Is the consolidation-to-tumor ratio an independent prognostic factor in clinical T1 stage lung adenocarcinoma radiologically manifesting as a subsolid nodule?—a retrospective cohort study

Abstract

Background

Previous studies indicate that preoperative radiological features, particularly the consolidation-to-tumor ratio (CTR), are associated with prognosis in stage IA lung adenocarcinoma. However, the prognostic value of different CTR thresholds remains controversial in lung adenocarcinoma manifesting as subsolid nodules (SSNs), and whether CTR is an independent prognostic factor has not yet been clarified. Our study aimed to investigate prognostic differences among T1 stage SSN lung adenocarcinoma patients with varying CTR thresholds, maximum solid component diameters (MCDs), and maximum tumor diameters (MTDs). We also sought to explore the independent prognostic value of CTR in this group.

Methods

This retrospective study included patients with cT1 stage SSN lung adenocarcinoma who underwent radical resection at The First Affiliated Hospital of Shandong First Medical University between December 2017 and December 2021. The Kaplan-Meier was used to estimate overall survival (OS) and recurrence-free survival (RFS), with the log-rank test comparing survival curves between groups. Firth’s penalized Cox regression analysis was employed to identify independent prognostic factors for T1 stage SSN lung adenocarcinoma.

Results

A total of 509 SSNs from 493 patients were analyzed [230 pure ground-glass nodules (pGGNs) and 279 partly solid nodules (PSNs)], with a median follow-up duration of 50.3 months (range, 3.5–86.0 months). Kaplan-Meier analysis showed that the 5-year OS rate for T1 stage SSN lung adenocarcinoma patients was 98.6% [95% confidence interval (CI): 97.4–99.9%], with a 5-year RFS rate of 98.3% (95% CI: 97.0–99.7%). Among SSN lung adenocarcinomas, only the difference in OS between the 0< CTR ≤0.25 and 0.25< CTR <1 groups was statistically significant. Regarding RFS, statistically significant differences were observed between different CTR threshold groups, MCD groups classified according to the 8^th edition tumor-node-metastasis (TNM) staging, and MTD groups. In PSN lung adenocarcinoma, only RFS showed statistical differences between the CTR group (cutoff 0.5) and the MCD group (cutoff 20 mm). Stratified analysis revealed that MCD and MTD stratification within the 0.25< CTR <1 group had no significant impact on OS, and similarly, MCD and MTD stratification within the 0.5< CTR <1 group showed no statistical differences for RFS. Multivariate analysis indicated that lobectomy was an independent protective factor for OS in T1 stage SSN lung adenocarcinoma, while preoperative carcinoma embryonic antigen (CEA) levels were independent risk factors for RFS in this group.

Conclusions

CTR >0.25, MCD >10 mm, and MTD >20 mm are associated with a poorer prognosis in T1 stage SSN lung adenocarcinoma. However, neither CTR, MCD, nor MTD is not an independent prognostic factor for the group; preoperative CEA levels represent more stable and independent prognostic predictors than CTR.

Highlight box.

Key findings

• In cT1 stage subsolid nodule (SSN) lung adenocarcinoma, a consolidation-to-tumor ratio (CTR) >0.25, a maximum solid component diameter (MCD) >10 mm, and a maximum tumor diameter (MTD) >20 mm are associated with poorer overall survival (OS) and recurrence-free survival (RFS).

• Multivariate analysis revealed that CTR, MCD, and MTD are not independent prognostic factors; instead, the surgical approach is an independent predictor for OS, and preoperative carcinoembryonic antigen (CEA) level is an independent predictor for RFS.

What is known and what is new?

• The optimal prognostic cutoff value for the CTR in early-stage lung adenocarcinoma is controversial, with studies proposing various thresholds. Furthermore, the value of CTR as an independent prognostic factor, distinct from other tumor size measurements, remains debated.

• This study newly finds that while a CTR >0.25 is significant, CTR itself is not an independent prognostic factor when considered with CEA. Additionally, within specific CTR ranges, MCD/MTD stratification provides no additional prognostic information.

What is the implication, and what should change now?

