What is the recommended management of thymoma based on Masaoka‑Koga stage and the presence of associated myasthenia gravis?

Management of Thymoma Based on Masaoka-Koga Stage and Myasthenia Gravis Status

Surgery with complete resection is the cornerstone of thymoma management for all resectable stages, with postoperative radiotherapy added for stage II-IV disease or positive margins, while myasthenia gravis requires mandatory neurologist consultation and medical optimization before any surgical intervention. 1

Pre-Treatment Evaluation and Myasthenia Gravis Assessment

All patients with suspected thymoma must undergo systematic evaluation for myasthenia gravis before proceeding to surgery, regardless of symptoms. 2, 3

• Measure serum anti-acetylcholine receptor antibody levels in every patient to avoid respiratory failure during anesthesia, even in asymptomatic individuals 3
• Complete immunological workup including CBC with reticulocytes, serum protein electrophoresis, anti-acetylcholine receptor antibodies, and anti-nuclear antibodies 1
• Standard imaging is IV contrast-enhanced CT scan of the thorax from apex to costodiaphragmatic recesses 1, 3
• If myasthenia gravis is detected, neurologist consultation and medical optimization are mandatory before surgery to prevent perioperative respiratory complications 2, 3, 4

Critical Pitfall to Avoid

Do not proceed to surgery without checking anti-acetylcholine receptor antibodies, as 30-50% of thymoma patients have myasthenia gravis, and approximately 20% of mortality in thymoma patients is directly attributable to myasthenia gravis itself rather than the tumor. 2, 3

Surgical Management by Masaoka-Koga Stage

Stage I (Encapsulated, No Invasion)

Complete surgical resection via median sternotomy with total thymectomy is the definitive treatment, with no postoperative therapy required. 1

• Complete thymectomy including tumor, residual thymus gland, and perithymic fat is preferred 1
• Thymomectomy alone (leaving residual thymic tissue) is an option only in stage I tumors in non-myasthenic patients 1
• For completely resected (R0) stage I disease with no capsular invasion, postoperative therapy is not recommended 1
• 10-year survival rate is approximately 90% with complete resection 3, 5
• Minimally invasive surgery is an option for presumed stage I tumors in the hands of appropriately trained thoracic surgeons, but should not compromise complete resection 1

Stage II (Microscopic Invasion into Capsule or Mediastinal Fat)

Complete surgical resection followed by consideration of postoperative radiotherapy is recommended. 1

• Complete thymectomy with en bloc removal is the standard approach 1
• Postoperative RT can be considered for stage II disease, though historically controversial 1
• RT dose of 45-50 Gy is recommended for clear or close margins 1
• 10-year survival rate is approximately 70% with complete resection 3
• Mark areas of uncertain margins with clips during surgery to allow precise delivery of postoperative radiotherapy 1

Important caveat: Mediastinal recurrence has been documented in stage II patients initially considered to have noninvasive disease by the surgeon, supporting the recommendation for postoperative radiotherapy and minimum 10-year follow-up. 5

Stage III (Macroscopic Invasion into Neighboring Organs)

Complete surgical resection with en bloc removal of all affected structures followed by postoperative radiotherapy is the standard approach. 1

• En bloc removal of all affected structures including lung parenchyma (usually limited resection), pericardium, venous great vessels, nerves, and pleural implants should be carried out 1
• Postoperative RT is strongly recommended for stage III disease regardless of resection margin status, as it significantly improves 5-year overall survival 1
• RT dose of 45-50 Gy for clear/close margins; 54 Gy for microscopically positive margins 1
• For positive margins, postoperative RT alone or in combination with chemotherapy is recommended 1
• Phrenic nerve preservation does not affect overall survival but increases risk of local recurrence; however, bilateral phrenic nerve resection should be avoided due to severe respiratory morbidity 1, 3
• 10-year survival rate drops to approximately 20-60% depending on completeness of resection 5, 6

