What is the treatment approach for pheochromocytoma?

Treatment Approach for Pheochromocytoma

Complete surgical resection (R0) is the mainstay of potentially curative treatment for pheochromocytoma, with mandatory preoperative alpha-adrenergic blockade for at least 10-14 days before surgery to prevent perioperative complications. 1

Preoperative Management

Alpha-Blockade (Essential First Step)

• Start alpha-adrenergic blockade 10-14 days before surgery 1
• Options include:
  • Non-selective α-blocker: Phenoxybenzamine (40-80 mg/day) 1, 2
  • Selective α1-blockers: Doxazosin, prazosin, or terazosin 1
• Start with low dose and gradually increase every 2-4 days 1
• Blood pressure targets: <130/80 mmHg when supine, systolic BP >90 mmHg when upright 1

Additional Preoperative Measures

• Beta-blockers: Add ONLY after adequate alpha-blockade if tachycardia or arrhythmias develop 1, 3
  • Never start beta-blockers before alpha-blockade (risk of hypertensive crisis) 1
• Calcium channel blockers: Can be used as adjunct therapy for refractory hypertension 1
• Volume expansion:
  • High-sodium diet
  • 1-2 liters saline infusion 24 hours before surgery
  • Compressive stockings to prevent orthostatic hypotension 1

Surgical Management

Surgical Approach

• Laparoscopic adrenalectomy: Recommended for small tumors (<8 cm) without invasion 1
• Open surgery: Recommended for:
  • Larger tumors (>5-6 cm)
  • Evidence of invasion
  • Should include locoregional lymphadenectomy 4, 1

Perioperative Considerations

• Close hemodynamic monitoring during surgery is crucial
• Medications for hypertensive crisis should be readily available:
  • Magnesium sulfate
  • Phentolamine
  • Nitroprusside
  • Nitroglycerin 1

Management of Metastatic Disease

Surgical Options

• Functional PPGLs (predominantly retroperitoneal) should be resected as an initial priority in patients with multifocal disease 4
• Limited role for palliative debulking in:
  • Locally aggressive, large tumors
  • High probability of incomplete surgical resection
  • Metastatic disease
  • Consider when patients are not responsive to medical management or have debilitating symptoms 4

Non-Surgical Options for Metastatic Disease

• Radiopharmaceuticals (131I-MIBG) 4
• Locoregional ablative procedures 4
• Combination chemotherapy (CVD: cyclophosphamide, vincristine, dacarbazine) 4, 5
• For SDHx-related metastatic disease: Consider temozolomide or tyrosine kinase inhibitors (TKIs) 4
• Anti-resorptive therapies for widespread bone metastases 4
• "Wait and see" policy recommended for low tumor burden and asymptomatic cases 4

Follow-up and Surveillance

• Immediate post-treatment:
  • Measure plasma or urine metanephrines by 8 weeks post-surgery
  • Imaging at 3-6 months post-surgery 1
• Long-term follow-up:
  • Continue for at least 10 years
  • Regular check-ups every 3-4 months for 2-3 years, then every 6 months 1
  • Annual biochemical measurements to detect recurrence or metastases 1
• Lifelong surveillance for:
  • Patients with genetic syndromes
  • Extra-adrenal primary disease
  • Tumor size >5 cm
  • SDHB mutations 1

Special Considerations

• Genetic testing should be considered in all patients, especially with:
  • Young age at diagnosis
  • Bilateral or multifocal disease
  • Extra-adrenal location
  • Family history of pheochromocytoma 1
• Multidisciplinary approach involving endocrinologists, surgeons, anesthesiologists, and genetic counselors is essential for optimal outcomes 6
• TKIs may worsen hypertension; careful follow-up and aggressive antihypertensive dosage adjustment is needed 4

By following this structured approach to pheochromocytoma treatment, focusing on preoperative stabilization, appropriate surgical intervention, and vigilant long-term follow-up, patient morbidity and mortality can be significantly reduced.