Metastasis to the adrenal glands: An update

Abstract

Adrenal metastases are increasingly detected during cancer staging and post-treatment surveillance, yet diagnostic and therapeutic pathways remain heterogeneous. Distinguishing benign adrenal lesions from metastases is clinically important when the lesion is solitary, potentially oligometastatic, or may alter systemic treatment strategy. This narrative review summarizes evidence on epidemiology, diagnostic evaluation, and treatment for adrenal metastases, with emphasis on decision-making in oligometastatic and oligoprogressive disease. The review was developed using Scale for the Assessment of Narrative Review Articles principles, with focused literature retrieval from biomedical databases, guideline sources, landmark series, systematic reviews, comparative studies, and reports on imaging, biopsy, adrenalectomy, percutaneous ablation, and stereotactic body radiotherapy. Cross-sectional imaging remains central, but indeterminate lesions often require multiparametric assessment using adrenal-protocol computed tomography (CT), magnetic resonance imaging, and selected positron emission tomography/CT. Biopsy should be reserved for cases in which imaging remains equivocal and histology will change management. For carefully selected patients with isolated or limited adrenal metastasis, adrenalectomy may provide durable local control and survival. Percutaneous ablation and stereotactic body radiotherapy offer lower-morbidity alternatives for non-operative candidates or anatomically challenging lesions. Management should follow an intent-based framework integrating diagnostic confidence, tumor biology, systemic treatment response, lesion anatomy, patient fitness, and goals of care.

Key Words: Adrenal gland; Adrenalectomy; Metastases; Percutaneous ablation; Stereotactic body radiotherapy

Core Tip: Adrenal metastasis is increasingly identified during staging and surveillance, but outcomes vary widely by primary tumor biology, rate of progression, and whether disease is truly isolated. Management should follow an intent-based pathway: Confirm diagnosis with high-quality imaging, reserve biopsy for indeterminate lesions when results will change treatment and select local therapy accordingly. For carefully chosen patients, adrenalectomy offers durable control; percutaneous ablation and stereotactic body radiotherapy provide effective, lower-morbidity alternatives for non-operative candidates or anatomically challenging lesions. Standardized selection criteria and stratified reporting are essential to define when local treatment meaningfully changes trajectory.

INTRODUCTION

Adrenal metastases are clinically important because the adrenal gland is a common site of secondary spread in advanced malignancy, although reported prevalence varies substantially by primary tumor type, stage, and ascertainment method. The adrenal gland is the 4th most common site of metastasis in cancers and metastatic tumor is the most common malignant lesion involving the adrenal gland and 2nd most common type of tumor found in the adrenal gland after benign adenomas[1]. Although metastases are not uncommon, they account for only 2% of adrenal incidentalomas. Autopsy series demonstrate metastases to the adrenals in 3% of subjects[2] whereas in patients with known malignancies, adrenal lesions are metastatic in up to 75% of cases[3]. Isolated unilateral adrenal metastasis is less common compared to bilateral metastases but, if unilateral, they occur more commonly on the left side[4]. Autopsy series, incidentaloma cohorts, and oncologic imaging cohorts should not be interpreted interchangeably. In patients with a known extra-adrenal malignancy, the key clinical issue is not simply prevalence, but whether an adrenal lesion is benign, metastatic, isolated, or part of more widespread progression[5]. It is very rare for adrenal metastasis to occur without the discovery of a detectable primary tumor. Despite increasing detection, the main challenge is no longer recognizing adrenal metastasis, but deciding when an adrenal lesion warrants further characterization, biopsy, or local treatment, and which local modality is most appropriate in a given disease state. This review aims to provide an updated synthesis of the epidemiology, diagnostic evaluation, and treatment options for adrenal metastases.

METHODOLOGY OF THE REVIEW

This manuscript was prepared as a narrative review. During manuscript development, the domains of the Scale for the Assessment of Narrative Review Articles were considered as a framework to improve transparency, structure, and reporting quality[6]. PubMed/MEDLINE, Scopus and Google Scholar were searched from database inception to 10 April 2026, with targeted review of relevant guideline documents and citation chaining from key articles. Search terms included combinations of “adrenal metastasis”, “adrenal metastases”, “adrenalectomy”, “adrenal ablation”, “radiofrequency ablation”, “microwave ablation”, “cryoablation”, “irreversible electroporation”, “stereotactic body radiotherapy”, “SBRT”, “oligometastatic”, and “oligoprogressive”. A focused PubMed search using adult, human, English-language, clinical study, multicenter study, observational study, clinical trial and meta-analysis filters identified 188 records. Titles and abstracts were screened for relevance to adrenal metastasis epidemiology, diagnostic evaluation, biopsy, surgery, percutaneous ablation, radiotherapy, systemic therapy context and guideline-based decision-making. Exclusion criteria included pediatric studies, animal-only studies, non-English articles, pituitary or bone metastasis-focused studies, pheochromocytoma-specific articles without relevance to metastatic adrenal disease, isolated case reports without broader management relevance, and articles not addressing adrenal metastasis diagnosis or treatment. Fifty-nine sources were included after relevance screening, citation chaining, and guideline review. Because of heterogeneity in study design, primary tumor type, disease burden, systemic therapy context, local modality and reported outcomes, evidence was synthesized narratively rather than quantitatively. This review was not registered as a systematic review and no formal risk-of-bias assessment or meta-analysis was performed.

