Distinguishing Adrenal Metastases from Benign Lesions in NSCLC: The Value of Clinical and Radiological Parameters

doi:10.21203/rs.3.rs-8311183/v1

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Distinguishing Adrenal Metastases from Benign Lesions in NSCLC: The Value of Clinical and Radiological Parameters

https://doi.org/10.21203/rs.3.rs-8311183/v1

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Background

Lung cancer is the most prevalent malignancy worldwide and the leading cause of cancer-related deaths. The adrenal gland is a frequent site of metastasis in non-small cell lung cancer (NSCLC). The differentiation of adrenal metastases from benign lesions is imperative for accurate staging and treatment planning. Imaging methods such as FDG-PET/CT, CT, and MRI provide important diagnostic information; however, false negative and false positive results may occur with these methods. The employment of clinical, biochemical, and radiological predictors has the potential to enhance diagnostic precision.

Methods

A retrospective cross-sectional study was performed on NSCLC patients diagnosed between 2015 and 2025. From 2196 lung cancer cases, 121 patients who exhibited adrenal lesions on initial PET/CT scans but did not manifest extrathoracic metastases. Clinical data (age, sex, TN stage), biochemical markers (CEA, CA125) and radiological parameters (SUVmax, lesion size, laterality) were obtained. The relationship of these parameters with the presence of adrenal metastasis was systematically evaluated in order to identify potential predictors.

Results

Of 121 patients, 86 had adrenal metastases and 35 had benign adrenal lesions. Malignant lesions demonstrated significantly higher SUVmax, larger size, and elevated CEA and CA125 levels. ROC analysis revealed optimal cut-off values: SUVmax > 3.05 (AUC = 0.86, sensitivity 89%, specificity 69%), CEA > 4.45 ng/mL, CA125 > 24.5 U/mL, and lesion size > 14.5 mm. Multivariate regression identified N3 stage (OR = 12.75, p = 0.043), elevated CEA (OR = 1.02, p = 0.038), and lesion size (OR = 1.09, p = 0.037) as independent predictors of metastasis. Most patients with metastasis were diagnosed at advanced stages, with 91.9% being T3–4 or N2–3.

Conclusion

The present study demonstrates that SUVmax, lesion size, CEA, T stage, and N stage are significantly associated with adrenal metastasis in NSCLC. Integrated assessment of these clinical, biochemical, and radiological parameters can improve the differentiation of adrenal metastase from benign lesions, facilitating more accurate staging and treatment planning.

Non-small cell lung cancer

Adrenal Metastasis

PET/CT

SUVmax

Lung cancer remains the most frequently diagnosed malignancy worldwide, with an estimated Lung cancer remains the most frequently diagnosed malignancy worldwide, with an estimated 2.5 million new cases annually and continues to be the leading cause of cancer-related mortality (1). Histologically, it is broadly categorized as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the latter comprising adenocarcinoma, squamous cell carcinoma and large-cell carcinoma (2). NSCLC accounts for approximately 80–90% of all lung cancer cases. At presentation, only 15% of NSCLC patients are diagnosed at an early stage, 20–25% present with locally advanced disease and the majority, 55–60%, present with metastatic disease (3).

Therapeutic strategies in NSCLC are stage-dependent. In localized and locoregional stages, surgical resection remains the cornerstone of curative treatment in appropriately selected patients (4). Yet, high recurrence rates following surgery alone have prompted the integration of perioperative systemic therapies, including platinum-based chemotherapy, targeted therapies and immunotherapy, all of which have transformed outcomes in recent years (5–9). In locally advanced, non-resectable disease, concurrent chemoradiation followed by consolidation with durvalumab or osimertinib in epidermal growth factor receptor (EGFR)-mutant tumors represents the current standard of care (10, 11). By contrast, in metastatic disease, therapeutic intent is palliative—the aim is to extend survival and improve quality of life. Thus, accurate staging and precise identification of metastatic spread are of paramount clinical relevance.