• The clinical role of the CTR requires redefinition, shifting from a potential standalone prognostic factor to a subsidiary risk-stratification tool. Prognosis should depend less on a specific CTR cutoff and more on robust biomarkers like preoperative CEA. While valuable for suggesting invasiveness and guiding surgical extent, CTR should not be the primary predictor of survival. Thus, for cT1 SSN lung adenocarcinoma, clinical guidelines should integrate serum biomarkers with imaging features rather than prioritizing imaging alone.

Introduction

Lung cancer is the most prevalent malignant tumor in the world in terms of incidence and mortality, according to GLOBOCAN 2022 (1), of which non-small cell lung cancer (NSCLC) accounts for 80–85%, with lung adenocarcinoma being its primary subtype (2). The widespread application of low-dose computed tomography (LDCT) screening has significantly improved the detection rate of early-stage subsolid nodule (SSN) lung adenocarcinoma (3), which presents on computed tomography (CT) as focal ground-glass opacity with or without solid components. Since the Japanese Clinical Oncology Group (JCOG0201) study prospectively validated that the consolidation-to-tumor ratio (CTR)—the ratio of the largest solid component to the tumor’s maximum diameter on high-resolution CT (HRCT)—can predict the radiological definition of pathologic non-invasive stage IA lung adenocarcinoma (4), many thoracic surgeons have observed that for resectable NSCLC, CTR and solid component size better predict prognosis than maximum tumor size (5-7).

However, the clinical value of CTR as a prognostic marker for SSN lung adenocarcinoma remains significantly controversial. Concerning risk stratification thresholds, many studies have reported varying findings about the prognostic significance of different CTR cutoff values (8-11). Furthermore, while some studies suggest that CTR is an independent prognostic factor in SSN lung adenocarcinoma (10,12,13), others argue that it is not an independent predictor and that its prognostic value has been superseded by the 8^th edition tumor-node-metastasis (TNM) staging system (14-16).

Therefore, the purpose of this study is to analyze the prognostic differences among patients with T1 stage SSN lung adenocarcinoma based on different CTR thresholds, maximum solid component diameters (MCDs), and maximum tumor diameters (MTDs). It also aims to further explore the independent prognostic value of CTR for T1 stage SSN lung adenocarcinoma. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2192/rc).

Methods

Patients

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The First Affiliated Hospital of Shandong First Medical University (No. 2024S943). Informed consent was waived as this was a retrospective study. Clinical T1 stage SSN lung adenocarcinoma undergoing radical resection at our institution between December 2017 and December 2021 was retrospectively included. Inclusion criteria: (I) preoperative lung CT demonstrating cT1 stage (according to TNM 8^th edition) SSN; and (II) pathologically confirmed primary lung adenocarcinoma. Exclusion criteria: (I) prior needle biopsy or neoadjuvant therapy before CT examination; (II) poor CT image quality, such as severe respiratory and metal artifacts; and (III) incomplete clinical and pathological data.

Radiological evaluation

All patients underwent non-contrast chest CT scans prior to surgery. The CT images in this study were acquired using various CT scanners, including Insurance CT (Philips, Amsterdam, The Netherlands), uCT550 (United Imaging, Shanghai, China), Revolution 256 (GE Healthcare, Chicago, IL, USA), uCT960+ (United Imaging), and Discovery CT750 HD (GE Healthcare). All examinations were performed with patients in a standardized supine position with arms raised. The scanning range extended from the thoracic inlet to the costophrenic angle, ensuring full coverage of the entire chest. Scanning parameters were set as follows: tube voltage of 120 kV, tube current using automatic tube current modulation technology (range, 100–300 mA), matrix 512×512, and slice thicknesses of 0.625, 1, and 1.25 mm.