ANATOMICAL-BIOLOGICAL BASIS AND PATTERNS OF SPREAD

The adrenal glands possess a rich sinusoidal blood supply that predisposes them to hematogenous metastasis. Tumor seeding may occur early and remain clinically silent leading to incidental detection of adrenal metastases during cancer staging. Although the adrenal gland is normally closely apposed to the superior pole of the kidney, pathological enlargement, particularly from metastatic involvement changes its operative ‘neighbourhood’, bringing the right adrenal gland into a closer relationship with the liver and the left adrenal into a closer relationship with the pancreas. Cross-sectional imaging is the mainstay of diagnosis with differentiation between benign adrenal lesions and metastases still remaining poorly defined. Lung cancer is one of the commonest primary sources of adrenal metastasis, but reported frequencies vary widely by stage and study design; these figures should therefore be interpreted as context-specific rather than universal[7]. Other cancers that often metastasize to the adrenal glands are breast, pancreatic, renal, esophageal, liver, melanoma and gastrointestinal tract cancers[1]. These metastases are often asymptomatic. Symptomatic cases, albeit rare may present with adrenal insufficiency or haemorrhage. In a 30-year retrospective teaching-hospital series of 464 patients with histologically confirmed adrenal metastases, Lam and Lo[2] reported that only 4.3% (n = 20) were clinically symptomatic-most commonly presenting as an adrenal mass, adrenal insufficiency (5 cases) or, rarely, massive haemorrhage-reinforcing that metastatic adrenal involvement is usually clinically silent. Some reports have suggested that adrenal metastasis from gastrointestinal and hepatobiliary malignancies often present in advanced stages thereby resulting in diagnostic and therapeutic dilemmas. A continuous improvement in imaging technology over the past few decades has led to an increase in the detection of such lesions with some reports suggesting the use of fine needle cytology for diagnosis given that only 45% of such cases are correctly diagnosed clinically[8].

DIAGNOSTIC EVALUATION

In patients with known malignancy, adrenal evaluation is not merely a radiologic exercise in lesion classification. The clinically decisive question is whether the lesion represents a benign incidentaloma, a non-actionable component of widespread progression, or a potentially trajectory-changing site of limited metastatic disease.

Computed tomography (CT) scan has been conventionally used for diagnosis. It relies on size and multiphasic assessment, density and contrast dynamics. It has a low sensitivity and on routine CT or magnetic resonance imaging (MRI), the diagnostic features of adrenal metastases can be nonspecific. Metastases tend to be heterogeneous with irregular margins, particularly when large. However, small metastatic lesions may be homogeneous with smooth margins, thus mimicking benign lesions. Therefore, further evaluation is often needed, especially in cancer patients with no other sites of metastases, given the impact on management and survival outcomes. Metastases typically have attenuation values of higher than 10 HU on unenhanced CT. They usually do not demonstrate significant post-enhancement washout on delayed phase, with an absolute washout of less than 60% and relative washout of less than 40%. An example of such an adrenal nodule seen on triphasic CT being suspicious for metastasis is seen in Figure 1.

Figure 1 A 70-year-old male with 18cm pT1bN0M0 hepatocellular carcinoma post laparoscopic left lateral sectionectomy underwent Yttrium-90 radioembolisation for recurrence (blue arrow) at 12 months. A triphasic computerised tomography 2 months after Yttrium-90 (about 14 months after hepatectomy) demonstrated a new right adrenal nodule (yellow arrow) suspicious for metastasis and is being treated with systemic therapy.

A markedly hyperattenuating non-haemorrhagic, non-calcified adrenal lesion on unenhanced CT should raise suspicion for metastasis, but attenuation should be interpreted together with morphology, washout behaviour, and the oncologic context rather than in isolation. In a systematic review of nine observational retrospective university-hospital studies (median 125 patients, range: 20-356) evaluating CT texture analysis/radiomics in adrenal lesions, Crimì et al[9]. reported a pooled median AUC of 0.86 for discriminating benign vs malignant masses, supporting texture analysis as a promising adjunct when conventional imaging criteria are indeterminate. One limitation of standard CT imaging is that it is typically performed in a single phase, which precludes washout calculation, and abdominal images are often acquired with 3 mm slice thickness.

On MRI, metastases usually exhibit low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with heterogeneous enhancement after administration of contrast material. T2-weighted MRI has been shown to have a high accuracy rate in diagnosing adrenal metastasis[10,11]. Metastases typically do not demonstrate signal drop on opposing-phase compared to in-phase pulse sequences, with the exception of metastases containing intracytoplasmic lipid.

MRI is particularly helpful when CT findings are indeterminate, especially in lipid-poor lesions. Chemical-shift imaging is useful because adenomas typically demonstrate signal loss on opposed-phase imaging, whereas metastases usually do not, although overlap can occur in lipid-containing metastases[10]. Diffusion-weighted imaging and other quantitative MRI techniques remain adjunctive rather than standalone discriminators. In a comparative imaging review of adrenal tumors, Ilias et al[10] highlight that because T2 signal overlap limits discrimination, chemical-shift MRI (in-phase vs opposed-phase) can help differentiate adenomas from metastases, with an adreno-splenic ratio < 70% supporting adenoma (78% sensitivity; 100% specificity).

