The adrenal gland, which has a rich vascular supply, is a common site of metastasis from primary tumors such as those of the lung, kidney, breast, colon, and skin, particularly malignant melanoma (1). The prevalence of adrenal metastasis in autopsy studies of patients with extra-adrenal malignancies has been reported to range from 3.1% to 27% (1, 2). Although adrenal metastasis generally represents an advanced stage of disease and is often managed with systemic therapy or palliative care, previous reports have demonstrated that adrenalectomy may confer long-term survival benefits in carefully selected patients (3-6). According to the recent clinical practice guidelines jointly issued by the American Association of Clinical Endocrinology and the American Association of Endocrine Surgeons (AACE/AAES), surgical management of metastatic adrenal tumor should be individualized based on factors such as primary tumor type, timing of metastasis (synchronous or metachronous), disease-free interval, and tumor size (7). However, definite criteria for surgical indications and prognostic factors associated with postoperative survival have not yet been established.

The optimal surgical approach for metastatic adrenal tumors also remains controversial. While the remarkable advancement of minimally invasive techniques has established laparoscopic adrenalectomy as the standard treatment for benign adrenal tumors (8, 9), evidence regarding its use for metastatic adrenal tumors is mixed. Several studies have reported that laparoscopic adrenalectomy can achieve oncological outcomes and complication rates comparable to open adrenalectomy in appropriately selected patients (3, 10, 11). In contrast, open adrenalectomy remains preferred for large tumors, suspected local invasion, or aggressive primary malignancies, owing to concerns about tumor rupture and incomplete resection associated with laparoscopic procedures (12, 13).

Given these uncertainties, this study aimed to retrospectively evaluate the perioperative and survival outcomes of adrenalectomy for adrenal metastases at our institution and to identify prognostic factors that may help guide the selection of an appropriate surgical approach.

Study design and patients. This retrospective study included 30 patients who underwent adrenalectomy for metastatic adrenal tumors at Shiga University of Medical Science Hospital between November 2006 and March 2025. This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Shiga University of Medical Science Hospital (No. R2019-240). Patients who underwent concurrent adrenalectomy and ipsilateral nephrectomy for primary renal cell carcinoma were excluded. Adrenal metastasis was diagnosed by computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) and was confirmed by histopathological examination of the resected specimens.

Clinical data was obtained from institutional medical records. The following variables were reviewed: age, sex, body mass index (BMI), adrenal tumor size, tumor laterality, primary tumor type, interval from the initial diagnosis of primary tumor to adrenal metastasis, timing of adrenal metastasis (synchronous or metachronous), presence of extra-adrenal metastasis before or at the time of adrenalectomy, surgical approach (open, transperitoneal laparoscopic, or retroperitoneal laparoscopic), operative time, blood loss, conversion to open surgery, perioperative complications, length of postoperative hospital stay, surgical margin status, recurrence (locoregional or distant), and survival outcomes.

Definitions and outcome measures. Synchronous metastasis was defined as metastasis detected within six months after the initial diagnosis of the primary tumor, whereas metachronous metastasis was defined as metastasis detected more than six months after the primary tumor diagnosis. The surgical approach was determined through discussion among the surgical team based on each patient’s clinical characteristics and tumor findings. Extended adrenalectomy was defined as adrenalectomy combined with resection of adjacent organs. Postoperative complications occurring within 30 days after adrenalectomy were classified as Clavien–Dindo grade 2 or higher, and major complications were defined as grade 3 or higher. Follow-up protocols after adrenalectomy were not standardized across departments; however, most patients underwent periodic surveillance, primarily with CT imaging at 3-6-month intervals. The primary outcome was overall survival (OS), defined as the time from adrenalectomy to death or last follow-up.

Statistical analysis. Continuous variables are expressed as median values with interquartile ranges (IQR), and categorical variables as numbers and percentages. To evaluate the influence of tumor size on perioperative and survival outcomes, patients were stratified into two groups according to tumor diameter (<5 cm vs. ≥5 cm). Differences between these groups were assessed using the Mann–Whitney U-test or Fisher’s exact test, as appropriate. Survival curves were generated using the Kaplan–Meier method and compared between the two tumor-size groups using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors for OS. A p-value <0.05 was considered statistically significant. All statistical analyses were performed using EZR version 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R version 4.5.1 (The R Foundation for Statistical Computing, Vienna, Austria).

