Abstract
Background
Ongoing studies are currently investigating the extent of surgical resection required for subsolid cancers. This study aimed to investigate the predictive factors related to recurrence in patients with clinical stage IA subsolid cancer who underwent either lobectomy or sublobar resection.
Methods
This was a prospective multicenter observational study conducted in eight qualifying university teaching hospitals between April 2014 and December 2016. A total of 173 patients with subsolid nodules pathologically confirmed to have primary lung adenocarcinoma and stage IA disease were included in the final analysis. All patients underwent lobectomy, segmentectomy, or wedge resection performed by experienced thoracoscopic surgeons at each site. The surgical procedure was chosen based on the decision of the surgeons involved. The primary endpoint was time to recurrence (TTR).
Results
The study population was 43.9% (76 of 173) male with a mean age of 60.7 years. During the median follow‐up period of 5.01 years, nine patients (5%) experienced disease recurrence. In the multivariable analysis, tumor size (size ≥2 cm) (hazard ratio: 73.717, 95% confidence interval [CI]: 3.635–895.036; p < 0.001) and stage IA3 (hazard ratio: 62.010, 95% CI: 2.837–855.185; p < 0.001) were independent predictors of tumor recurrence. When analyzing the recurrence outcome in patients according to surgical procedure, no significant difference was found in TTR among the three groups (i.e., lobectomy, segmentectomy, and wedge resection; p = 0.99).
Conclusions
Patients with radiologically subsolid lung adenocarcinoma measuring <3 cm could be candidates for sublobar resection instead of lobectomy.
Keywords: lobectomy, lung adenocarcinoma, segmentectomy, subsolid nodule, wedge resection
Highlights
This study aimed to investigate risk factors related to recurrence in patients with clinical stage IA subsolid cancer who underwent either lobectomy or sublobar resection.
The main results showed excellent surgical outcomes regardless of surgical procedure, subsolid nodule subtype and solid component size.
Our results validate subjects eligible for sublobar resection recommended by the NCCN 2020 guideline and provide surgeons with a rationale for choosing a less extensive surgical alternative for clinical stage IA adenocarcinomas observed as subsolid nodules without compromising patient outcomes.
INTRODUCTION
Computed tomography (CT) is being increasingly used for lung cancer screening, and findings of incidentally detected subsolid nodules (either pure ground‐glass nodule [GGN] or part‐solid nodule [PSN]) are increasing. 1 , 2 , 3 Patients with stage IA adenocarcinoma observed as subsolid nodules have been reported to have a better prognosis as compared with those that are pure solid adenocarcinoma. 4 , 5
Lobectomy demonstrates a great advantage over sublobar resection and has been naturally recommended as the standard surgical procedure for early‐stage non‐small cell lung cancer (NSCLC). 6 However, there is renewed interest in conducting sublobar resection in selected cases with early‐stage NSCLC. Several studies have shown that sublobar resection achieves equivalent surgical outcomes to those of lobectomy in clinical stage IA subsolid lung cancer. 7 , 8 , 9 Previous guidelines from the Fleischner Society recommend the management of persistent subsolid nodules; however, the optimal extent of surgical resection and mediastinal lymph node dissection has yet to be determined. 10 , 11 This study aimed to investigate predictive factors related to the recurrence in patients with clinical stage IA subsolid cancer who underwent either lobectomy or sublobar resection.
METHODS
Patient selection
This study was a prospective multicenter observational study conducted in eight qualifying university teaching hospitals. Between April 2014 and December 2016, 250 patients with subsolid nodules indicated for surgical resection under video‐assisted thoracoscopic surgery (VATS) were screened and enrolled from the eight sites according to the inclusion criteria. Of the 250 patients from the LOGIS trial, 12 we prospectively enrolled all eligible patients according to the inclusion criteria of the present study as follows: (i) aged more than 20 years, (ii) pulmonary lesion with a GGN component of greater than 50%, (ii) a lesion size of less than 3 cm, (iv) clinical stage IA disease (according to the TNM classification scheme, eighth edition), and (v) pathologically confirmed as having primary lung adenocarcinoma or adenocarcinoma in situ (AIS). The exclusion criteria were as follows: (i) an unwillingness or inability to provide consent, (ii) disease pathologically confirmed as benign or something other than primary lung adenocarcinoma, (iii) patients with synchronous subsolid or pure solid tumors, (iv) patients who were classified as not having stage IA disease, and (v) follow‐up loss. The study protocol was approved by the institutional review boards or ethics committees at each participating center and all participants provided their written informed consent.