Advanced CT methods, including texture analysis/radiomics and photon-counting CT-derived parameters, may provide adjunctive discrimination when conventional CT criteria are indeterminate. However, these methods should be interpreted as workflow-supporting tools rather than replacements for dedicated adrenal CT/MRI protocols or multidisciplinary review[9,12].

Fluorodeoxyglucose positron emission tomography (PET)/CT may improve characterization of indeterminate adrenal lesions in oncologic patients, especially when interpreted together with unenhanced CT attenuation and the broader metastatic pattern. However, diagnostic thresholds vary across studies, and PET/CT is best viewed as a problem-solving and staging adjunct rather than a standalone discriminator[13]. These newer imaging modalities have provided close sensitivity, specificity, and accuracy levels and are refining diagnostic confidence in routine clinical workflows[14,15].

In practice, evaluation should follow a stepwise workflow. Dedicated CT or MRI should first determine whether the lesion can be confidently characterized as benign using attenuation, washout, or chemical-shift features. If imaging remains indeterminate in a patient with known malignancy, PET/CT may improve staging confidence and clarify whether the adrenal lesion is isolated or part of disseminated disease. Biopsy or fine needle aspiration cytology should be reserved for cases in which imaging remains equivocal and histology would alter management, particularly when local therapy is being considered for a potentially solitary metastasis or when tissue is needed for treatment planning. At every stage, biochemical exclusion of pheochromocytoma is essential before invasive sampling. Thus, tissue diagnosis should be viewed as a selective management-enabling intervention rather than a routine confirmatory test. Adrenal metastases are usually detected incidentally, with about 96% being asymptomatic[7].

TREATMENT

The treatment options for adrenal metastases include surgery, percutaneous ablation, conventional radiation therapy and stereotactic body radiation therapy (SBRT)[16].

Patient selection principles and intent

For clinical decision-making, adrenal metastases should be stratified into four practical states: (1) Truly isolated adrenal metastasis, where eradication of all visible disease may be feasible; (2) Oligometastatic disease with limited, otherwise controllable extra-adrenal disease; (3) Oligoprogressive disease, where the adrenal lesion progresses despite otherwise effective systemic therapy; and (4) Polymetastatic disease, where local treatment is mainly palliative or symptom-directed. This state-based framework is useful because the rationale for surgery, ablation, or SBRT differs across these scenarios. In the first two settings, local therapy may serve metastasis-directed consolidation; in oligoprogression, it may preserve an otherwise effective systemic regimen; and in polymetastatic disease, treatment is usually selected for symptom relief, local control, or prevention of future complications rather than trajectory-changing intent.

Adrenalectomy for adrenal metastasis has been well described, but indications and the magnitude of oncologic benefit remain incompletely defined across primary tumor types. Early reports focused on resection of apparently isolated metastases[17,18], whereas more contemporary series include selected patients with otherwise stable extra-adrenal disease[19]. The most consistent signal across retrospective studies is that carefully selected patients can achieve durable local control and prolonged survival, particularly when disease burden is limited, systemic disease is controlled, and complete local treatment is feasible[20]. However, these outcomes are strongly confounded by selection, and surgery should not be interpreted as uniformly superior to non-operative management across all tumor contexts. Key contemporary adrenalectomy series are summarized in Table 1[21-26]. Collectively, these data support metastasectomy in carefully selected patients, while underscoring the heterogeneity in outcomes by primary tumor biology and disease context. Importantly, these data should not be interpreted as proof that adrenalectomy is inherently superior to non-surgical local therapy. Patients selected for surgery are often fitter, have lower disease burden, more favourable tumor biology, and better-controlled systemic disease. Adrenalectomy should therefore be framed as the most definitive local option for carefully selected surgically fit patients, rather than as the default treatment for all patients with adrenal metastasis[21-26].

Table 1 Adrenalectomy and comparative local therapy studies for adrenal metastases.