Two radiologists (X.Z., with 5 years of diagnostic experience; D.W., with 10 years of diagnostic experience) measured the maximum diameter of the SSN lung adenocarcinoma and the maximum diameter of its solid component on a single axial slice using standard lung windows [window width 1,600 Hounsfield units (HU), window shift −600 HU]. Measurement discrepancies were resolved through discussion and consensus. Intraclass correlation coefficient (ICC) was used to assess measurement consistency between the two radiologists, with an ICC greater than 0.80 considered indicative of good measurement repeatability. The ICC values for measuring the maximum diameter of SSN lung adenocarcinoma and its solid component were 0.976 [95% confidence interval (CI): 0.972–0.980] and 0.978 (95% CI: 0.975–0.982), respectively.

SSN includes pure ground-glass nodules (pGGNs) and partly solid nodules (PSNs). Ground-glass refers to areas with density higher than lung tissue but insufficient to obscure overlying vessels and bronchi, while PSN combines ground-glass density with solid components (17). CTR refers to the ratio of the maximum diameter of the solid component to the maximum diameter of the entire tumor in the cT1 stage SSN lung adenocarcinoma on HRCT lung window images (CTR =0 for pGGN; CTR ranges from 0 to 1 for PSN). Using 0.25 as the CTR threshold, PSN exhibits four morphological types (Figure 1). In our study, CTR was calculated by dividing the mean size of the solid component by the mean MTD, as measured by two radiologists. When the solid component was irregular or multiple, multiplanar reconstruction was used, and only the largest diameter was analyzed.

Figure 1.

Four PSNs classified using a CTR threshold of 0.25. (A) PSN in the left upper lobe (0< CTR ≤0.25). (B) PSN in the left upper lobe (0.25< CTR ≤0.5). (C) PSN in the right upper lobe (0.5< CTR ≤0.75). (D) PSN in the right upper lobe (0.75< CTR <1). CTR, consolidation-to-tumor ratio; PSN, partly solid nodules.

Pathological evaluation

According to the multidisciplinary classification criteria for lung adenocarcinoma jointly established by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS), postoperative pathological diagnosis is primarily categorized as follows: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAD). IAD can be further subdivided based on its predominant histological growth pattern into the following subtypes: lepidic, acinar, papillary, micropapillary, solid, and invasive mucinous adenocarcinoma. The predominant histological pattern refers to the most abundant component among all components (assessed semi-quantitatively in 5% increments), without requiring that component to constitute 50% or more of the tissue (18).

Surgical and follow-up protocol

All lung resection procedures were carried out by thoracic surgeons at The First Affiliated Hospital of Shandong Medical University. Surgical methods included anatomical lobectomy and sublobar resection (wedge resection and anatomical segmentectomy). Anatomical lobectomy remains the standard treatment for early-stage lung cancer in this study. However, sublobar resection is considered for peripheral, T1a–b N0 SSN NSCLC cases where a ≥2 cm lung parenchymal margin can be maintained. The specific surgical approach depends on the patient’s functional status, the size and location of the SSN adenocarcinoma tumor, and the surgeon’s expertise with the technique. All patients undergoing resection received either systematic lymph node dissection or lobar-specific dissection.

Follow-up occurred every 3 months for the first 2 years postoperatively, with chest CT scans at 3–6-month intervals. Subsequently, follow-up occurred every 6 months for 3 years, with annual chest CT scans. Imaging techniques, including brain CT or magnetic resonance imaging (MRI) and bone-emission CT (ECT), were employed to detect recurrence based on patient status. The follow-up endpoints in our study were overall survival (OS) and recurrence-free survival (RFS). OS was defined as the time from the date of surgery to death from any cause or the last follow-up date (10 March 2025). RFS was defined as the time from the date of surgery to tumor recurrence, appearance of a new primary lung cancer, or the last follow-up date (10 March 2025).

Statistical analysis

SPSS (version 22.0) and R software (version 4.4.1) were used for statistical analysis. Continuous variables were presented as mean ± standard deviation (SD) and compared using the Wilcoxon rank-sum test. Categorical variables were presented as frequency and percentage and compared using the Pearson Chi-squared test. Patient data were censored for those alive or lost to follow-up as of 10 March 2025. OS and RFS were estimated using the Kaplan-Meier method, with intergroup differences determined by the log-rank test. Cox regression analysis was first performed to identify variables with P<0.1 for inclusion in the multivariate Cox regression analysis, aiming to control the number of variables and exclude unstable ones. Firth’s penalized Cox proportional hazards model was used to identify significant prognostic factors for OS and RFS in stage T1 SSN lung adenocarcinoma. P values were adjusted using the Holm-Bonferroni method, and a two-sided P value <0.05 was considered statistically significant.