Patient characteristics. A total of 30 patients who underwent adrenalectomy for metastatic adrenal tumors were included. The baseline clinical characteristics are summarized in Table I. The median age was 67 years [interquartile range (IQR)=62-74], and 27 patients (90%) were male. The median body mass index (BMI) was 22.4 kg/m² (IQR=21.0-24.3). The median tumor size was 2.6 cm (IQR=2.2-4.3). Sixteen patients (53%) had right-sided tumors. The most common primary malignancies were lung cancer (n=13, 44%) and renal cell carcinoma (n=10, 33%), followed by sarcoma (n=3, 10%), esophageal cancer (n=2, 7%), malignant melanoma (n=1, 3%), and unknown primary (n=1, 3%). The median interval from the initial diagnosis of the primary malignancy to adrenal metastasis was 18 months (IQR=5-48). Eight patients (27%) had synchronous and 22 (73%) had metachronous metastases. 10 patients (33%) had a history of prior extra-adrenal metastasis, and five (17%) had concurrent extra-adrenal metastasis at the time of adrenalectomy. The median follow-up period after adrenalectomy was 26 months (IQR=10-90).

Perioperative and pathological outcomes. Perioperative and pathological outcomes are summarized in Table II. Of the 30 patients, 28 (93%) underwent laparoscopic adrenalectomy, including 24 (80%) transperitoneal and four (13%) retroperitoneal approaches, while two (7%) underwent open adrenalectomy. Conversion to open surgery was required in two patients (7%) because of intraoperative bleeding or dense adhesions. The median operative time was 209 min (IQR=173-314), and median blood loss 30 ml (IQR=0-100). Extended adrenalectomy was performed in six patients (20%) due to tumor invasion or severe adhesions, including single-organ resection in four (13%) and multi-organ resection in two (7%). Resected organs included the kidney, liver, spleen, pancreas, and lymph nodes. Intraoperative complications occurred in six patients (20%), including liver injury in three (10%), diaphragm injury in two (7%), and tumor capsule rupture in one (3%). 30-day postoperative complications occurred in five patients (17%), including adrenal insufficiency in two (7%), pneumonia in one (3%), pancreatic fistula in one (3%), and ischemic colitis in one (3%) (Table III). No major complications were observed. The median postoperative hospital stay was six days (IQR=5-10). Positive surgical margins were found in four patients (13%) (Table II).

To assess the impact of tumor size on perioperative outcomes, we compared patients with tumors <5 cm and ≥5 cm. Patients with tumors ≥5 cm had significantly longer operative time (186 vs. 344 min; p=0.012) and greater blood loss (10 vs. 250 ml; p=0.017). The rate of the extended adrenalectomy (12% vs. 50%; p=0.035) and open conversion (0% vs. 50%; p=0.012) were also higher in the ≥5 cm group. Intraoperative complications (20% vs. 67%; p<0.001) and 30-day postoperative complications (8% vs. 50%; p=0.041) were significantly more frequent in the ≥5 cm group. The median postoperative hospital stay was significantly longer in the ≥5 cm group (5 vs. 12 days; p=0.031). Although the rate of positive surgical margins tended to be higher in the ≥5 cm group (8% vs. 33%), the difference was not statistically significant (p=0.169).

Overall survival and prognostic factor. Over a median follow-up period of 26 months (IQR=10-90), locoregional recurrence was observed in four patients (13%) and distant recurrence in 14 (47%). Nine patients (30%) died of disease or other causes. The median OS for the entire cohort was 130 months [95% confidence interval (CI)=30-not reached]. The 1-, 2-, 5-, and 10-year OS rates were 88%, 79%, 68%, and 62%, respectively (Figure 1A). Patients with tumors ≥5 cm had significantly poorer OS compared with those with tumors <5 cm (5-year OS rate, 44% vs. 76%; median OS, 30 months vs. not reached; log-rank p=0.02) (Figure 1B). In univariate analysis, tumor size ≥5 cm was significantly associated with worse OS [hazard ratio (HR)=4.531; 95%CI=1.128-18.21; p=0.033). In multivariate analysis including tumor size ≥5 cm, extra-adrenal metastasis at adrenalectomy and positive surgical margin, tumor size ≥5 cm remained an independent predictor of poor OS (HR=4.985; 95%CI=1.033-24.06; p=0.045) (Table IV).

Metastatic adrenal tumors exhibit substantial clinical variability, complicating treatment selection. Several reports, including a recent comprehensive review (14), suggest that surgical resection may be beneficial in selected patients with isolated adrenal metastasis. Nevertheless, clear criteria for candidate selection and operative approach remain undefined. In this study, we retrospectively analyzed 30 patients who underwent adrenalectomy for metastatic adrenal tumors and evaluated clinical outcomes. The median OS of 130 months observed in our cohort was notably longer than those of 29-63 months reported in previous studies (4, 15, 16). The median tumor size in prior reports ranged from 2.8 to 5.6 cm (3, 17, 18), whereas in our study, it was relatively small at 2.6 cm, which may have contributed to the favorable survival outcomes. Perioperative outcomes were also satisfactory, with an open conversion rate of 7% and a 30-day postoperative complication rate of 10%, both of which were better than previously reported open conversion rates of 9-11% and 30-day postoperative complication rates of 10-40% (6, 10, 18, 19). However, patients with larger tumors experienced significantly longer operative time, increased intraoperative blood loss, and prolonged hospitalization, along with higher rates of conversion to open surgery and perioperative complications. These findings indicate that tumor size is a major determinant of surgical invasiveness in adrenalectomy for metastatic disease.