Stage IV (Pleural or Pericardial Dissemination or Lymphogenous/Hematogenous Metastasis)

Multidisciplinary team evaluation is mandatory to determine resectability, with treatment approach varying based on extent of disease. 1

Stage IVA (Pleural/Pericardial Dissemination):

• For solitary metastasis or ipsilateral pleural metastasis that is resectable: surgery followed by RT 1
• For medically inoperable/unresectable disease: systemic therapy with consideration of observation 1
• Postoperative RT significantly improves 5-year overall survival for stage IV disease regardless of resection margin status 1

Stage IVB (Lymphogenous/Hematogenous Metastasis):

• Systemic therapy is the primary approach 1
• Consider local therapies including image-guided thermal ablation or RT for specific lesions 1
• Surgery may be considered for resectable disease in highly selected patients 1

Advanced, Metastatic, or Recurrent Disease

Multidisciplinary team evaluation is essential, with surgery recommended if disease is resectable and patient is medically operable, followed by postoperative RT or systemic therapy. 1

• Complete (R0) resection remains a critical prognostic factor even in advanced disease 1
• For potentially resectable disease where complete resection is uncertain, preoperative systemic therapy (combination chemotherapy) may be used to reduce tumor size 1
• RT (with or without chemotherapy) is an option for unresectable disease, with concurrent chemoradiation showing objective response rates of 85.7% in prospective studies 1

Special Considerations for Myasthenia Gravis

Thymectomy is mandatory in all patients with thymoma regardless of myasthenia gravis status, as it is both an oncological necessity and may substantially reduce myasthenia gravis symptoms. 3, 4

• Complete thymectomy is preferred over partial resection in myasthenia gravis patients, as local recurrences have been observed after partial procedures 4
• Neurologist consultation and treatment optimization must occur before surgical resection 2, 3, 4
• Particular care with anesthetic agents is required given potential respiratory muscle weakness 4

Prognostic Impact of Myasthenia Gravis

The presence of myasthenia gravis affects survival outcomes. Research shows that 5-year overall survival in patients with myasthenia gravis is 76.0% compared to 89.1% in patients without myasthenia gravis, and multivariate analysis confirms myasthenia gravis as an independent prognostic factor. 7 However, older guideline data suggests myasthenia gravis is no longer considered an adverse factor in survival when properly managed. 5 Given this conflicting evidence, aggressive preoperative optimization of myasthenia gravis is critical to minimize perioperative complications.

Radiation Therapy Principles

Radiation therapy should be delivered by radiation oncologists with experience in managing thymomas, incorporating 4D-CT for motion assessment. 1

• Entire thymic region should be treated including sites of spread (pericardium, pleura) 1
• 45-50 Gy for clear or close margins 1
• 54 Gy for microscopically positive resection margins 1
• 60-70 Gy (1.8-2 Gy/fraction per day) for gross residual disease after surgery 1
• Close communication between radiation oncologists and surgeons about operative findings is essential to determine target volume at risk 1

Key Surgical Principles Across All Stages

• Median sternotomy is the standard approach 1
• Complete thymectomy including tumor, residual thymus gland, and perithymic fat is the goal 1
• Resection should be performed by board-certified thoracic surgeons with primary focus on thoracic oncology 3
• Avoid preoperative biopsy if resectable thymoma is strongly suspected, as small biopsies cannot determine invasion status and risk pleural seeding if transpleural approach is used 1, 3
• Frozen sections to assess tumor involvement of resection margins are not recommended 1
• For widely extensive invasive disease (stage III/IV), en bloc removal of all affected structures is required 1

Surveillance and Follow-Up

All patients should be followed for a minimum of 10 years, as recurrences can occur late. 5

• The duration for surveillance has not been definitively established, but long-term follow-up is essential 1
• Stage II and III patients should receive postoperative radiotherapy and close surveillance 5
• For type B3 thymoma specifically, 5-year freedom from recurrence rates are 91% overall, but 10-year rates drop to 73%, emphasizing need for extended follow-up 6