Finally, 173 patients with subsolid nodules pathologically confirmed to have primary lung adenocarcinoma and pathological stage IA disease (according to the TNM classification scheme, eighth edition), were included for final analysis (Figure 1). All patients underwent thoracoscopic surgery conducted by experienced thoracoscopic surgeons at each site. All data entry, data management, and analyses were coordinated or performed at a data‐coordinating center. In our database, the following clinical and pathological characteristics were recorded: age, sex, clinical history including hypertension, diabetes mellitus, hepatitis, cancer (other than lung cancer), surgery (other than lung cancer surgery), heart disease, and smoking, maximum tumor size including GGN component, solid size, stage based on the eighth edition of the TNM classification scheme, surgical method, and pathological type including histological subtype.
FIGURE 1.
Flow chart of patient selection
Chest CT examinations
All preoperative chest CT examinations were performed using a (at minimum) 16‐slice multi‐detector single‐ or dual‐source CT scanner. A chest CT was performed in all eligible participants in a craniocaudal direction during inspiration without contrast material enhancement by using the following scan parameters: tube voltage, 120 kV; tube current, 100 mAs, section thickness and interval, 1.0 and 1.0 mm, respectively.
Image and pathology analysis
All image analyses were performed at the data‐coordinating center by an experienced board‐certificated thoracic radiologist with 10 years of experience in chest CT imaging who was blinded to the clinical and histological findings. TNM staging was based on the eighth edition of the TNM classification proposed by the International Association of Study of Lung Cancer (IASLC). 13
Subsolid nodules were distinguished depending on the presence of GGN and solid components. Pure GGN was defined as a nodule without a solid component and a PSN was defined as a lung lesion with both a GGN and a solid component. 11 The maximum diameter on the single largest dimension (axial, sagittal, or coronal images) was measured on a lung window and recorded for determining the size of the solid component and whole target nodule. For quantitative volume analysis, commercialized software (AVIEW Research) was used to measure the whole tumor volume. The lesion segmentation was performed on a lung window setting (width, 1500 HU; level, −600 HU) images. The whole volume of interest (VOI) of the target lesion was isolated by semi‐automatic segmentation. If the segmented border of the target lesion was incorrect, the reviewer manually corrected the VOI according to the border of the target lesion on slices including the target lesion on axial images. When the observer approved the definition of the margin, the program automatically calculated the tumor volume.
The postoperative pathological diagnosis was made according to the IASLC/American Thoracic Society/European Respiratory Society classification as adenocarcinoma in situ, minimally invasive adenocarcinoma, or invasive adenocarcinoma which was further divided into lepidic predominant, acinar predominant, papillary predominant, micropapillary predominant, solid predominant, and invasive mucinous adenocarcinoma. The predominant pattern was defined as the pattern with the largest percentage (not necessarily 50% or higher). 14
Follow‐up protocol
All patients were followed up from the day of surgery. They were examined physically and underwent chest CT covering cervical to abdominal lesions every 3–6 months for the first two years. Thereafter, they were examined physically and by chest CT every six months during the third year and then once per year for subsequent years up to five years. The primary endpoint of the present study was time to recurrence (TTR), which was defined as the time from the day of surgery to the day of first recurrence. Local recurrence was defined as disease recurrence at the surgical resection margin, ipsilateral hilum, and/or mediastinum. All other sites of failure were considered distant recurrences. Patients who died from other causes during the study period were considered to be censored with no event when calculating TTR. Observations were censored at the last follow‐up at which the patient was alive or lost to follow‐up.
Statistical analysis
The differences between categorical variables were analyzed by chi‐squared test. Differences between continuous variables were analyzed by the one way ANOVA test or Kruskal‐Wallis test. A Cox proportional‐hazards regression model was used to evaluate the risk factors for lung cancer‐related recurrence among the different surgical methods. Statistically significant findings on univariate analysis were subsequently included in the multivariate analysis. Only variables with p‐values of less than 0.20 during univariate analysis were added to the final multivariate models to prevent model overfitting. From the Cox proportional‐hazards model, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with using Firth correction. Concordance (C) statistics were used to compare the predictive prognosis among the models. 15 Survival curves were estimated by the Kaplan–Meier method according to the three different surgical groups. Their comparisons were performed by using the log‐rank test. Here, p‐values of less than 0.05 were considered statistically significant. All statistical analyses were performed using commercial software (R version 3.3.2 from the R Foundation for Statistical Computing and MedCalc version 12 from MedCalc).
RESULTS
Patient characteristics
Overall, the study population consisted of 173 patients with clinicopathological stage IA primary lung adenocarcinoma; among these, 43.9% (76 of 173) were male with a mean age of 60.7 years. The clinical characteristics of the patient population according to surgical procedures are listed in Table 1. In the lobectomy group, history of cancer was significantly lower compared to segmentectomy and wedge resection groups (p = 0.039). The tumor size, solid component and volume were higher in the lobectomy group than segmentectomy and wedge resection groups (all p < 0.001). The lobectomy group had higher part‐solid nodules than segmentectomy and wedge resection groups (p < 0.001), whereas the wedge resection group had higher pure GGN than segmentectomy and lobectomy groups (p < 0.001).
TABLE 1.
Baseline characteristics of 173 patients with pathological stage IA primary lung adenocarcinoma
| Variables | Lobectomy (n = 63) | Segmentectomy (n = 41) | Wedge resection (n = 69) | p‐value |
|---|---|---|---|---|
| Sex (male %) | 23 (36.5) | 19 (46.3) | 34 (49.2) | 0.191 |
| Age (years) | 59.84 ± 8.72 | 61.12 ± 10.68 | 61.37 ± 11.49 | 0.534 |
| Hypertension, n (%) | 21 (33.3) | 17 (41.5) | 20 (28.9) | 0.627 |
| Diabetes, n (%) | 10 (15.8) | 9 (21.9) | 9 (13.0) | 0.590 |
| Hepatitis, n (%) | 3 (4.7) | 3 (7.3) | 5 (7.2) | 0.597 |
| Cancer a , n (%) | 12 (19.0) | 15 (36.6) | 26 (37.6) | 0.039 |
| Surgery b , n (%) | 29 (46.1) | 28 (68.3) | 42 (60.8) | 0.139 |
| Heart disease, n (%) | 4 (6.3) | 9 (21.9) | 5 (7.2) | 0.962 |
| Smoking status | 0.222 | |||
| Current/former, n (%) | 16 (25.4) | 16 (39.0) | 32 (46.4) | |
| Never, n (%) | 47 (74.6) | 25 (61.0) | 37 (53.6) | |
| Tumor size, mm | 16.88 ± 5.07 | 15.64 ± 3.47 | 14.44 ± 5.15 | 0.019 |
| Solid component, mm | 7.24 ± 4.94 | 4.60 ± 3.24 | 4.19 ± 3.87 | <0.001 |
| Whole tumor volume, mm3 | 2408.66 ± 2319.01 | 1805.94 ± 1372.85 | 1687.53 ± 2018.48 | 0.025 |
| Pure GGN | 9 (14.3) | 11 (26.8) | 23 (33.3) | 0.029 |
| Part solid nodule | 54 (85.7) | 30 (73.2) | 46 (66.7) | 0.025 |
| Location, n (%) | 0.007 | |||
| Right upper lobe | 21 (33.3) | 8 (19.5) | 23 (33.3) | |
| Right middle lobe | 9 (14.3) | 0 | 5 (7.2) | |
| Right lower lobe | 9 (14.3) | 6 (14.6) | 19 (27.5) | |
| Left upper lobe | 17 (26.9) | 21 (51.3) | 15 (21.9) | |
| Left lower lobe | 7 (11.2) | 6 (14.6) | 7 (10.1) | |
| p‐stage | 0.066 | |||
| Stage IA1 | 12 (19.0) | 7 (17.1) | 23 (33.3) | |
| Stage IA2 | 40 (63.5) | 32 (78.0) | 41 (59.5) | |
| Stage IA3 | 11 (17.5) | 2 (4.9) | 5 (7.2) | |
| Histology type | 0.259 | |||
| MIA | 12(19.0) | 10(24.4) | 21 (30.4) | |
| Invasive adenocarcinoma | 51(81.0) | 31(75.6) | 48 (69.6) |
Note: Values are presented as mean ± standard deviation or patient number with (%).
Abbreviations: GGN, ground‐glass opacity; MIA, minimally invasive adenocarcinoma.
History of cancer included all cancers other than lung cancer.
History of surgery included surgery other than lung cancer surgery.
Recurrence outcome
During the median follow‐up period of 5.01 years (interquartile range: 4.33–5.45 year), nine patients experienced disease recurrence: ipsilateral or contralateral lung (n = 6), brain (n = 2), and LN (mediastinum) (n = 1). Disease recurrence was confirmed by means of biopsy or surgery in four (44%) patients, while the remaining five (56%) patients were confirmed by means of CT, MRI or PET scan.
When patients were divided into lobectomy, segmentectomy, and wedge resection subgroups, three patients with disease recurrence underwent wedge resection, two underwent segmentectomy, and four underwent lobectomy. The pathological TNM stage of the nine patients with disease recurrence was stage IA3. All patients were confirmed to have invasive adenocarcinoma (five with papillary predominant and four with acinar predominant).
In a univariate Cox regression analysis, tumor size (size ≥ 2 cm) (HR: 63.404, 95% CI: 3.161–971.714; p < 0.001), tumor volume (volume ≥ 10[*100] mm3) (HR: 11.012, 95% CI: 0.559–220.872; p = 0.017) and stage IA3 (HR: 47.787, 95% CI: 2.211–832.707; p < 0.001) were deemed predictors of disease recurrence (Table 2). To determine the prognostic predictors between surgical procedures, we constructed several models with additional parameters. All variables met a proportional‐hazards assumption. In models 2 and 5, tumor size (size ≥ 2 cm) (HR: 73.717, 95% CI: 3.635–895.036; p < 0.001) and stage of IA3 (HR: 62.01, 95% CI: 2.837–855.185; p < 0.001) were independent predictors of tumor recurrence (Table 3).
TABLE 2.
Univariate analysis using a Cox proportional‐hazards regression model
| Time‐to recurrence | ||||
|---|---|---|---|---|
| Characteristic | HR | 95% CI | p value | |
| Age | 1.056 | 0.982 | 1.135 | 0.143 |
| Sex (male) | 0.623 | 0.157 | 2.475 | 0.503 |
| Hypertension | 1.689 | 0.351 | 8.134 | 0.513 |
| Diabetes | 1.406 | 0.176 | 11.249 | 0.748 |
| Hepatitis | 1.093 | 0.049 | 24.501 | 0.952 |
| Cancer | 1.643 | 0.341 | 7.912 | 0.536 |
| Surgery | 5.897 | 0.739 | 47.230 | 0.095 |
| Heart disease | 0.890 | 0.022 | 8.871 | 0.523 |
| Smoking a | 1.501 | 0.402 | 5.601 | 0.546 |
| Tumor size, cm | ||||
| Size < 2 cm | 1 (ref) | |||
| Size ≥ 2 cm | 63.404 | 3.161 | 971.714 | <0.001 |
| Subsolid nodule subtype | ||||
| Pure GGN | 1 (ref) | |||
| Part‐solid nodule | 2.093 | 0.259 | 16.938 | 0.489 |
| Solid size, mm | ||||
| Size < 6 mm | 1 (ref) | |||
| Size ≥ 6 mm | 2.245 | 0.559 | 9.012 | 0.254 |
| Tumor volume (*100), mm3 | ||||
| Volume < 10 | 1 (ref) | |||
| Volume ≥ 10 | 11.012 | 0.559 | 220.872 | 0.017 |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 0.839 | 0.153 | 4.613 | 0.840 |
| Wedge resection | 0.864 | 0.190 | 3.935 | 0.851 |
| Stage | ||||
| Stage IA1 | 1 (ref) | |||
| Stage IA2 | 0.867 | 0.005 | 25.373 | 0.623 |
| Stage IA3 | 47.787 | 2.211 | 832.707 | <0.001 |
| Histology type | ||||
| MIA | 1 (ref) | |||
| Invasive adenocarcinoma | 2.723 | 0.341 | 21.776 | 0.345 |
Abbreviations: AIS, adenocarcinoma in situ; CI, confidence interval; GGN, ground‐glass opacity; HR, hazard ratio; MIA, minimally invasive adenocarcinoma.