Ref.	Design/setting	n (patients)	Most common primaries (number)	Approach	Key outcomes	Evidence strength
Muth et al[21]	Institutional series (1996-2007), ADX for metastasis	30	Renal cell carcinoma (9), melanoma (5), NSCLC (5), colorectal carcinoma (4), others	10 laparoscopic, 20 open	Median survival 23 months; local recurrence: Laparoscopic 1/10, open 1/20; no surgical complications	Retrospective institutional series; heterogeneous primaries; selection bias
Drake et al[22]	Retrospective cohort with comprehensive follow-up (1995-2016)	62	NSCLC (20), renal cell carcinoma (14), melanoma (8)	59/62 laparoscopic	5-year survival 37%; median survival 34 months (NSCLC 26; renal cell carcinoma 67; melanoma 30); 0 deaths ≤ 30 days, 6 complications, 2 conversions	Retrospective cohort with SEER comparison; selection bias
Vazquez et al[23]	Mayo cohort vs SEER stage-matched controls (1992–2010)	166	Kidney (60), lung (24), sarcoma (19), colon (15), pancreas (13), others	29 Laparoscopic, 46 open, 91 combined	Better OS in ADX cohort vs SEER controls at 1-3 years for sarcoma/kidney/Lung/pancreas primary tumors	Retrospective comparative cohort vs historical controls
Hwang et al[24]	2-center retrospective cohort (2004-2012)	32	Lung (11), liver (5), colon (4), kidney (4), stomach (3), pancreas (2), others	12 Laparoscopic, 20 open	No surgical complications. Recurrence rate 625%	Small retrospective two-center pilot cohort
Lütscher et al[25]	Single-center retrospective: SBRT vs ADX	41	NSCLC (26), renal cell carcinoma (4), adenocarcinoma of the gastrointestinal tract (4), small-cell lung cancer (2), others	ADX (14) vs SBRT (27)	Local control (1-year/2-year): 100%/100% surgery vs 70.0%/52.5% SBRT (P = 0.001); progression free survival (1-year/2-year): 40.2%/32.1% surgery vs 10.6%/10.6% SBRT (P = 0.223); OS (1-year/2-year): 83.3%/83.3% surgery vs 67.0%/40.2% SBRT (P = 0.031)	Selection bias acknowledged. SBRT showed less ≥ grade 2 toxicity incidence (6.5%) compared to surgery (23.5%)
Liu et al[26]	Retrospective comparative (2008-2018): RFA vs ADX	60	Hepatocellular carcinoma (31), NSCLC (8), renal cell carcinoma (8)	RFA (29) vs ADX (31)	Local tumour progression (1-year/2-year/3-year): 17.1%/30.9%/44.7% RFA vs 6.5%/6.5%/6.5% ADX (P = 0.028); OS (1-year/2-year/3-year): 85.0%/42.4%/27.8% RDA vs 93.0%/66.1%/52.3% ADX (P = 0.057)	Retrospective RFA vs adrenalectomy comparison; selection bias

ADX: Adrenalectomy; NSCLC: Non-small-cell lung cancer; OS: Overall survival; RFA: Radiofrequency ablation; SBRT: Stereotactic body radiotherapy; SEER: Surveillance, epidemiology, and end results.

Adrenal metastasectomy may be considered in carefully selected patients, particularly when the adrenal lesion is isolated or part of limited metastatic disease, systemic disease is controlled, and complete local treatment appears feasible. However, high level prospective data to support surgery in oligoprogressive disease remains limited compared to isolated and oligometastatic adrenal metastasis. Hence patient selection for metastasectomy should be individualized within a multidisciplinary framework, because outcomes vary substantially by primary tumor biology, disease presentation, and extra-adrenal metastatic burden. A dedicated adrenal multidisciplinary team meeting should comprise of endocrinologists, radiologists, pathologists, case managers, and surgeons with interest in adrenal pathology.

For operative planning, pathological enlargement can alter the practical neighbourhood of the gland. On the right, bulky adrenal lesions may about the liver, duodenum, and inferior vena cava, making exposure and early venous control technically demanding. On the left, large adrenal lesions may lie close to the pancreatic tail and splenic vessels, increasing the risk of difficult dissection, bleeding, and pancreatic injury. This anatomical relationship between the left adrenal gland and the adjacent vessels and spleen is shown in Figure 2.

Figure 2 A 66-year-old man underwent open extended right hemihepatectomy for pT3Nx hepatocellular carcinoma. At 11 months postoperatively, surveillance computerised tomography scan demonstrated an enlarging left adrenal mass (yellow arrow) suspicious for metastasis. Left adrenalectomy with splenectomy was done and he remains alive at 72 months.

Percutaneous ablation offers a minimally invasive local treatment option for selected adrenal metastases, particularly small lesions in non-operative candidates. Percutaneous ablation includes radiofrequency ablation, microwave ablation, cryoablation and, less commonly, irreversible electroporation. Radiofrequency ablation and microwave ablation rely on thermal injury, with microwave ablation potentially achieving larger and faster ablation zones. Cryoablation allows visualization of the ice ball and may be useful near selected critical structures, while irreversible electroporation is non-thermal and may be considered when thermal injury to adjacent structures is a concern[27-32]. Across techniques, careful attention is required to lesion size, proximity to kidney, bowel, pancreas, spleen, inferior vena cava and diaphragm, and the risk of hypertensive episodes even in non-pheochromocytoma lesions. Reported outcomes of percutaneous adrenal ablation are summarized in Table 2, including technical success, local progression, survival, and procedure-specific safety signals.

Table 2 Percutaneous ablation for adrenal metastases.