The adrenal glands represent a frequent site of metastatic involvement in NSCLC, reported in approximately 16% of cases, after bone (34%), lung (32%) and brain (28%) (12). However, adrenal lesions identified during staging present a well-recognized diagnostic dilemma. While many correspond to true metastases, benign counterparts such as adenomas, hemorrhage, granulomatous disease, or primary adrenal tumors are also common. This distinction carries major therapeutic implications, particularly in patients without other extrathoracic disease, where a misclassification may alter staging, eligibility for curative surgery, or systemic treatment strategy.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is widely employed in staging and has demonstrated high diagnostic accuracy, with reported sensitivity and specificity approaching 90% and 97% for adrenal lesions, respectively (13). Nonetheless, pitfalls exist: false-negative findings may occur in small (< 10 mm), necrotic, indolent adenocarcinoma metastases, or early lesions, whereas false-positive uptake may be observed in lipid-poor adenomas, hemorrhagic nodules, adrenal hyperplasia, infections, or granulomatous disease (14, 15). Indeed, up to 5% of adenomas may demonstrate FDG uptake exceeding hepatic reference values, mimicking metastases (15). Similarly, computed tomography (CT) and magnetic resonance imaging (MRI) provide valuable morphological characterization, yet remain limited by occasional false-positive and false-negative interpretations (16–18). Although histopathology remains the diagnostic gold standard, biopsy is often restricted by procedural risks, technical limitations and clinical feasibility.

This clinical conundrum underscores the need for reliable non-invasive predictors. Integrative assessment combining imaging characteristics, biochemical parameters and tumor staging may offer enhanced diagnostic performance. Against this background, the present study sought to evaluate the predictive roles of SUVmax (Maximum Standardized Uptake Value) on PET/CT, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), adrenal lesion size and primary tumor T (tumor size and invasion stage) and N (lymph node spread) stage in differentiating benign adrenal lesions from true adrenal metastases in patients with NSCLC. By doing so, we aim to contribute to the refinement of a clinically applicable diagnostic algorithm for risk stratification and therapeutic decision-making.

This study was designed as a retrospective, cross-sectional analysis. Medical records of all patients diagnosed with lung cancer between 2015 and 2025 at our institution were systematically reviewed (n = 2,194). Among these, patients were eligible if they had a confirmed diagnosis of NSCLC and evidence of an adrenal lesion detected on initial PET/CT performed at the time of diagnosis, without any evidence of extrathoracic metastasis.

Adrenal lesions were defined as metastatic under one of the following conditions:

Histopathological confirmation of malignancy; or

Radiological features consistent with metastasis on CT and/or MRI; and

Radiological progression or regression during ≥ 6 months of imaging follow-up.

Lesions that demonstrated stability during follow-up were considered benign. Patients with SCLC, extrathoracic metastases or incomplete clinical, imaging and laboratory data were excluded.

A total of 121 patients meeting these criteria were included in the final analysis and their age, sex, primary tumor T and N stage, serum CEA and CA125 levels, adrenal lesion size, anatomical location and SUVmax were recorded.

Ethics approval

; The study protocol was reviewed and approved by the Atatürk University Non-Interventional Clinical Research Ethics Committee (decision no. B.30.2.ATA.0.01.00/758, dated 31 October 2025). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical Analysis

All statistical analyses were conducted using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). Categorical variables were reported as counts and percentages, with group comparisons performed using the Pearson chi-square test. Continuous variables were expressed as mean ± standard deviation (SD) or median (range), and compared using the Mann–Whitney U test.

The diagnostic value of SUVmax, CEA, CA125 and adrenal lesion size in differentiating malignant from benign lesions was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cut-off points determined by the Youden index. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of adrenal metastasis. P-value < 0.05 was considered statistically significant.

Between 2015 and 2025, a total of 2,194 patients were diagnosed with lung cancer in our center. Among these, 121 patients meeting the eligibility criteria were included in the final analysis. Of these, 86 patients (71.1%) had adrenal metastases and 35 patients (28.9%) had benign adrenal lesions. The patient selection flowchart is shown below (Fig. 1).

Baseline demographic and clinical characteristics of the included patients are summarized in Table 1.