smoking included all former and current smokers.
TABLE 3.
Multivariate analysis using a Cox proportional‐hazards regression model
| Time‐to recurrence | ||||
|---|---|---|---|---|
| Model 1 | HR | 95% CI | p value | |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 0.839 | 0.153 | 4.613 | 0.840 |
| Wedge resection | 0.864 | 0.190 | 3.935 | 0.851 |
| Time‐to recurrence | ||||
| Model 2 | HR | 95% CI | p‐value | |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 2.368 | 0.443 | 12.664 | 0.304 |
| Wedge resection | 1.241 | 0.27 | 5.704 | 0.765 |
| Tumor size, cm | ||||
| Size < 2 cm | 1 (ref) | |||
| Size ≥ 2 cm | 73.717 | 3.635 | 895.036 | <0.001 |
| Time‐to recurrence | ||||
| Model 3 | HR | 95% CI | p‐value | |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 0.935 | 0.174 | 5.017 | 0.932 |
| Wedge resection | 1.176 | 0.258 | 5.373 | 0.822 |
| Tumor volume (*100), mm3 | ||||
| Volume < 10 | 1 (ref) | |||
| Volume ≥ 10 | 11.447 | 0.559 | 234.245 | 0.016 |
| Time‐to recurrence | ||||
| Model 4 | HR | 95% CI | p‐value | |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 1.06 | 0.188 | 5.982 | 0.948 |
| Wedge resection | 1.146 | 0.239 | 5.494 | 0.864 |
| Solid size, mm | ||||
| Size < 6 mm | 1 (ref) | |||
| Size ≥ 6 mm | 2.319 | 0.547 | 9.84 | 0.254 |
| Time‐to recurrence | ||||
| Model 5 | HR | 95% CI | p‐value | |
| Surgery | ||||
| Lobectomy | 1 (ref) | |||
| Segmentectomy | 3.882 | 0.641 | 23.519 | 0.141 |
| Wedge resection | 1.258 | 0.27 | 5.867 | 0.751 |
| Stage | ||||
| Stage IA1 | 1 (ref) | |||
| Stage IA2 | 0.841 | 0.005 | 22.722 | 0.599 |
| Stage IA3 | 62.01 | 2.837 | 855.185 | <0.001 |
Abbreviations: CI, confidence interval; HR, hazard ratio.
The incremental benefit of additional parameters was assessed using C‐statistics as shown in Table 4. With regard to disease recurrence, the benefits of tumor size (model 2) and stage (model 5) were significant as compared with the surgical procedure (model 1) (C‐index: 0.718 vs. 0.516, and 0.740 vs. 0.516, respectively; all p < 0.05).
TABLE 4.