Results

Following strict inclusion and exclusion criteria, 509 SSNs from 493 patients with cT1 stage SSN lung adenocarcinoma were ultimately enrolled in this study, comprising 230 pGGNs and 279 PSNs. Preoperative clinical imaging and postoperative pathological characteristics of these patients were compared and analyzed, as shown in Table 1. Patients with PSN lung adenocarcinoma were older than those with pGGN (59.64±9.72 vs. 54.86±11.10 years, P<0.001) and had higher preoperative carcinoma embryonic antigen (CEA) levels (2.37±1.65 vs. 1.94±1.27 ng/mL, P<0.001). Additionally, preoperative imaging characteristics (MTD, mean CT value, lobulated sign, and number of imaging signs), pathological tumor (pT), surgical approach, and postoperative histopathological type differed between the two groups. Lobulated sign refers to a nodule surface characterized by multiple irregularly curved areas resembling flower petals. Imaging signs included air bronchogram, pleural indentation, and vessel convergence. Notably, female patients (66%) and non-smokers (83%) constituted a high proportion among all T1 stage SSN lung adenocarcinomas, whereas this trend showed no significant statistical difference in the pGGN and PSN groups.

Table 1. Baseline characteristics.

Variables	Overall (n=509)	pGGN (n=230)	PSN (n=279)	P value†
Gender				0.97
Male	173 [34]	78 [34]	95 [34]
Female	336 [66]	152 [66]	184 [66]
Age (years)	57.48±10.62	54.86±11.10	59.64±9.72	<0.001
Tumor location				0.47
Left upper lobe	129 [25]	67 [29]	62 [22]
Left lower lobe	67 [13]	30 [13]	37 [13]
Right upper lobe	172 [34]	71 [31]	101 [36]
Right middle lobe	35 [7]	16 [7]	19 [7]
Right lower lobe	106 [21]	46 [20]	60 [22]
MCD (mm)	5.35±6.41	0.00±0.00	9.76±5.64	<0.001
MTD (mm)	15.56±6.09	12.66±4.82	17.95±6.00	<0.001
Average CT value (HU)	−504.31±143.40	−588.13±102.28	−435.22±135.48	<0.001
Lobulated sign				<0.001
No	294 [58]	200 [87]	94 [34]
Yes	215 [42]	30 [13]	185 [66]
Imaging signs				<0.001
<2	352 [69]	221 [96]	131 [47]
≥2	157 [31]	9 [4]	148 [53]
CEA (ng/mL)	2.18±1.51	1.94±1.27	2.37±1.65	<0.001
BMI (kg/m2)	24.46±3.09	24.42±2.90	24.49±3.24	0.95
Smoking history				0.08
No	424 [83]	199 [87]	225 [81]
Yes	85 [17]	31 [13]	54 [19]
Tumor history				0.76
No	440 [86]	200 [87]	240 [86]
Yes	69 [14]	30 [13]	39 [14]
Pathologic type				<0.001
AIS/MIA	329 [65]	212 [92]	117 [42]
IAD	180 [35]	18 [8]	162 [58]
pN				0.25
pN0	505 [99]	230 [100]	275 [99]
pN1	2 [0]	0 [0]	2 [1]
pN2	2 [0]	0 [0]	2 [1]
pT				<0.001
pTis	235 [46]	179 [78]	56 [20]
pT1mi	92 [18]	31 [13]	61 [22]
pT1a	35 [7]	8 [3]	27 [10]
pT1b	111 [22]	10 [4]	101 [36]
pT1c	36 [7]	2 [1]	34 [12]
Surgery				<0.001
Sublobectomy	254 [50]	143 [62]	111 [40]
Lobectomy	255 [50]	87 [38]	168 [60]

Data are presented as n [%] or mean ± SD. ^†, Pearson’s Chi-squared test or Wilcoxon rank sum test. AIS, adenocarcinoma in situ; BMI, body mass index; CEA, carcinoembryonic antigen; HU, Hounsfield units; IAD, invasive adenocarcinoma; MCD, maximum solid component diameter; MIA, minimally invasive adenocarcinoma; MTD, maximum tumor diameter; pGGN, pure ground-glass nodule; pN, pathological node; PSN, partly solid nodule; pT, pathological tumor; SD, standard deviation.