Table 1

Baseline Demographic and Clinical Characteristics of The Study Population
Variable		Benign		Metastase
Variable		N (%)	Median (range)	N %	Median (range)
Sex	Male	31 (88,6%)		81 (94,2%)
Sex	Female	4 (1,4%)		5 (5,8%)
Lesion location	Bilateral	3 (8,6%)		26 (0,2%)
	Right	7 (20,0%)		17 (19,8%)
	Left	25 (71,4%)		43 (50,0%)
Histologic subtype	AC	14 (40,0%)		43 (50,0%)
	NOS	5 (14,3%)		12 (14,0%)
	SCC	16 (45,7%)		31 (36,0%)
Age			70 (42–88)		63 (26–82)
CA-125 (U/mL)			16 (4-1224)		41,50 (4,1-5600)
SUVmax			2,30 (1, 5–16)		5,75 (2,2–41,0)
CEA (ng/mL)			3 (1–62)		8,60 (0,6-1300)
Lesion size (mm)			13 (8–30)		20 (8–90)

AC: Adenocarsinoma; CA-125: Cancer antigen 125; CEA: Carcinoembryonic antigen; mm: millimeters ; ng/mL: nanograms per milliliter; NOS: Not Otherwise Specified; SCC: Squamous cell carcinoma; SUVmax: maximum standardized uptake value; U/mL: units per milliliter.

SUVmax, CEA, CA125 and lesion size parameters were compared between patients with adrenal metastases and those with benign lesions. SUVmax (p = 0.000), CEA (p < 0.01), CA125 (p < 0.01) and lesion size (p < 0.01) were found to be significantly higher in patients with adrenal metastases (Table 2).

Table 2

Comparison Of Suvmax, CEA, CA125 and Lesion Size Between Benign and Metastatic Adrenal Lesions
Parameter	Benign Lesions mean ± SD (range)	Metastatic Lesions mean ± SD (range).	p value
SUVmax	3.11 ± 2.52 (1.5–16.0)	8.90 ± 7.80 (2.2–41.0)	< 0.001**
CEA (ng/mL	8.96 ± 14.1 (1.0–62.0)	135.1 ± 275.6 (0.6–1300)	0.002**
CA125 (U/mL)	108 ± 250 (4–1244)	244 ± 733 (4.1–5600)	0.004**
Lesion size (mm)	16 ± 7 (8–30)	24 ± 15 (8–90)	0.003**
Statistical comparisons were performed using the Mann–Whitney U test. : p < 0.01. CA-125: Cancer antigen 125; CEA: Carcinoembryonic antigen; mm: millimeters; ng/mL: nanograms per milliliter; SUVmax: maximum standardized uptake value; U/mL: units per milliliter

ROC curve analysis demonstrated that these variables had moderate to high discriminatory capacity for differentiating adrenal metastases from benign adrenal lesions (Fig. 2).

SUVmax showed the highest diagnostic performance, with a cut-off value of 3.05 yielding an AUC of 0.86 (95% CI, 0.78–0.94), corresponding to 89% sensitivity and 69% specificity (Table 3).

Table 3

ROC Analysis of SUVmax, CEA, CA125 and Lesion Size For Differentiating Adrenal Metastases From Benign Lesions
Parameter	AUC (95% CI)	p-value	Sensitivity	Specificity	Cut-off value	PPV (%)	NPV (%)
SUVmax	0.86 (0.78–0.94)	< 0.001	0.89	0.69	3.05	87.4	70.6
CEA (ng/mL)	0.69 (0.59–0.80)	0.002	0.68	0.62	4.45	77.6	40.0
CA125 (U/mL)	0.67 (0.54–0.79)	0.006	0.69	0.66	24.5	80.5	45.5
Lesion size (mm)	0.71 (0.61–0.82)	0.001	0.75	0.62	14.5	80.0	46.3
AUC: Area Under The Curve; CA-125: Cancer antigen 125; CEA: Carcinoembryonic antigen; CI: confidence interval; mm: millimeters; ng/mL: nanograms per milliliter; NPV:Negative Predictive Value; PPV: Positive Predictive Value SUVmax: maximum standardized uptake value; U/mL: units per milliliter

The benign lesions and metastasis groups were compared in terms of T and N stage, together with SUVmax, CEA, CA125 levels and lesion size, based on the cut-off values obtained from the ROC analysis (Table 4).