C‐statistics for the prediction of disease recurrence
| C‐statistics for model with disease recurrence | |||
|---|---|---|---|
| Model | C‐index | Difference (95% CI) | Model comparison p‐value |
| Model 1: Surgery | 0.516 | NA | NA |
| Model 2: Surgery + tumor size | 0.718 | 0.202 (−0.015, 0.419) | 0.041 |
| Model 3: Surgery + tumor volume | 0.565 | 0.049 (−0.018, 0.117) | 0.754 |
| Model 4: Surgery + solid size | 0.523 | 0.007 (−0.075, 0.089) | 0.871 |
| Model 5: Surgery + stage | 0.740 | 0.224 (−0.079, 0.527) | 0.032 |
Note: Model comparison between Model 1 vs. Model 2, Model 1 vs. Model 3, Model 1 vs. Model 4 and Model 1 vs. Model 5.
When analyzing the recurrence outcomes among patients according to surgical procedures, the log‐rank test revealed no significant difference in RFS among the three groups (i.e., lobectomy, segmentectomy, and wedge resection; p = 0.99) (Figure 2).
FIGURE 2.
Time to recurrence in patients with adenocarcinoma presented as subsolid nodule stratified according to surgical procedure
DISCUSSION
In this study, we found that radiologically subsolid lung cancer in patients measuring less than 3 cm had an excellent surgical outcome regardless of surgical procedures, subsolid nodule subtype and solid component size. In addition, the TTR was not significantly different among the various surgical procedures (i.e., whether the patients underwent lobectomy, segmentectomy, or wedge resection). The findings in this study may help to guide surgical procedure selection in patients with clinical stage IA adenocarcinoma observed as subsolid nodules.
On the basis of the current evidence, the standard surgical treatment for primary lung cancer is still lobectomy, even though several trials to date have explored the use of sublobar resection for lung cancer. 7 , 8 , 9 , 16 , 17 , 18 One previous study using a national cancer database in the United States demonstrated that patients who underwent sublobar resection for stage IA NSCLC had poorer oncological outcomes. 19 On the other hand, a previous meta‐analysis demonstrated that patients with tumors measuring less than 2 cm located peripherally with favorable histopathology and with GGN on CT imaging might be candidates for sublobar resection instead of lobectomy. 20 Our study results were consistent with these findings. In our study, there was no recurrence among patients with tumors that were smaller than 2 cm regardless of surgical procedures, subsolid nodule subtype and solid component size. We found that tumor size larger than 2 cm and stage IA3 were independent risk factors of disease recurrence in patients with clinical stage IA subsolid adenocarcinoma.
Regarding part‐solid tumors, several studies have previously demonstrated that solid component size correlates more accurately with tumor invasiveness and prognosis than maximum tumor size. 4 , 21 , 22 Currently, the size of the solid component is applied to the category T stage for part‐solid lung cancers according to the eighth edition of the TNM classification scheme of lung cancer because the solid component is regarded as the invasive component. 23 However, our study showed that solid component size was not an independent predictor of tumor recurrence. Our results appear to be inconsistent with the results of several previous studies. 4 , 21 , 22 The reason why our results were different from previous studies may be related to our exclusion of pure solid tumor when considering the effect of solid component size. Although the solid component in a PSN by CT has a greater chance of having an invasive component on histological examination, the solid area could also represent a benign scar or a fibrous scar. 24 In addition, managing PSNs with several solid components can be a challenge because there is currently no consensus regarding how the solid components of these lesions should be measured.
There is still no strong evidence based on a randomized controlled trial for the extent of surgical resection for subsolid nodules. However, the results of this study validate and support the NCCN guideline (version 5, 2020) recommendation to guide surgical procedure selection in patients with clinical stage IA adenocarcinoma observed as subsolid nodules.
We acknowledge that there are some limitations and biases in our study. First, this study did not proceed with a randomized controlled investigation. For surgical methods, patients were not evenly assigned to lobectomy, segmentectomy, or wedge resection. In addition, the nodal sampling was not uniformly performed in each center. In the lobectomy and segmentectomy groups, all patients underwent mediastinal lymph node dissection. However, in the wedge resection group, 24 (34.2%) patients did not undergo mediastinal lymph node dissection. Second, the recurrence rate was very small. Only nine patients experienced disease recurrence. Therefore, depending on the recurrence rate, these results may be affected. To reduce the bias from low recurrence rate, we applied Firth correction when calculating 95% CI. Third, there was not enough follow‐up time after surgery to evaluate overall survival. The median follow‐up period was 5.01 years (interquartile range: 4.33–5.45 years). In this study, we evaluated the TTR instead of overall survival because in stage I disease more patients died from causes other than from cancer during the follow‐up period.