The median follow-up period after surgery was 50.3 months (range, 3.5–86.0 months). Kaplan-Meier analysis showed that the 5-year OS rate for T1 stage SSN lung adenocarcinoma patients was 98.6% (95% CI: 97.4–99.9%), and the 5-year RFS rate was 98.3% (95% CI: 97.0–99.7%). Among T1 stage SSN lung adenocarcinoma, the difference in OS (Figure 2) was statistically significant only between the 0< CTR ≤0.25 and 0.25< CTR <1 groups [5-year OS rate: 100.0% (95% CI: 100.0–100.0%) vs. 97.3% (95% CI: 94.9–99.8%), P=0.02] (Figure 2A). There was no statistically significant difference in OS among other CTR thresholds, MCD, or MTD groups (Figure 2B-2G). As for RFS (Figure 3), only a mild statistical significance was observed between the 0< CTR ≤0.25 and 0.25< CTR <1 groups (P=0.047) (Figure 3A). While there was a significant difference in RFS between the two CTR groups divided by the CTR =0.5 threshold [5-year RFS rate: 99.7% (95% CI: 99.1–100.0%) vs. 95.4% (95% CI: 91.6–99.3%), P<0.001] (Figure 3B), whereas the CTR =0.75 cutoff showed no significant difference (Figure 3C). Significant statistical differences were also observed between MCD and MTD groups stratified by 10- and 20-mm thresholds (Figure 3D-3G), except for the MTD group using the 10 mm cutoff (Figure 3F). We also investigated the prognostic differences among different CTR, MCD, and MTD for T1 stage PSN lung adenocarcinoma. In PSN lung adenocarcinoma, neither CTR nor MCD and MTD showed significant statistical differences in OS (Figure 4). Only the CTR group divided by a threshold of 0.5 showed a significant difference in 5-year RFS rate [100.0% (95% CI: 100.0–100.0%) vs. 95.4% (95% CI: 91.6–99.3%), P=0.02] and between MCD groups with a 20 mm threshold [5-year RFS rate: 97.6% (95% CI: 95.3–99.9%) vs. 95.2% (95% CI: 86.6–100.0%), P=0.048] (Figure 5). The risk tables for each survival curve are shown from top to bottom as depicted in Figures 2H,3H,4H,5H.

Figure 2.

OS in T1 stage SSN lung adenocarcinoma with varying CTR, MCD, and MTD. (A-C) CTR groups. (D,E) MCD groups. (F,G) MTD groups. (H) Number of risks. CTR, consolidation-to-tumor ratio; MCD, maximum solid component diameter; MTD, maximum tumor diameter; OS, overall survival; SSN, subsolid nodule.

Figure 3.

RFS in T1 stage SSN lung adenocarcinoma with varying CTR, MCD, and MTD. (A-C) CTR groups. (D,E) MCD groups. (F,G) MTD groups. (H) Number of risks. CTR, consolidation-to-tumor ratio; MCD, maximum solid component diameter; MTD, maximum tumor diameter; RFS, recurrence-free survival; SSN, subsolid nodule.

Figure 4.

OS of T1 stage PSN lung adenocarcinoma patients stratified by different CTR, MCD, and MTD. (A-C) CTR groups. (D,E) MCD groups. (F,G) MTD groups. (H) Number of risks. CTR, consolidation-to-tumor ratio; MCD, maximum solid component diameter; MTD, maximum tumor diameter; OS, overall survival; PSN, partly solid nodules.

Figure 5.

RFS of T1 stage PSN lung adenocarcinoma patients stratified by different CTR, MCD, and MTD. (A-C) CTR groups. (D,E) MCD groups. (F,G) MTD groups. (H) Number of risks. CTR, consolidation-to-tumor ratio; MCD, maximum solid component diameter; MTD, maximum tumor diameter; PSN, partly solid nodules; RFS, recurrence-free survival.

To explore the correlation and independent roles of CTR, MCD, and MTD in prognostic prediction and to identify the most dominant prognostic factor, we conducted stratified analyses and multivariate Cox regression analyses. We stratified the group with a significantly poor prognosis. Results showed that stratification by MCD and MTD within the 0.25< CTR <1 group had no significant impact on OS for T1 stage SSN lung adenocarcinoma (Figure 6A,6B). Similarly, stratification by MCD and MTD within the 0.5< CTR <1 group did not yield statistically significant differences in RFS for T1 stage SSN lung adenocarcinoma (Figure 6C,6D). Differences between groups with different CTR thresholds are shown in Table S1.

Figure 6.

Survival analysis stratified by MCD and MTD within the 0.25< CTR <1 and 0.5< CTR <1 groups. MCD (A) and MTD (B) were stratified for OS analysis within the 0.25< CTR <1 group. MCD (C) and MTD (D) were stratified for RFS analysis within the 0.5< CTR <1 group. CTR, consolidation-to-tumor ratio; MCD, maximum solid component diameter; MTD, maximum tumor diameter; OS, overall survival; RFS, recurrence-free survival.

After univariate Cox regression analysis, for OS, five variables were ultimately included: average CT value [hazard ratio (HR) =1.006; 95% CI: 1.001–1.011; P=0.02], MCD (HR =1.100; 95% CI: 0.990–1.222; P=0.08), surgery (ref: sublobectomy) (HR =0.230; 95% CI: 0.032–1.624; P=0.08), age (HR =1.079; 95% CI: 0.985–1.181; P=0.08), and CTR (HR =9.901; 95% CI: 0.581–168.665; P=0.08). For RFS, eight variables were ultimately included: CEA (HR =1.488; 95% CI: 1.278–1.732; P<0.001), MCD (HR =1.148; 95% CI: 1.051–1.254; P=0.002), average CT value (HR =1.006; 95% CI: 1.001–1.010; P=0.01), CTR (HR =17.858; 95% CI: 1.381–230.957; P=0.01), lobulated sign (ref: no) (HR =6.476; 95% CI: 1.007–41.633; P=0.01), MTD (HR =1.134; 95% CI: 1.016–1.266; P=0.02), pathologic type (ref: AIS/MIA) (HR =4.294; 95% CI: 0.908–20.304; P=0.04), and imaging signs (ref: <2) (HR =3.402; 95% CI: 0.820–14.112; P=0.07). We established separate multivariate models for OS and RFS, incorporating CTR (but excluding MCD and MTD) to avoid multicollinearity. Firth-penalized Cox regression analysis indicated that only the surgical approach was an independent factor for OS in T1 stage SSN lung adenocarcinoma, with lobectomy being a protective factor relative to sublobar resection (HR =0.12, 95% CI: 0.01–0.77, P=0.02; HR =0.15, 95% CI: 0.01–0.83, P=0.03) (Table 2). For RFS in the T1 stage SSN lung adenocarcinoma, only CEA was an independent risk factor (HR =1.43, 95% CI: 1.18–1.72, P=0.001; HR =1.36, 95% CI: 1.14–1.58, P=0.002) (Table 3).

Table 2. Multivariate analysis of OS in SSN lung adenocarcinoma (firth-penalized Cox regression).

Variables	OS (not include CTR)			OS (include CTR)
	HR (95% CI)	P value		HR (95% CI)	P value
Average CT value	1.01 (0.99–1.01)	0.07		1.01 (0.99–1.01)	0.08
MCD	1.06 (0.93–1.22)	0.37		–	–
Surgery (ref: sublobectomy)	0.12 (0.01–0.77)	0.02*		0.15 (0.01–0.83)	0.03*
Age	1.03 (0.95–1.13)	0.53		1.03 (0.96–1.14)	0.44
CTR	–	–		2.04 (0.08–81.48)	0.67

*, statistical significance. CI, confidence interval; CT, computed tomography; CTR, consolidation-to-tumor ratio; HR, hazard ratio; MCD, maximum solid component diameter; OS, overall survival; SSN, subsolid nodule.