Ref.	Modality	n (patients/lesions)	Technical success	Local control/progression	Survival	Complications
Hasegawa et al[29]	Radiofrequency ablation (± arterial embolization)	35/41	Enhancement disappeared after initial radiofrequency ablation in 83% (29/35) and 94% (33/35) after 2nd radiofrequency ablation	Local tumor progression 23% (8/35); overall tumor control 77% at last follow-up	Overall survival 1-year/3-ear/5-year: 75%/34%/30%; median overall survival 26.0 months	Major complication 8.3% (4/48 sessions); no mortality
Aoun et al[30]	Cryoablation	34/40	Not reported	Local recurrence 10% overall; 0% if ≤ 3 cm vs 21% if >3 cm	NR	Major complication ≥ grade 3: 5% (2/40); blood pressure escalation associated with residual adrenal tissue
Zhang et al[31]	Cryoablation vs microwave ablation (non-small-cell lung cancer isolated adrenal metastasis)	68/68	Primary complete ablation: 91.4% (cryoablation) vs 93.9% (microwave ablation); secondary complete ablation 100% both	Local progression: 22.9% (cryoablation) vs 24.2% (microwave ablation)	Median overall survival: 25 months (cryoablation) vs 29 months (microwave ablation)	Hypertensive crisis: 11.4% (cryoablation) vs 9.1% (microwave ablation)
Narayanan et al[32]	Irreversible electroporation	6/7	Technical success 100%	Local progression 2/7; median local progression free survival 10.9 months	Median overall survival 8.3 months	Only one grade 1 complication; distant progression 4/6

Radiotherapy has been mainly described for palliative symptom relief with only a partial response in most described reports[33,34]. Conventional radiotherapy has historically been used mainly for palliation of symptomatic adrenal metastases. In contrast, SBRT has emerged as a metastasis-directed option for selected oligometastatic or oligoprogressive patients, offering high local control with low rates of severe toxicity in contemporary series[35]. Effective delivery depends on careful patient selection, motion assessment, reproducible immobilization, and 4D CT-based planning. Key SBRT/radiotherapy series for adrenal metastases-including dose/fractionation, local control, and toxicity-are summarized in Table 3[36-45]. Reported adrenal stereotactic body radiotherapy schedules vary across studies, commonly using hypofractionated regimens in the range of approximately 30-55 Gy delivered in 3-9 fractions, with biological effective dose, lesion volume, respiratory motion management, and organ-at-risk constraints influencing local control and toxicity[36-45].

Table 3 Stereotactic body radiation therapy and radiation therapy series for adrenal metastases.

Ref.	Study design/population	n (patients/lesions)	Dose/fractions	Key outcomes	Toxicity
Chen et al[36]	Systematic review + pooled meta-analysis (photon SBRT)	39 studies; 1006 patients	Median follow-up 12 months; median BED10 67 gray	Pooled overall response 54.6%; pooled LC 1-year 82%, 2-year 63%; pooled OS 1-year 66%, 2-year 42%; dose-LC association	Grade ≥ 3 toxicity 1.8%
Yuste et al[37]	Multi-institution (11 French centers), retrospective; oligometastatic SBRT	110/121	Median prescription 40 gray; mean BED10 74.2 gray; median planning target volume 70 cm3	LC 1-year 85.9%, 2-year 72.5%; median OS 31.6 months, median PFS 8.5 months	No grade 3-4 toxicity; LC improved with peri-SBRT systemic treatment and BED10 ≥ 50 gray
Franzese et al[38]	Multicenter (3 Italian centers), retrospective; oligorecurrent/oligoprogressive	142/149	Median SBRT dose 40 gray (10-60); median lesion volume 28.5 cm3; follow-up 14.4 months	OS 1-year 72.3%, 2-year 53.5%; LC 1-year 85.4%, 2-year 79.2%; PFS 1-year 37.7%, 2-year 24.8%	Grade 1 14.7%, grade 2 2.1%; BED10 and lung primary associated with LC
Franzese et al[39]	Prospective phase II trial; endocrine function focus	36/(treated lesions not specified)	45 gray/3 consecutive fractions; median follow-up 9.5 months	LC 1-year 94.7%, 2-year 88.4%; PFS median 14.7 months (1-year 50.5%, 2-year 29.8%); OS 1-year 62.9%, 2-year 44.1%	No grade ≥3 toxicity; mild side effects 22.2%; endocrine/electrolytes largely preserved
Holy et al[40]	Single-institution; non-small-cell lung carcinoma adrenal metastasis (isolated vs multi-metastasis)	18/(lesions not specified)	5 × 4 gray to 5 × 8 gray (varied intent/size); median max dose 132% (center)	Median PFS: 4.2 months (all) vs 12 months (isolated 13/18); LC 77% (10/13) for isolated group; median OS: 21 months (all) vs 23 months (isolated 13/18)	Grade 1 nausea 6/18; Multiple gastric ulcers at 2 weeks 1/18; Gastric and duodenal ulcers at 4 weeks 1/18
Zhao et al[41]	Two-institution retrospective; lung cancer adrenal metastasis	30/32	Median 44.4 gray (35-50) in median 5 fractions (3-8); corresponding BED10 85.5 gray	Response: Complete response 23.3%, partial response 33.3%, stable disease 33.3%, progressive disease 16.7%; LC 6-month/1-year/2-year 96.9%/96.9%/72.7%; OS 6-month/1-year/2-year 85.6%/58.1%/54.0%; PFS 6-month/1-year/2-year 39.5%/24.6%/8.2%	1 grade 3 diarrhea; pain improvement reported; BED10 ≥ 85.5 gray + gross tumor volume < 30 mL correlated with LC (univariate)
Torok et al[42]	Single-institution retrospective; mixed primaries	7/9	Single fraction median 16 gray (10-22) to 80% isodose; or 3 fractions median 27 gray (24-36)	Imaging response (8 Lesions): 1 complete response, 2 partial response, 5 stable; 1-year LC 63%; median time to local failure 12 months; median OS 8 months from SBRT	No acute or late toxicity. Concluded SBRT safely deliverable (single or hypofractionated)
Scouarnec et al[43]	Single-institution retrospective; multiple primaries	31/33	30-55 gray in 3-9 fractions; median BED10 112.5 gray	Competing-risk LC 1-year 96.5%, 2-year 92.6%; median OS 33.5 months; median PFS 7.4 months; responses: Complete response 32.3%, partial response 32.3%, stable disease 25.8%	Grade 1-2 toxicity 42.4%; no acute ≥ 3 or late toxicity
Plichta et al[44]	Single-institution retrospective; oligometastatic (≤ 5 sites)	10/(lesions not specified)	30-48 gray in 3-5 fractions; median follow-up 6 months	Median OS 9.9 months; median PFS 3.4 months; 1 Local progression at 18.8 months; 7 developed new distant metastasis	Acute: Nausea (grade 1-2) 4, fatigue (grade 1) 3, diarrhea (grade 1) 1; GI bleed at 3 months (noted as late event)
Buergy et al[45]	Retrospective; hypo-/conventional image-guided radiotherapy (includes SBRT intent language)	18/22	Median 35 gray (20-60) in median 7 fractions (4-25)	Median OS 11.9 months; 5 local failures (22.7%); OS differed by state: Oligometastatic 33 months, oligoprogressive 6.5 months, palliative/polymetastatic 1.6 months	No grade ≥ 3 toxicity; symptom improvement in all treated for symptomatic lesions

