Adrenal Cortical Carcinoma

Adrenal Cortical Carcinoma (ACC) – Treatment Options

Introduction
Adrenal cortical carcinoma (ACC) is a rare and aggressive malignancy arising from the adrenal cortex. It may present as a functional tumor (producing cortisol, androgens, estrogens, or aldosterone) or as a non-functional mass detected incidentally. Symptoms vary based on hormonal excess (Cushing’s syndrome, virilization, feminization, hyperaldosteronism) and tumor burden (abdominal pain, mass effect, weight loss). Prognosis is generally poor, with high recurrence rates even after surgery. Treatment strategies focus on complete surgical resection, adrenolytic therapy, and systemic treatments for advanced disease.

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1. Surgical Management (Primary Curative Approach)

• Radical adrenalectomy (gold standard):

  • En bloc removal of adrenal gland with surrounding tissue.

  • Open surgery preferred over laparoscopy for large or invasive tumors.

• Resection of adjacent organs: Kidney, liver, or vena cava may be partially resected if invaded.

• Goal: Complete resection with negative margins (R0 resection).

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2. Medical Therapy

• Mitotane (adrenolytic agent):

  • Standard adjuvant therapy after resection and first-line in advanced disease.

  • Reduces risk of recurrence and controls hormone excess.

  • Requires serum level monitoring; adverse effects include GI toxicity, neurologic symptoms, and adrenal insufficiency.

• Glucocorticoid/mineralocorticoid replacement:

  • Often required due to mitotane-induced adrenal suppression or post-surgical adrenalectomy.

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3. Systemic Therapy for Advanced/Metastatic Disease

• Chemotherapy:

  • Combination regimens such as etoposide + doxorubicin + cisplatin (EDP) + mitotane (EDP-M) are standard.

  • Alternative regimens (streptozocin, gemcitabine-based) for refractory cases.

• Targeted and immunotherapy (investigational):

  • Tyrosine kinase inhibitors and immune checkpoint inhibitors are under study, but benefits remain limited.

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4. Radiotherapy

• Limited role in ACC:

  • Not effective for primary disease control.

  • Used in palliation (bone or brain metastases, local recurrence).

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5. Hormonal Symptom Control

• Cortisol excess (Cushing’s syndrome):

  • Ketoconazole, metyrapone, mitotane, or mifepristone.

• Androgen/estrogen excess:

  • Antiandrogens (flutamide, spironolactone) or aromatase inhibitors as supportive therapy.

• Mineralocorticoid excess:

  • Spironolactone or eplerenone for hyperaldosteronism.

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6. Monitoring and Long-Term Care

• Imaging (CT/MRI/PET): Every 3–6 months for first 2 years, then annually to detect recurrence.

• Hormonal surveillance: Regular testing for cortisol, androgens, and aldosterone in functional tumors.

• Mitotane monitoring: Therapeutic drug monitoring required for dose adjustment.

• Survivorship care: Bone health, metabolic syndrome, and psychological support due to chronic hormone disturbances.

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7. Multidisciplinary Care

• Endocrinologists: For diagnosis and hormone management.

• Oncologic surgeons: For adrenalectomy and complex resections.

• Medical oncologists: For mitotane therapy and systemic treatment planning.

• Radiologists: For ongoing imaging surveillance.

• Pathologists: For staging and confirming histology.

• Palliative care specialists: For advanced disease symptom management.