Table 3. Multivariate analysis of RFS in SSN lung adenocarcinoma (firth-penalized Cox regression).

Variables	RFS (not include CTR)			RFS (include CTR)
	HR (95% CI)	P value		HR (95% CI)	P value
CEA	1.43 (1.18–1.72)	0.001*		1.36 (1.14–1.58)	0.002*
MCD	1.08 (0.88–1.35)	0.47		–	–
Average CT value	1.00 (0.99–1.01)	0.59		1.00 (0.99–1.01)	0.44
CTR	–	–		1.29 (0.01–186.80)	0.92
Lobulated sign (ref: no)	2.16 (0.26–26.4)	0.48		3.19 (0.41–38.70)	0.28
MTD	1.08 (0.87–1.27)	0.45		–	–
Pathologic type (ref: AIS/MIA)	1.15 (0.13–10.4)	0.90		1.47 (0.16–14.90)	0.74
Imaging signs (ref: <2)	0.19 (0.02–2.05)	0.17		0.51 (0.09–3.78)	0.48

*, statistical significance. AIS, adenocarcinoma in situ; CEA, carcinoembryonic antigen; CI, confidence interval; CT, computed tomography; CTR, consolidation-to-tumor ratio; HR, hazard ratio; MCD, maximum solid component diameter; MIA, minimally invasive adenocarcinoma; MTD, maximum tumor diameter; RFS, recurrence-free survival; SSN, subsolid nodule.

Additionally, we evaluated risk factors associated with the aggressiveness of early-stage SSN lung adenocarcinoma. When using univariate and multivariate logistic regression analysis, we found that SSN lung adenocarcinoma patients with a history of smoking [odds ratio (OR) =2.27; 95% CI: 1.12–4.60; P=0.02], tumors located in the left lower lobe (OR =3.70; 95% CI: 1.50–9.18; P=0.005), larger tumor size (OR =1.16; 95% CI: 1.10–1.22; P<0.001), and higher CTR (OR =126.23; 95% CI: 30.32–525.45; P<0.001) were independently associated with invasive lung adenocarcinoma (Table S2).

Discussion

This study was designed to investigate the impact of different CTR thresholds, MCD, and MTD on the prognosis of T1 stage SSN lung adenocarcinoma, as well as their independent predictive value. Through the retrospective analysis of 509 cT1 stage SSN lung adenocarcinoma in our hospital, we found that patients with CTR >0.25, MCD >10 mm, and MTD >20 mm had a poorer prognosis. However, neither CTR, MCD, nor MTD was an independent prognostic factor for cT1 stage SSN lung adenocarcinoma.

Our preliminary analysis revealed that CTR, MCD, and MTD at different thresholds showed significant differences in OS and/or RFS for cT1 stage SSN lung adenocarcinoma. The stratified analysis revealed that after restricting the CTR range (0.25–1 or 0.5–1), MCD and MTD failed to provide additional prognostic information. Multivariate Cox regression analysis ultimately revealed that only surgery (ref: sublobectomy) was an independent predictor of OS, while CEA was an independent predictor of RFS. Our retrospective analysis identified lobectomy as an independent factor associated with improved OS, a finding that contrasts with results from randomized controlled trials (RCTs) such as CALGB 140503 (19) and JCOG0802 (20). We attribute this discrepancy primarily to differences in study design and patient selection rather than to a true disparity in surgical efficacy. Whereas the referenced RCTs applied strict eligibility criteria—including peripheral location, tumor size ≤2 cm, and clinical stage T1aN0—and random allocation to directly compare treatment effects, our observational study reflects real-world clinical practice. Recent findings by Seder et al. (21) further affirm that such data provide valid insights into prognostic variations across actual treatment pathways, reinforcing the contextual relevance of our findings. In addition to surgical approach, preoperative CEA levels are also a key prognostic variable. Our findings align with those of Sun et al. (22), indicating that elevated preoperative CEA levels remain an independent risk factor for recurrence in NSCLC patients even after radical surgery, predicting a higher risk of postoperative recurrence.