Table 4

Comparison of T Stage, N Stage, SUVmax, Lesion Size, CEA, CA125 and Anatomical Location Between Benign and Metastatic Adrenal Lesions
Variable	Benign Lesions n (%)	Metastatic Lesions n (%)	p-value*
T stage			0.020
1	10 (28.6)	7 (8.1)
2	8 (22.9)	19 (22.1)
3	7 (20.0)	32 (37.2)
4	10 (28.6)	28 (32.6)
N stage			0.002
0	7 (20.0)	3 (3.5)
1	7 (20.0)	7 (8.1)
2	15 (42.9)	44 (51.2)
3	6 (17.1)	32 (37.2)
SUVmax			< 0.001
< 3.05	24 (68.6)	10 (11.6)
≥ 3.05	11 (31.4)	76 (88.4)
Lesion size (mm)			0.002
< 14.5	19 (54.3)	22 (25.6)
≥ 14.5	16 (45.7)	64 (74.4)
CEA (ng/mL)			0.039
< 4.45	18 (51.4)	27 (31.4)
≥ 4.45	17 (48.6)	59 (68.6)
CA125 (U/mL)			0.002
< 24.5	20 (57.1)	24 (37.9)
≥ 24.5	15 (42.9)	62 (62.1)
Location			0.032
Right	7 (20.0)	17 (19.8)
Left	25 (71.4)	43 (50.0)
Bilateral	3 (8.6)	26 (38.2)
;Pearson’s Chi-Square Test p value < 0.05 was considered significant* CA-125: Cancer antigen 125; CEA: Carcinoembryonic antigen; mm: millimeters; ng/mL: nanograms per milliliter; SUVmax: maximum standardized uptake value; U/mL: units per milliliter

As shown in Table 4, T stage (p = 0.020), N stage (p = 0.002), SUVmax (p < 0.001), CEA (p = 0.013) and CA125 (p = 0.001) demonstrated significant differences between the benign lesions and metastasis groups. In addition, it was observed that only 20% of both metastases and benign lesions were located on the right side, while 80% were left-sided or bilateral. Further stratification revealed that the prevalence of adrenal metastases was markedly higher in patients with advanced T3–T4 tumors and in those with N2–N3 nodal involvement. Notably, only 7 patients (8.1%) with adrenal metastases were in early stage (T1–2, N0–1), whereas the majority (91.9%) were classified as T3–4 or N2–3 (Table 5).

Table 5

Distribution of T and N stages in Patients With Adrenal Metastases
T stage	N0 n (%)	N1 n (%)	N2 n (%)	N3 n (%)	Total n (%)
T1	1 (1.2)	2 (2.3)	3 (3.5)	1 (1.2)	7 (8.1)
T2	2 (2.3)	2 (2.3)	8 (9.3)	7 (8.1)	19 (22.0)
T3	0 (0.0)	2 (2.3)	22 (25.6)	8 (9.3)	32 (37.2)
T4	0 (0.0)	1 (1.2)	11 (12.8)	16 (18.6)	28 (32.5)
Total	3 (3.5)	7 (8.1)	44 (51.1)	32 (37.2)	86 (100)

On univariate logistic regression, higher T stage, higher N stage, SUVmax, serum CEA, serum CA125 and larger adrenal lesion size were all significantly associated with adrenal metastasis (Table 6).

Table 6

Univariate and Multivariate Logistic Regression Analyses of Clinical Variables Predicting Adrenal Metastasis
Variable	Univariate OR (95% CI)	p-value	Multivariate OR (95% CI)	p-value
T stage		0.032		0.315
1 (ref)	Reference	—	Reference	—
2	3.39 (0.95–12.09)	0.060	2.85 (0.43–18.83)	0.277
3	6.53 (1.84–23.15)	0.004	5.03 (0.73–34.42)	0.099
4	4.00 (1.19–13.35)	0.024	1.77 (0.25–12.22)	0.562
N stage		0.006		0.306
0 (ref)	Reference	—	Reference	—
1	2.33 (0.42–12.91)	0.332	4.14 (0.29–58.05)	0.291
2	6.84 (1.56–29.88)	0.011	5.72 (0.53–61.90)	0.151
3	12.44 (2.48–62.20)	0.002	12.75 (0.87–186.24)	0.043
CEA (ng/mL)	1.02 (1.00–1.04)	0.049	1.02 (1.00–1.05)	0.038
CA125 (U/mL)	1.00 (0.99–1.01)	0.048	0.99 (0.99–1.01)	0.602
Lesion size (mm)	1.07 (1.02–1.13)	0.007	1.09 (1.06–1.19)	0.037
SUVmax	1.16 (1.03–1.30)	0.009	1.04 (0.95–1.13)	0.379
Model fit: −2 Log Likelihood = 80.38; Nagelkerke R² = 0.489.