BED10: Biological equivalent dose calculated with an α/β ratio of 10; LC: Local control; OS: Overall survival; PFS: Progression-free survival; SBRT: Stereotactic body radiotherapy; GI: Gastrointestinal.

Modality-specific toxicity

The toxicity profile differs across locoregional modalities. Adrenalectomy carries perioperative risks of bleeding, pancreatic or splenic injury for left-sided lesions, and vascular risk related to the short right adrenal vein and inferior vena cava interface[21-26]. Percutaneous ablation may be associated with pain, bleeding, thermal injury to adjacent structures, hypertensive episodes, adrenal insufficiency, and local progression when lesions are large[29-32]. Stereotactic body radiotherapy is non-invasive and generally well tolerated, but acute nausea, fatigue, abdominal pain, gastritis or enteritis, gastrointestinal ulceration or bleeding, renal dose exposure, and adrenal insufficiency should be considered, especially for bilateral lesions[36-45].

The choice of local adrenal treatment should be interpreted within the systemic therapy context. In isolated or oligometastatic disease, local therapy may be used as consolidation after favourable systemic response or when all visible disease appears amenable to definitive control. In oligoprogressive disease, local treatment of the adrenal lesion may allow continuation of an otherwise effective systemic regimen, thereby delaying treatment switch. Conversely, in rapidly progressive or polymetastatic disease, local therapy is less likely to alter overall trajectory and is more appropriately selected for symptom control, or prevention of local complications.

Experience with metastasis-directed therapy in other oligometastatic settings has supported interest in local treatment for adrenal metastases. Outcomes depend on primary tumor biology, metastatic pattern, and systemic therapy responsiveness. Benefit after adrenalectomy is not uniform across cancer types, making tumor biology a key selection factor. In a large multi-institutional series, the most common primary tumors were lung, renal cell, melanoma, sarcoma, and colorectal, with improved survival in selected patients[46]. The high prevalence of lung primaries in most reported series of adrenalectomy for adrenal metastasis in light of the striking difference in OS and progression free survival between lung and non-lung primaries is noteworthy and warrants further investigation[47,48]. In sarcoma, melanoma, and colorectal cancer, the converse pattern was observed, with relatively brief disease-free period after adrenalectomy, but longer survival. More than two-thirds of patients were alive 5 years after surgery. This may be reflective of highly effective systemic treatments in these cancers. In the absence of a randomized clinical trial it would be challenging to prove a survival advantage to adrenalectomy in this clinical context. These observations support consideration of adrenalectomy in highly selected patients, but the retrospective nature of the data and the likelihood of selection bias limit firm conclusions about causal survival benefit.