In conclusion, radiologically subsolid lung adenocarcinoma measuring <3 cm could be candidates for sublobar resection instead of lobectomy. In our study, subsolid lung cancer measuring smaller than 3 cm had excellent surgical outcome regardless of surgical procedures, subsolid nodule subtype and solid component size. In addition, the TTR was not significantly different among the various surgical procedures of lobectomy, segmentectomy, or wedge resection in patients with clinical stage IA adenocarcinoma observed as subsolid nodules. While these results need to be replicated in larger randomized controlled studies, our results validate subjects eligible for sublobar resection recommended by NCCN 2020 guideline and provide the surgeon with a rationale for choosing a less‐extensive surgical alternative for clinical stage IA adenocarcinomas observed as subsolid nodules without compromising patient outcomes.
CONFLICT OF INTEREST
All authors have no conflicts of interest to declare.
ACKNOWLEDGMENTS
This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (grant number: 2018R1D1A1B07043364).
Im DJ, Lee SM, Han K, et al. Predictive factors of recurrence after resection of subsolid clinical stage IA lung adenocarcinoma. Thoracic Cancer. 2021;12:941–948. 10.1111/1759-7714.13876
Funding information National Research Foundation of Korea (NRF), Grant/Award Number: grant number: 2018R1D1A1B07043364
REFERENCES
- 1. Boiselle PM. Computed tomography screening for lung cancer. JAMA. 2013;309:1163–70. [DOI] [PubMed] [Google Scholar]
- 2. Aberle DR, Abtin F, Brown K. Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial. J Clin Oncol. 2013;31(8):1002–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Pedersen JH, Saghir Z, Wille MM, Thomsen LH, Skov BG, Ashraf H. Ground‐glass opacity lung nodules in the era of lung cancer CT ccreening: radiology, pathology, and clinical management. oncology (Williston Park). 2016;30:266–74. [PubMed] [Google Scholar]
- 4. Tsutani Y, Miyata Y, Nakayama H, Okumura S, Adachi S, Yoshimura M, et al. Prognostic significance of using solid versus whole tumor size on high‐resolution computed tomography for predicting pathologic malignant grade of tumors in clinical stage IA lung adenocarcinoma: a multicenter study. J Thorac Cardiovasc Surg. 2012;143:607–12. [DOI] [PubMed] [Google Scholar]
- 5. Hung JJ, Jeng WJ, Hsu WH, Chou TY, Huang BS, Wu YC. Predictors of death, local recurrence, and distant metastasis in completely resected pathological stage‐I non‐small‐cell lung cancer. J Thorac Oncol. 2012;7:1115–23. [DOI] [PubMed] [Google Scholar]
- 6. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 nonesmall‐cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60:615–22. [DOI] [PubMed] [Google Scholar]
- 7. Sim HJ, Choi SH, Chae EJ, Kim HR, Kim YH, Kim DK, et al. Surgical management of pulmonary adenocarcinoma presenting as a pure ground‐glass nodule. Eur J Cardiothorac Surg. 2014;46:632–6. [DOI] [PubMed] [Google Scholar]
- 8. Tsutani Y, Miyata Y, Nakayama H, Okumura S, Adachi S, Yoshimura M, et al. Appropriate sublobar resection choice for ground glass opacity‐dominant clinical stage IA lung adenocarcinoma: wedge resection or segmentectomy. Chest. 2014;145:66–71. [DOI] [PubMed] [Google Scholar]
- 9. Cho JH, Choi YS, Kim J, Kim HK, Zo JI, Shim YM. Long‐term outcomes of wedge resection for pulmonary ground‐glass opacity nodules. Ann Thorac Surg. 2015;99:218–22. [DOI] [PubMed] [Google Scholar]
- 10. Naidich DP, Bankier AA, MacMahon H, Schaefer‐Prokop CM, Pistolesi M, Goo JM, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner society. Radiology. 2013;266:304–17. [DOI] [PubMed] [Google Scholar]