CA-125: Cancer antigen 125; CEA: Carcinoembryonic antigen; mm: millimeters; ng/mL: nanograms per milliliter; SUVmax: maximum standardized uptake value; U/mL: units per milliliter

However, in multivariate analysis, N3 stage (OR 12.75; p = 0.043), elevated serum CEA (OR 1.02; p = 0.038) and adrenal lesion size (OR 1.09 per mm increase; p = 0.037) remained as independent predictors of malignant adrenal involvement. The multivariate logistic regression model explained approximately 48.9% of the variance in malignancy risk.

Lung cancer remains the most frequently diagnosed malignancy worldwide and the leading cause of cancer-related death (1). Adrenal involvement is identified in nearly 16% of patients with NSCLC (12). Despite advances in imaging, studies have shown that radiological methods for characterizing adrenal lesions may yield false-negative or false-positive results in up to 10% of cases (13, 17, 18). In our study, we demonstrated that SUVmax, N stage, T stage, CEA, CA125, and lesion size are important parameters in predicting whether an adrenal lesion represents metastasis or a benign process.

SUVmax is a metric that reflects tissue metabolic activity by measuring ^18F-FDG uptake on PET/CT. It is a well-established fact that tumour cells characteristically demonstrate elevated metabolic rates in comparison to normal tissue. Consequently, the presence of elevated SUVmax values is commonly associated with malignant disease (19). In the present cohort, SUVmax values were found to be significantly higher in patients with adrenal metastases compared with those with benign lesions. ROC analysis identified a cut-off of 3.05, which achieved an AUC of 0.86 with high sensitivity (89%) but only moderate specificity (69%). This finding aligns with the conclusions of previous studies in this field. Cho et al. demonstrated that a cut-off of 2.7 discriminated adrenal metastases with an area under the curve (AUC) of 0.94 (20), while Metser et al. described a threshold of 3.01 providing 98.5% sensitivity and 92% specificity (21). In univariate regression analysis, SUVmax was significantly associated with adrenal metastasis; however, it did not remain an independent predictor in the multivariate model, likely due to correlation with lesion size and N stage. When patients were stratified by the 3.05 threshold, 68.6% of those with SUVmax < 3.05 had benign lesions, whereas 88.4% of patients with SUVmax > 3.05 harbored metastases. These results confirm SUVmax as a strong predictive parameter, while also underscoring its limitations: approximately one-third of low-SUVmax lesions were later identified as early metastases or adenocarcinoma metastases with low FDG avidity (22).

CEA is a glycoprotein produced during intrauterine life that plays an important role in cell adhesion (23). While its use as a prognostic biomarker in colorectal cancer is well-documented, elevated CEA levels have also been associated with metastatic disease burden and the number of metastases in patients with lung cancer (24). In the present study, CEA levels were found to be significantly elevated in the metastasis group. ROC curve analysis indicated a cut-off value of 4.45 ng/mL, yielding moderate discriminatory capacity (AUC 0.69). Notwithstanding these limitations, regression analysis confirmed that elevated CEA was significantly associated with adrenal metastasis. This finding suggests that, while CEA alone is not a robust parameter for distinguishing metastasis from benign adrenal lesions, it may offer valuable complementary information when interpreted alongside clinical, radiological, and other biochemical parameters.

CA125 is a glycoprotein that is widely utilised as a prognostic biomarker, particularly in the context of gynaecological malignancies. Additionally, there have been suggestions that CA125 may be associated with metastatic disease in lung cancer (25). Nevertheless, the prognostic significance and diagnostic accuracy of the test for detecting metastasis in NSCLC remain uncertain. In the present study, CA125 levels were found to be elevated in the adrenal metastasis group in comparison with benign lesions. However, ROC curve analysis with a cut-off value of 24.5 U/mL demonstrated only limited sensitivity and specificity, indicating that CA125 has restricted value as a standalone parameter in distinguishing adrenal metastases from benign lesions.