No differences in oncological outcomes or margin status between laparoscopic and open surgery have been noted in most studies[49,50]. The data recommending laparoscopic vs a retroperitoneoscopic approach are heterogenous. While open adrenalectomy is generally reserved for very large or locally invasive adrenal lesions, minimally invasive adrenalectomy is typically associated with less postoperative pain, shorter length of stay, and faster recovery, with comparable longer-term outcomes in appropriately selected cases[51]. Current evidence suggests broadly similar perioperative outcomes between laparoscopic transabdominal and retroperitoneal approaches in terms conversion rate, blood loss, operative duration, time to ambulation, and resumption of oral intake. Approach choice should therefore be individualized to tumor size, body habitus, prior surgery, and surgeon expertise[52]. The retroperitoneal approach offers direct access to the adrenal while avoiding bowel handling potentially reducing ileus risk and can facilitate bilateral procedures in a single position. However, it is less suitable for large tumors or obesity and has a significant learning curve. The lateral transperitoneal approach provides generous working space and visualization often leveraging gravity for retraction and is commonly preferred for larger tumors or obese patients but can be more challenging after prior major intra-abdominal operations[53]. Further, retroperitoneoscopic approach has an advantage of undisturbed tissue planes in patients who have had prior abdominal surgery, while the transperitoneal approach allows for combined resections with other abdominal operations in the same setting. Technical efficiency in adrenal metastasectomy often hinges on early adrenal vein identification and control on the right by defining the inferior vena cava plane to the short adrenal vein, and on the left by medial dissection along the renal vein to the adrenal vein-before completing gland mobilization.

The practical question is which modality is best aligned with disease state, anatomical feasibility, clinical presentation, and systemic-treatment. Adrenalectomy remains the most definitive local option when disease is isolated, complete resection is feasible, and the patient is fit for surgery. Percutaneous ablation is attractive for smaller lesions and patients at high risk for surgery. SBRT is especially useful for oligometastatic or oligoprogressive settings, for anatomically challenging lesions, or when a non-invasive outpatient strategy is desired. All modalities are complementary and not competing. Figure 3 provides a framework for management approach for adrenal metastatic lesions.

Figure 3 A framework for management approach for adrenal metastatic lesions. CT: Computed tomography; MRI: Magnetic resonance imaging; FDG: Fluorodeoxyglucose; PET: Positron emission tomography; FNAC: Fine needle aspiration cytology; SBRT: Stereotactic body radiotherapy; RFA: Radiofrequency ablation; MWA: Microwave ablation; MDT: Multidisciplinary team.

Recent guideline-level recommendations provide guidance for work-up and patient selection. Current guidance is strongest in supporting multidisciplinary selection, high-confidence lesion characterization, and selective biopsy only when histology will alter management. The American Association of Endocrine Surgeons adrenalectomy guideline[54] suggests that resection may be offered to highly selected patients with adrenal metastases, whereas the 2023 European Society of Endocrinology/European Network for the Study of Adrenal Tumors guideline[55] advises that, in patients with extra-adrenal malignancy, surgery should be considered when a unilateral adrenal mass may represent the only metastasis and resection is oncologically reasonable; biopsy should be reserved for indeterminate lesions only when histology would change management. In RCC-specific guidance, the European Association of Urology[56] supports metastasis-directed therapy, including metastasectomy or ablation, when complete local treatment is feasible in favourable disease, whereas the European Society for Medical Oncology[57] cautions that metastasectomy is not routinely recommended within 1 year of nephrectomy. These recommendations support careful selection. Table 4 summarizes the key guidelines and their practical implications[54-58].

Table 4 Summary of guideline recommendations and practical implications.

Guideline/source	Scope/context	Directness to adrenal metastases	Relevant message
AAES adrenalectomy guideline (2022)[54]	General adrenal surgery	Direct	Multidisciplinary team selection; biopsy rarely; resection may be offered to highly selected patients
ESE/ENSAT adrenal incidentaloma guideline (2023)[55]	Adrenal mass evaluation in patients with extra-adrenal malignancy	Direct for work-up	Metanephrines; positron emission tomography/computerised tomography/surgery/biopsy if management changes; consider surgery if only metastasis
EAU RCC guideline (2024/2025)[56]	Metastatic renal cell carcinoma	Direct for renal cell carcinoma	Consider metastasectomy/ablative therapy in favourable disease if complete resection is feasible
ESMO RCC guideline (2024)[57]	Metastatic renal cell carcinoma	Direct for renal cell carcinoma	Metastasectomy not routine within 1 year of nephrectomy; local therapy in selected cases
SAGES adrenal pathology guideline (2013)[51]	Operative approach to adrenalectomy	Indirect	Minimally invasive adrenalectomy preferred for suitable non-primary adrenal cancer pathology
NCCN Guidelines for Patients: Kidney Cancer (2025)[58]	Patient-facing kidney cancer guidance	Indirect; renal cell carcinoma specific	Oligometastatic options include metastasectomy, radiation, or ablation

AAES: American Association of Endocrine Surgeons; ESE/ENSAT: European Society of Endocrinology/European Network for the Study of Adrenal Tumors; ESMO: European Society for Medical Oncology; EAU: European Association of Urology; SAGES: Society of American Gastrointestinal and Endoscopic Surgeons; NCCN: National Comprehensive Cancer Network.

These recommendations provide useful guardrails for work-up and selection, but they do not create a universal hierarchy between adrenalectomy, percutaneous ablation, stereotactic body radiotherapy, systemic therapy, and palliation across all primary tumor types[54-58]. Therefore, treatment selection should remain individualized according to disease state, primary tumor biology, systemic-treatment response, lesion size and location, patient fitness, and intended treatment goal. To translate this evidence into practical multidisciplinary decision-making, Table 5 compares the main treatment strategies for adrenal metastases according to candidate profile, advantages, limitations, toxicity considerations, and level of evidence.

