Should an elderly female patient with a suspected adrenal gland tumor start chemotherapy and/or immunotherapy before surgery?

Neoadjuvant Chemotherapy/Immunotherapy for Suspected Adrenal Tumor

Surgery is the primary and definitive treatment for adrenal tumors, and neoadjuvant chemotherapy or immunotherapy should NOT be initiated before surgical resection in the vast majority of cases. 1, 2, 3

Primary Treatment Approach

Complete surgical excision (R0 resection) is the only curative treatment for adrenal tumors and should be performed as soon as the patient is medically optimized. 1, 2 The decision pathway depends on:

1. Hormonal Status Assessment (Must Be Done First)

• Screen for pheochromocytoma immediately with plasma or urine metanephrines, as this is a surgical emergency that requires specific preoperative preparation 1, 2
• Measure serum cortisol after 1 mg dexamethasone suppression test to evaluate for cortisol-secreting adenoma 1
• Check plasma aldosterone and renin activity if hyperaldosteronism is suspected 1

2. Imaging Characteristics to Guide Surgical Approach

• Laparoscopic adrenalectomy is the gold standard for tumors <5-6 cm without invasion 1, 3
• Open adrenalectomy is mandatory for masses >5 cm, irregular morphology, heterogeneity, local invasion, or suspected adrenocortical carcinoma (ACC) 1, 3
• CT features suggesting malignancy include: size >4 cm, heterogeneity, irregular margins, lipid-poor appearance, poor contrast washout, and evidence of invasion or necrosis 1

When Neoadjuvant Therapy May Be Considered (Rare Exceptions)

Neoadjuvant chemotherapy should only be considered in the rare scenario of inoperable locally infiltrating or metastatic ACC, where surgical excision becomes feasible after objective response to chemotherapy. 1 This represents a highly selective exception, not standard practice.

Critical Contraindications to Neoadjuvant Therapy:

• Functional tumors (pheochromocytoma, cortisol-secreting, aldosterone-secreting) require urgent surgical resection after appropriate medical preparation 1, 2
• Delaying surgery for chemotherapy in resectable disease worsens outcomes 1
• Immunotherapy has no established role in adrenal tumors and is frequently ineffective for adrenal metastases 4

Preoperative Medical Optimization (Not Chemotherapy)

For Pheochromocytoma:

• Initiate alpha-adrenergic blockade (phenoxybenzamine 10 mg twice daily or doxazosin) for 10-14 days before surgery 1, 2
• Target blood pressure <130/80 mmHg supine and systolic >90 mmHg standing 1, 2
• Add beta-blocker only after alpha-blockade if tachyarrhythmias develop 1

For Cortisol-Secreting Tumors:

• Administer hydrocortisone 150 mg/day during surgery and postoperatively to prevent adrenal crisis 1
• Postoperative corticosteroid supplementation is required until HPA axis recovery 1

Surgical Timing Considerations for Elderly Patients

Age alone is not a contraindication to adrenalectomy in elderly patients, though operative mortality increases with certain conditions. 5 The Goldman multifactorial cardiac risk scheme reliably predicts postoperative outcomes in elderly patients 5:

• Goldman class II or greater predicts increased morbidity and mortality 5
• Operative mortality for benign functional tumors (pheochromocytoma, hyperaldosteronism) is minimal even in elderly patients 5
• Adrenocortical carcinoma has significantly higher operative mortality (43%) in elderly patients 5

Critical Pitfalls to Avoid

• Never perform biopsy on a suspected pheochromocytoma—this can precipitate fatal hypertensive crisis 1, 2
• Do not delay surgery for chemotherapy in resectable disease, as this worsens recurrence rates and survival 1
• Laparoscopic approach is contraindicated for ACC >5 cm due to significantly higher recurrence rates and carcinomatosis with minimally invasive approaches 1
• Bilateral adrenalectomy requires lifelong glucocorticoid and mineralocorticoid replacement 6

Postoperative Adjuvant Therapy (Not Preoperative)

Adjuvant mitotane should be considered after complete resection of ACC to delay or prevent recurrence. 1 Adjuvant radiotherapy is indicated for incomplete (R1) or uncertain (Rx) resection margins 1.