Metastasis to the adrenal glands: An update

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.

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

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.

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.

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]