Table 5 Practical comparison of treatment strategies for adrenal metastases.

Strategy	Ideal case	Advantages	Limitations	Safety considerations	Evidence
Adrenalectomy	Isolated adrenal metastasis or oligometastatic disease where complete local control is feasible; surgically fit patient	Definitive resection, tissue diagnosis, local control, potential durable survival in selected patients	Requires operative fitness; benefit is highly selection-sensitive; less suitable for uncontrolled polymetastatic disease	Bleeding, adjacent-organ injury, conversion, pancreatic/splenic injury on the left, inferior vena cava/right adrenal vein risk on the right	Mostly retrospective cohorts and comparative series; no adrenal-specific randomized trial[21-26]
Percutaneous ablation	Small adrenal lesions; non-operative candidates; patients needing lower-morbidity local treatment	Minimally invasive, repeatable, short hospital stay, useful when surgery is high-risk	Local control is size-sensitive; limited evidence for large/invasive lesions; proximity to bowel, pancreas, kidney, diaphragm, or major vessels may limit feasibility	Pain, bleeding, thermal injury, hypertensive crisis, adrenal insufficiency, incomplete ablation/local progression	Retrospective series; heterogeneous modalities and lesion-size thresholds[27-32]
Stereotactic body radiotherapy	Oligometastatic or oligoprogressive disease; non-surgical candidates; anatomically difficult lesions; outpatient local therapy	Non-invasive, high local control in selected series, can preserve systemic therapy continuity	Dose/fractionation varies; organ-at-risk constraints may limit dose; response assessment may be delayed	Nausea, fatigue, abdominal pain, gastritis/enteritis, ulceration/bleeding, renal dose exposure, adrenal insufficiency especially after bilateral treatment	Systematic review plus mostly retrospective cohorts; limited prospective data[36-45]
Conventional radiotherapy	Symptomatic disease, pain, bleeding risk, palliation when ablative treatment is not appropriate	Widely available; useful for symptom relief	Less ablative than stereotactic body radiotherapy; limited durable-control data	Gastrointestinal toxicity, fatigue, incomplete symptom response	Older and mostly palliative evidence[33,34]
Systemic therapy/best supportive care	Polymetastatic or rapidly progressive disease; adrenal lesion not dominant driver; poor local therapy candidate	Treats whole-body disease; aligns with primary tumor biology and goals of care	May not rapidly control symptomatic or threatening adrenal lesion	Regimen-specific toxicity; adrenal insufficiency if bilateral adrenal involvement progresses	Primary tumor-specific evidence; adrenal-specific comparative data limited[54-58]

Tumor-specific biology, systemic therapy and immune checkpoint inhibitors

The expected benefit of adrenal-directed local therapy is influenced by primary tumor biology and systemic therapy options. Lung cancer, renal cell carcinoma, melanoma, colorectal cancer, hepatocellular carcinoma and pancreaticobiliary malignancies differ in disease biology, response to systemic therapy, likelihood of oligometastatic control, and feasibility of salvage treatment after recurrence. Therefore, adrenal metastasis should not be managed as a single biological entity. In patients responding to systemic therapy, local treatment may be considered as consolidation when all visible disease is controllable. In oligoprogressive disease, local treatment of the adrenal lesion may allow continuation of an otherwise effective systemic regimen, including immune checkpoint inhibitor-based therapy[59]. In rapidly progressive polymetastatic disease, systemic therapy or best supportive care should remain the principal strategy, with local adrenal treatment reserved for palliation.

Timing of local treatment relative to systemic therapy

There is no universally accepted adrenal-specific interval between locoregional treatment and systemic therapy. Timing should be individualized according to treatment intent, systemic treatment class, patient fitness, wound-healing risk after surgery, and acute toxicity risk after ablation or radiotherapy. In isolated or oligometastatic disease, local therapy is often best considered after systemic disease stability or response has been demonstrated. In oligoprogressive disease, adrenal-directed therapy may delay systemic treatment switch, whereas in polymetastatic progression local treatment is usually reserved for symptom control or prevention of local complications[37,45,59].

As a narrative review, this article is intended to provide a clinically oriented synthesis rather than an exhaustive systematic review, and the conclusions should therefore be interpreted in the context of heterogeneous retrospective evidence and possible publication-selection bias. The literature on adrenal metastases has important limitations. Most comparative data are retrospective, involve small cohorts, combine heterogeneous primary tumor types, and apply inconsistent definitions of isolated, oligometastatic, and oligoprogressive disease. Reported endpoints also vary, with local control, progression-free survival, and overall survival often influenced by strong selection effects related to tumor biology, disease burden, and patient fitness. Thus, cross-modality comparisons should be interpreted cautiously.

CONCLUSION

Adrenal metastases are increasingly detected during staging and follow-up. Management remains heterogeneous because prognosis depends on primary tumor biology, metastatic burden, treatment response, and patient performance. In appropriately selected patients, surgery, percutaneous ablation, and SBRT can each provide local control. Survival differences between modalities should be interpreted cautiously because of selection bias.