The present study identified N stage as one of the strongest parameters for predicting adrenal metastasis. As demonstrated in Table 2, the distribution of T and N stages indicates that adrenal lesions detected in patients with T1–2 and N0–1 disease are more likely to be benign. Conversely, our logistic regression model demonstrated that adrenal lesions in patients with N3 stage carried a 12-fold higher risk of representing metastasis, which is a particularly striking finding. These results are consistent with those of previous studies suggesting that lymphatic dissemination plays a key role in the development of adrenal metastases in NSCLC (26).

Furthermore, adrenal lesion size was identified as a significant parameter for distinguishing between benign and metastatic lesions. In the present study, adrenal masses were found to be significantly larger in the metastasis group. Concurrent large series have similarly reported that malignant adrenal tumours tend to be larger than benign lesions (27). ROC analysis identified a cut-off value of 14.5 mm, above which the likelihood of metastasis increased approximately threefold. Nevertheless, the diagnostic performance of this threshold was found to be limited, exhibiting modest sensitivity and specificity. Furthermore, 25.6% of adrenal metastases in the present cohort measured less than 14.5 mm, emphasising that small lesions cannot be assumed to be benign. In accordance with the extant literature, the present findings suggest that larger adrenal size is a useful predictor for metastasis, yet small lesions also warrant careful evaluation (28).

The strengths of our study include the selection of a homogeneous cohort restricted to NSCLC histology, thereby providing a more specific and focused sample. Moreover, by excluding patients with extrathoracic metastases and evaluating only cases with adrenal lesions, we were able to investigate adrenal involvement in greater detail. Another salient strength is the integrated evaluation of clinical, biochemical, and imaging parameters, which collectively furnish a more comprehensive evaluation of metastasis risk.

However, it is important to acknowledge several limitations of this study. The retrospective, single-centre design and the relatively limited sample size may restrict the generalizability of the findings. Furthermore, not all adrenal lesions were subject to pathological confirmation, and reliance on radiological follow-up in some cases may have introduced misclassification bias.

In summary, SUVmax, serum CEA, lesion size, and T and N stage were all significantly associated with the presence of adrenal metastases in patients with NSCLC. For patients with suspicious adrenal lesions, the combined assessment of these clinical, biochemical and imaging parameters provides a more reliable means of differentiating metastasis from benign lesions, thereby enhancing diagnostic accuracy and supporting more appropriate treatment planning.

• 18F-FDG

Fluorine-18 fluorodeoxyglucose

• AUC

Area under the curve

• CA125

Cancer antigen 125

• CEA

Carcinoembryonic antigen

• CI

Confidence interval

• CT

Computed tomography

• EGFR

Epidermal growth factor receptor

• MRI

Magnetic resonance imaging

• N

Nodal stage

• NSCLC

Non-small cell lung cancer

• OR

Odds ratio

• PET/CT

Positron emission tomography/computed tomography

• ROC

Receiver operating characteristic

• SCLC

Small cell lung cancer

• SD

Standard deviation

• SUVmax

Maximum standardized uptake value

• T

Tumor stage

Ethics approval

The study protocol was reviewed and approved by the Atatürk University Non-Interventional Clinical Research Ethics Committee (decision no. B.30.2.ATA.0.01.00/758, dated 31 October 2025). Given the retrospective nature of the study and the anonymized use of patient data, the requirement for individual informed consent was waived by the ethics committee. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing Interests

The authors declare that they have no competing interests.

Conflict of interest

Authors report no Conflict of Interest in any product mentioned or concept discussed in this article.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author Contribution

Conception and design: AAÇ, ZH, MEB, AT, YES, MB, SBT(II) Administrative support: AAÇ, ZH, MEB, AT, MB, (III) Provision of study materials or patients: AAÇ, ZH, MEB, AT, YES, MB, SBT(IV) Collection and assembly of data: AAÇ, ZH, MEB, AT, YES, (V) Data analysis and interpretation: AAÇ, ZH, MEB, AT, YES, MB, SBT(VI) Manuscript writing: All authors(VII) Final approval of manuscript: All authors

Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229–263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.
Luo G, Zhang Y, Rumgay H, Morgan E, Langselius O, Vignat J, Colombet M, Bray F. Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: a population-based study. Lancet Respir Med. 2025;13(4):348–363. 10.1016/S2213-2600(24)00428-4. Epub 2025 Feb 3. PMID: 39914442.
Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383(7):640–9. 10.1056/NEJMoa1916623. PMID: 32786189; PMCID: PMC8577315.
Alduais Y, Zhang H, Fan F, Chen J, Chen B. Non-small cell lung cancer (NSCLC): A review of risk factors, diagnosis, and treatment. Med (Baltim). 2023;102(8):e32899. 10.1097/MD.0000000000032899. PMID: 36827002; PMCID: PMC11309591.
Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T, LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552–9. 10.1200/JCO.2007.13.9030. Epub 2008 May 27. PMID: 18506026.
Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H. IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344–1357. 10.1016/S0140-6736(21)02098-5. Epub 2021 Sep 20. Erratum in: Lancet. 2021;398(10312):1686. doi: 10.1016/S0140-6736(21)02135-8. PMID: 34555333.
Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD. KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023;389(6):491–503. 10.1056/NEJMoa2302983. Epub 2023 Jun 3. PMID: 37272513; PMCID: PMC11074923.
Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N. CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386(21):1973–1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11. PMID: 35403841; PMCID: PMC9844511.
Herbst RS, Wu YL, John T, Grohe C, Majem M, Wang J, Kato T, Goldman JW, Laktionov K, Kim SW, Yu CJ, Vu HV, Lu S, Lee KY, Mukhametshina G, Akewanlop C, de Marinis F, Bonanno L, Domine M, Shepherd FA, Urban D, Huang X, Bolanos A, Stachowiak M, Tsuboi M. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023;41(10):1830–1840. doi: 10.1200/JCO.22.02186. Epub 2023 Jan 31. Erratum in: J Clin Oncol. 2023;41(22):3877. 10.1200/JCO.23.00658. PMID: 36720083; PMCID: PMC10082285.
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Özgüroğlu M. PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919–29. 10.1056/NEJMoa1709937. Epub 2017 Sep 8. PMID: 28885881.
Lu S, Kato T, Dong X, Ahn MJ, Quang LV, Soparattanapaisarn N, Inoue T, Wang CL, Huang M, Yang JC, Cobo M, Özgüroğlu M, Casarini I, Khiem DV, Sriuranpong V, Cronemberger E, Takahashi T, Runglodvatana Y, Chen M, Huang X, Grainger E, Ghiorghiu D, van der Gronde T, Ramalingam SS. LAURA Trial Investigators. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC. N Engl J Med. 2024;391(7):585–97. 10.1056/NEJMoa2402614. Epub 2024 Jun 2. PMID: 38828946.
Tamura T, Kurishima K, Nakazawa K, Kagohashi K, Ishikawa H, Satoh H, Hizawa N. Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 2015;3(1):217–21. 10.3892/mco.2014.410. Epub 2014 Sep 4. PMID: 25469298; PMCID: PMC4251107.
Boland GW, Dwamena BA, Jagtiani Sangwaiya M, Goehler AG, Blake MA, Hahn PF, Scott JA, Kalra MK. Characterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance. Radiology. 2011;259(1):117–26. 10.1148/radiol.11100569. Epub 2011 Feb 17. PMID: 21330566.
Kandathil A, Wong KK, Wale DJ, Zatelli MC, Maffione AM, Gross MD, Rubello D. Metabolic and anatomic characteristics of benign and malignant adrenal masses on positron emission tomography/computed tomography: a review of literature. Endocrine. 2015;49(1):6–26. 10.1007/s12020-014-0440-6. Epub 2014 Oct 2. PMID: 25273320.
