small number of patients developed recurrence in our study.

Limitations

There are several limitations to our findings. First, this research is a retrospective analysis based on a single center, which is inherently prone to selection bias. Second, the sample size of this study is small. Third, while a limited resection for early-LUAD has similar 5-year survival as an anatomical resection, it may decrease long-term survival (6). Due to our limited follow-up, this study does not explore outcomes beyond ten years. As mentioned, a larger sample size and a longer follow-up period is warranted and will be the focus of future study. Fourth, this study included 21 patients who should undergo lobectomy according to guideline, but only compromising wedge resection was performed for various reasons, including cardiovascular diseases, limitation of pulmonary function, and others comorbidities. Fifth, the detail information of lymph nodes dissection or sampling was not included. However, patients without lymph nodes sampling were excluded in this study to ensure accurate staging and prognostic information.


Conclusions

Among patients with peripheral IA-LUAD, wedge resection provides a similar recurrence rate and decreased morbidity compared to an anatomic resection. MCD, CTR, and CTVt are predictors for recurrence. The cutoffs for these 3 predictors are 10 mm, 60%, and −220 HU. When these cutoffs were met simultaneously, patients developed no postoperative recurrence over the course of follow-up. A wedge resection for IA-LUAD patients can be performed safely and efficaciously, but larger scale and long-term follow-up are necessary for further study.


Acknowledgments

Funding: This study was supported by the National Key R&D Program of China (No. 2019YFC1315803), and the National Natural Science Foundation of China (No. 82070022).


Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1010/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1010/dss

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1010/coif). The authors have no conflicts of interest to declare.

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 (as revised in 2013). The study was approved by ethics committee of Shanghai Pulmonary Hospital (No. K20-433), and informed consent was taken from all the patients.

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Cite this article as: Bian D, Xiong Y, Jin K, Zhu Y, Yu H, Dai J, Jiang G. The efficacy and safety of wedge resection for peripheral stage IA lung adenocarcinoma: a real-world study based on a single center. J Thorac Dis 2023;15(1):54-64. doi: 10.21037/jtd-22-1010

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