Guidelines Summary
European Society of Endocrinology
Clinical practice guidelines for the management of adrenocortical carcinoma (AC) in adults were released in 2018 by the European Society of Endocrinology. [53]
Diagnosis
Perform a detailed hormonal workup of all patients with suspected ACC to identify potential autonomous excess of glucocorticoids, sex hormones, mineralocorticoids, and adrenocortical steroid hormone precursors.
Perform a chest CT in addition to an abdominal-pelvic cross-sectional imaging (CT or MRI) in any case where there is high suspicion for AC.
Do not use adrenal biopsy in the diagnostic workup of patients with suspected AC unless there is evidence of metastatic disease that precludes surgery.
Surgery
Complete en bloc resection of all adrenal tumors suspected to be AC is recommended. Enucleation and partial adrenal resection is not recommended.
Open surgery for all tumors with radiological findings suspicious of malignancy and evidence for local invasion is recommended.
Routine loco-regional lymphadenectomy should be performed with adrenalectomy for highly suspected or proven AC. At a minimum, it should include the periadrenal and renal hilum nodes. All suspicious or enlarged lymph nodes identified on preoperative imaging or intraoperatively should be removed.
Perioperative hydrocortisone replacement in all patients with hypercortisolism who undergo surgery for AC is recommended.
Pathological work-up:
-
Use immunohistochemistry for steroidogenic factor 1 (SF1) for the distinction of primary adrenocortical tumors and non-adrenocortical tumors.
-
Use the Weiss system for the distinction of benign and malignant adrenocortical tumors.
-
Use Ki67 immunohistochemistry for every resection specimen of an adrenocortical tumor.
Adjuvant therapy:
-
Adjuvant therapy is not recommended for adrenal tumors with uncertain malignant potential.
-
Adjuvant mitotane treatment is recommended for those patients without macroscopic residual tumor after surgery who have a high risk of recurrence.
-
Administer adjuvant mitotane for at least 2 years, but not longer than 5 years, in patients without recurrence.
Treatment of recurrent and/or advanced AC:
-
For advanced AC not amenable to complete surgical resection, local therapeutic measures (eg, radiation therapy, radiofrequency ablation, chemoembolization) are of particular value .
-
Routine use of adrenal surgery in case of widespread metastatic disease at the time of first diagnosis is not recommended.
-
In patients with advanced AC at the time of diagnosis who do not qualify for local treatment, either mitotane monotherapy or mitotane plus EDP (etoposide, doxorubicin, cisplatin) is recommended.
-
Surgery is recommended for patients with recurrent disease that arises after a disease-free interval of at least 12 months.
Pregnancy and AC:
-
Prompt surgical resection is recommended when an adrenal mass suspected to be an AC is diagnosed in a pregnant patient.
-
Patients should avoid pregnancy while on mitotane treatment.
National Comprehensive Cancer Network
When an adrenal gland tumor is found on an imaging study, in patients with no history of prior or current malignancy and no risk, or suspicion, of adrenal metastasis, National Comprehensive Cancer Network (NCCN) recommendations for evaluation include an adrenal protocol: non-contrast CT (if Hounsfield units [HU] < 10, the tumor is probably benign and no further imaging is recommended; if > 10 HU, proceed with contrast CT with washout); or MRI with and without contrast.
The NCCN also recommends a biochemical workup for the following, in addition to the workup for AC [44] :
-
Hyperaldosteronism
-
Hypercortisolemia
-
Pheochromocytoma
-
Androgen excess
In patients with suspected AC, the NCCN recommends the following studies, to evaluate for metastases and local invasion:
-
Fluorodeoxyglucose (FDG) PET/CT
-
Chest CT with or without contrast
-
Abdominal/pelvic CT or MRI with contrast
-
Biochemical workup
Patients with resectable disease should undergo adrenalectomy, with the choice of open versus minimally invasive surgery based on tumor size, degree of concern regarding potential malignancy, and local surgical expertise. If AC is found, the patient should undergo genetic counseling and testing for inherited cancer syndromes, and consideration of microsatellite instability (MSI), mismatch repair (MMR), and tumor mutational burden (TMB) testing.
For localized AC, recommended treatment is resection of the tumor and adjacent lymph nodes, preferably by open adrenalectomy. If there is high risk for local recurrence (eg, positive margins, Ki-67 > 10%, rupture of capsule, large size, high grade), external-beam radiation therapy (EBRT) to the tumor bed should be considered. Adjuvant mitotane therapy may also be considered, although this is a category 3 recommendation (ie, there is major NCCN disagreement that the intervention is appropriate).
For patients with locoregional unresectable or metastatic disease, the NCCN recommends considering the following options:
-
Observation for clinically indolent disease with imaging and biomarkers (if functional) every 12 weeks
-
Resection of primary tumor and metastases if > 90% removable, particularly if functional
-
Local therapy (ie, stereotactic body radiation therapy [SBRT], thermal ablative therapies, liver-directed therapy)
-
Systemic therapy, preferably in a clinical trial
For systemic therapy, preferred regimens are cisplatin or carboplatin plus etoposide ± doxorubicin ± mitotane. Other recommended regimens are pembrolizumab ± mitotane or mitotane monotherapy; streptozocin ± mitotane is useful in certain circumstances.
-
A 68-year-old woman with a large right upper quadrant primary adrenocortical carcinoma with curvilinear calcification. Low-attenuation regions anteriorly are consistent with necrosis.
Tables
| Stage | T | N | M |
|---|---|---|---|
| I | T1 | N0 | M0 |
| II | T2 | N0 | MO |
| III | T1-2 |
N1 |
M0 |
T3 |
N0 | M0 | |
| IV | T3 |
N1 |
M0 |
T4 |
Any N |
M0 |
|
Any T |
Any N |
M1 |