Sundin A. Imaging of adrenal masses with emphasis on adrenocortical tumors. Theranostics. 2012;2(5):516–22. 10.7150/thno.3613. Epub 2012 May 17. PMID: 22737189; PMCID: PMC3364557.
Blake MA, Cronin CG, Boland GW. Adrenal imaging. AJR Am J Roentgenol. 2010;194(6):1450-60. 10.2214/AJR.10.4547. Erratum in: AJR Am J Roentgenol. 2012;198(5):1232. PMID: 20489083.
Caoili EM, Korobkin M, Francis IR, Cohan RH, Platt JF, Dunnick NR, Raghupathi KI. Adrenal masses: characterization with combined unenhanced and delayed enhanced CT. Radiology. 2002;222(3):629 – 33. 10.1148/radiol.2223010766. PMID: 11867777.
Dunnick NR, Korobkin M. Imaging of adrenal incidentalomas: current status. AJR Am J Roentgenol. 2002;179(3):559 – 68. 10.2214/ajr.179.3.1790559. PMID: 12185019.
Boellaard R, O'Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, Oyen WJ, Kotzerke J, Hoekstra OS, Pruim J, Marsden PK, Tatsch K, Hoekstra CJ, Visser EP, Arends B, Verzijlbergen FJ, Zijlstra JM, Comans EF, Lammertsma AA, Paans AM, Willemsen AT, Beyer T, Bockisch A, Schaefer-Prokop C, Delbeke D, Baum RP, Chiti A, Krause BJ. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181–200. 10.1007/s00259-009-1297-4. PMID: 19915839; PMCID: PMC2791475.
Cho AR, Lim I, Na II, Choe du H, Park JY, Kim BI, Cheon GJ, Choi CW, Lim SM. Evaluation of Adrenal Masses in Lung Cancer Patients Using F-18 FDG PET/CT. Nucl Med Mol Imaging. 2011;45(1):52–8. 10.1007/s13139-010-0064-6. Epub 2010 Nov 11. PMID: 24899978; PMCID: PMC4042950.
Metser U, Miller E, Lerman H, Lievshitz G, Avital S, Even-Sapir E. 18F-FDG PET/CT in the evaluation of adrenal masses. J Nucl Med. 2006;47(1):32–7. PMID: 16391184.
Sung YM, Lee KS, Kim BT, Choi JY, Chung MJ, Shim YM, Yi CA, Kim TS. (18)F-FDG PET versus (18)F-FDG PET/CT for adrenal gland lesion characterization: a comparison of diagnostic efficacy in lung cancer patients. Korean J Radiol 2008 Jan-Feb;9(1):19–28. doi: 10.3348/kjr.2008.9.1.19. PMID: 18253072; PMCID: PMC2627169.
Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem. 2008;283(23):15647–55. 10.1074/jbc.M800543200. Epub 2008 Mar 27. PMID: 18375392; PMCID: PMC2414264.
Wang J, Chu Y, Li J, Wang T, Sun L, Wang P, Fang X, Zeng F, Wang J, Zeng F. The clinical value of carcinoembryonic antigen for tumor metastasis assessment in lung cancer. PeerJ. 2019;7:e7433. 10.7717/peerj.7433. PMID: 31410309; PMCID: PMC6689222.
Wang CF, Peng SJ, Liu RQ, Yu YJ, Ge QM, Liang RB, Li QY, Li B, Shao Y. The Combination of CA125 and NSE Is Useful for Predicting Liver Metastasis of Lung Cancer. Dis Markers. 2020;2020:8850873. 10.1155/2020/8850873. PMID: 33376560; PMCID: PMC7746448.
Bazhenova L, Newton P, Mason J, Bethel K, Nieva J, Kuhn P. Adrenal metastases in lung cancer: clinical implications of a mathematical model. J Thorac Oncol. 2014;9(4):442–6. 10.1097/JTO.0000000000000133. PMID: 24736064; PMCID: PMC3989547.
Song JH, Chaudhry FS, Mayo-Smith WW. The incidental adrenal mass on CT: prevalence of adrenal disease in 1,049 consecutive adrenal masses in patients with no known malignancy. AJR Am J Roentgenol. 2008;190(5):1163-8. 10.2214/AJR.07.2799. PMID: 18430826.
Lenert JT, Barnett CC Jr, Kudelka AP, Sellin RV, Gagel RF, Prieto VG, Skibber JM, Ross MI, Pisters PW, Curley SA, Evans DB, Lee JE. Evaluation and surgical resection of adrenal masses in patients with a history of extra-adrenal malignancy. Surgery. 2001;130(6):1060-7. 10.1067/msy.2001.118369. PMID: 11742339.

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Distinguishing Adrenal Metastases from Benign Lesions in NSCLC: The Value of Clinical and Radiological Parameters

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