- 11. MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner society. Radiology. 2017;284:228–43. [DOI] [PubMed] [Google Scholar]
- 12. Park CH, Hur J, Lee SM, Lee JW, Hwang SH, Seo JS, et al. Lipiodol localization for ground‐glass opacity minimal surgery: rationale and design of the LOGIS trial. Contemp Clin Trials. 2015;43:194–9. [DOI] [PubMed] [Google Scholar]
- 13. Goldstraw P, Chansky K, Crowley J, Rami‐Porta R, Asamura H, Eberhardt WEE, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:39–51. [DOI] [PubMed] [Google Scholar]
- 14. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Kang L, Chen W, Petrick NA, Gallas BD. Comparing two correlated C indices with right‐censored survival outcome: a one‐shot nonparametric approach. Stat Med. 2014;34:685–703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Crabtree T, Puri V, Timmerman R, Fernando H, Bradley J, Decker PA, et al. Treatment of stage I lung cancer in high‐risk and inoperable patients: comparison of prospective clinical trials using stereotactic body radiotherapy (RTOG 0236), sublobar resection (ACOSOG Z4032), and radiofrequency ablation (ACOSOG Z4033). J Thorac Cardiovasc Surg. 2013;145:692–9. [DOI] [PubMed] [Google Scholar]
- 17. Wolf AS, Richards WG, Jaklitsch MT, Gill R, Chirieac LR, Colson YL, et al. Lobectomy versus sublobar resection for small (2 cm or less) non‐small cell lung cancers. Ann Thorac Surg. 2011;92:1819–23. [DOI] [PubMed] [Google Scholar]
- 18. Altorki NK, Yip R, Hanaoka T, Bauer T, Aye R, Kohman L, et al. Sublobar resectionis equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules. J Thorac Cardiovasc Surg. 2014;147:754–62. [DOI] [PubMed] [Google Scholar]
- 19. Khullar OV, Liu Y, Gillespie T, Higgins KA, Ramalingam S, Lipscomb J, et al. Survival after sublobar resection versus lobectomy for clinical stage IA lung cancer: an analysis from the National Cancer Data Base. J Thorac Oncol. 2015;10:1625–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Cao C, Chandrakumar D, Gupta S, et al. Could less be more?‐a systematic review and meta‐analysis of sublobar resections versus lobectomy for non‐small cell lung cancer according to patient selection. Lung Cancer. 2015;89:121–32. [DOI] [PubMed] [Google Scholar]
- 21. Maeyashiki T, Suzuki K, Hattori A, Matsunaga T, Takamochi K, Oh S. The size of consolidation on thin‐section computed tomography is a better predictor of survival than the maximum tumour dimension in resectable lung cancer. Eur J Cardiothorac Surg. 2013;43:915–8. [DOI] [PubMed] [Google Scholar]
- 22. Aokage K, Miyoshi T, Ishii G, Kusumoto M, Nomura S, Katsumata S, et al. Clinical and pathological staging validation in the eighth edition of the TNM classification for lung cancer: correlation between solid size on thin‐section computed tomography and invasive size in pathological findings in the new T classification. J Thorac Oncol. 2017;12:1403–12. [DOI] [PubMed] [Google Scholar]
- 23. Travis WD, Asamura H, Bankier AA, Beasley MB, Detterbeck F, Flieder DB, et al. The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part‐solid tumors in the forthcoming eighth edition of the TNM classification of lung lung cancer. J Thorac Oncol. 2016;11:1204–23. [DOI] [PubMed] [Google Scholar]
- 24. Aokage K, Miyoshi T, Ishii G, Kusumoto M, Nomura S, Katsumata S, et al. Influence of ground glass opacity and the corresponding pathological findings on survival in patients with clinical stage I non‐small cell lung cancer. J Thorac Oncol. 2018;13:533–42. [DOI] [PubMed] [Google Scholar]