The concept of CTR was first proposed by Japanese researchers Ohde et al. (23), and it subsequently attracted widespread attention in the field of medical imaging. Current studies mainly focus on evaluating the pathological invasiveness of early-stage lung cancer (24,25), predicting lymph node metastasis risk (26,27), guiding surgical planning (28-30), and assessing patient prognosis (10,31). This study aims to investigate the impact of CTR and other factors on the prognosis of T1 stage SSN lung adenocarcinoma. However, the role of CTR in prognosis remains controversial. First, multiple studies have identified CTR as an independent prognostic factor for clinically IA stage lung adenocarcinoma. Yet, Kim et al. (15) and Nakada et al. (16) suggest CTR was not an independent prognostic factor for lung adenocarcinoma. They noted that current clinical T staging is applicable to SSN lung adenocarcinoma. Ye et al. (32) further concluded that neither CTR nor MCD could predict the prognosis of PSN lung adenocarcinoma, consistent with our findings. While Nakao et al. (33) believed that subdividing PSN based on CTR (using 0.5 as the cutoff) and MCD was necessary to assess its prognosis. Second, regarding the optimal CTR threshold, discrepancies exist across studies. Ito et al. (9) suggested that 0.25 was used as the cutoff value, indicating that T1N0 stage lung adenocarcinoma patients with CTR ≤0.25 had a better prognosis. In contrast, Yoon et al. (11), Zhai et al. (12), and Jing et al. (31) suggested that widening the threshold to 0.75 could still effectively identify stage IA patients with a favorable prognosis. Our findings support the view of Ito et al. (9), demonstrating that patients with CTR ≤0.25 showed significantly better RFS and OS compared to those with CTR >0.25. This difference implies that the prognostic value of CTR may be influenced by clinical factors such as study population characteristics, imaging assessment criteria, and follow-up duration. Furthermore, the lack of a unified measurement consensus for solid components in PSN that are difficult to accurately measure may also be a key reason for the discrepancies observed across studies. Notably, the findings of this study agree with those of Sun et al. (34) and Qi et al. (35), all indicating that preoperative CEA levels was also an important prognostic indicator for clinical T1 stage lung cancer, particularly significantly correlated with RFS.

The findings of this study provide important implications for clinical practice on SSN. Although CTR is a significant indicator for predicting pathological invasiveness in SSN lung adenocarcinoma, it is not an independent prognostic factor worthy of clinicians’ attention compared to preoperative CEA levels. CTR effectively predicts invasiveness mainly because the solid components observed on imaging often correlate with pathologically invasive lesions (36). Prognosis depends not only on tumor aggressiveness but also on factors such as tumor stage, treatment modality, molecular-genetic characteristics, and patient systemic status. CTR primarily reflects local tumor invasion characteristics and represents only one of many influencing factors.

There are some limitations in this study. First, due to the limited number of outcome events, propensity score matching (PSM) was not performed, and the relevant findings should be regarded as preliminary exploratory results. Second, the retrospective design resulted in incomplete preoperative positron emission tomography (PET)-CT data, which may affect the comprehensive assessment of SSN lung adenocarcinoma characteristics. Finally, pathological indicators such as STAS were not systematically analyzed; future prospective studies are needed to clarify their relationship with imaging features and prognosis.

Conclusions

In summary, in the T1 stage SSN lung adenocarcinoma, patients with CTR >0.25 and MCD >10 mm, and MTD >20 mm indicate a poorer prognosis. However, CTR, MCD, and MTD are not independent prognostic factors for T1 stage SSN lung adenocarcinoma; preoperative CEA levels are more stable and independent prognostic predictors than CTR.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The First Affiliated Hospital of Shandong First Medical University (No. 2024S943), and informed consent was waived due to the retrospective study.

Data Sharing Statement

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DOI: 10.21037/jtd-2025-aw-2192