Regarding prognostic factors, tumor size ≥5 cm emerged as an independent predictor of poor OS in our multivariate analysis. The clinical relevance of this cutoff is supported by prior retrospective evidence: Zerrweck et al. identified that 5 cm was the optimal threshold for predicting long-term survival based on receiver operating characteristic (ROC) analysis, and tumor size ≥5 cm remained independently associated with inferior outcomes in their multivariate model (20). Additional studies have similarly demonstrated that larger tumor size correlates with worse oncological outcome (4, 11, 18). Tumor size is also closely related to surgical difficulty. The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines emphasize tumor size as a key determinant of operative invasiveness, noting longer operative times for adrenal tumors >5 cm (21). Consistent with these reports, our findings showed that tumors ≥5 cm were associated with prolonged operative time, greater blood loss, and higher perioperative morbidity. Other previously suggested prognostic factors – such as primary tumors other than renal cell carcinoma, synchronous metastasis, presence of extra-adrenal disease, and positive surgical margin (4, 11, 18, 20, 22) – did not reach statistical significance in our cohort. Collectively, existing evidence and our results underscore tumor size as a clinically meaningful parameter influencing both surgical complexity and postoperative survival in patients undergoing adrenalectomy for metastatic disease.

Laparoscopic adrenalectomy has become the standard approach for benign adrenal tumors with advances in minimally invasive surgery (7, 23). Accumulating evidence also suggests that laparoscopic adrenalectomy may be a feasible option for selected patients with metastatic adrenal tumors. For metastatic lesions, laparoscopic adrenalectomy has been associated with reduced perioperative morbidity and shorter hospital stay compared with open surgery (24). Furthermore, overall survival has been reported to be comparable between laparoscopic and open adrenalectomy for metastatic adrenal tumors without adjacent organ invasion (11). Nevertheless, concerns persist regarding tumor spillage, port-site metastasis, and incomplete resection, particularly in large tumors or those with suspected local invasion (13, 25-27). Therefore, open adrenalectomy continues to be recommended in such situations. In our cohort, tumors ≥5 cm more frequently required complex surgical procedures, often because of dense adhesions to adjacent organs. Although tumor size is a major contributor to surgical complexity, recent evidence indicates that periadrenal tissue characteristics may also affect operative difficulty. Miyamoto et al. reported that higher Mayo Adhesive Probability (MAP) scores, reflecting adherent perinephric fat, were associated with longer operative time and increased technical difficulty in laparoscopic adrenalectomy (28). Considering these findings collectively, tumor size remains a practical and clinically meaningful indicator when selecting the surgical approach. Accordingly, laparoscopic adrenalectomy appears to be an appropriate option for tumors <5 cm, whereas open surgery may be considered for tumors ≥5 cm, depending on surgical complexity.

Study limitations. First, it is a retrospective analysis conducted at a single institution with a limited sample size. Second, the impact of systemic chemotherapy and radiotherapy for primary or metastatic lesions on survival outcomes was not fully evaluated. Third, the follow-up duration was short in some patients, which may limit the generalizability of our findings. In addition, the small number of events relative to covariates may reduce the stability of the multivariate analysis. Further multicenter collaborative studies are needed to establish optimal treatment strategies for metastatic adrenal tumors.

This study demonstrated that adrenalectomy for adrenal metastasis can provide favorable long-term survival in appropriately selected patients. Laparoscopic adrenalectomy is a useful minimally invasive option for tumors <5 cm. In contrast, tumors ≥5 cm are associated with greater surgical invasiveness and poorer prognosis, warranting careful selection of surgical candidates, including consideration of open adrenalectomy.

The Authors have no conflicts of interest to declare in relation to this study.

MN: conceptualization, data curation, formal analysis, methodology, resources, writing of the manuscript. KY: investigation, methodology, review and editing of the manuscript. TK: conceptualization, data curation. SK: data curation, resources. MN: data curation, resources. AW: data curation, resources. KK: investigation, resources. TY: investigation, resources. KJ: investigation, resources. SK: review and editing of the manuscript, study supervision.

The Authors have nothing to report.

During the preparation of this manuscript, a large language model (ChatGPT-5, OpenAI) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the data generation, statistical analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors.