What is the recommended treatment for thymoma, including surgery, radiotherapy, and systemic therapy?

Thymoma Treatment

Complete surgical resection via open thymectomy is the cornerstone of thymoma treatment, with postoperative radiotherapy (PORT) recommended for incompletely resected or advanced stage disease, and cisplatin-based chemotherapy reserved for neoadjuvant therapy in locally advanced tumors or when complete resection is uncertain. 1

Surgical Management

Standard Surgical Approach

• Open thymectomy via median sternotomy is the standard of care for all resectable thymomas, regardless of stage 1
• Minimally invasive approaches (video-assisted thoracic surgery) are not recommended as standard of care due to insufficient evidence for complete resection in advanced disease 1
• Complete (R0) resection with clear surgical margins is the primary goal and the most important prognostic factor 1, 2
• Total resection is strongly preferred over partial resection 1

Surgical Considerations by Stage

Stage I (Non-invasive):

• Surgery alone is sufficient; no adjuvant therapy needed 1

Stage II:

• Complete surgical resection is standard 1
• Adjuvant radiation is not routinely recommended for completely resected Stage IIA disease 1
• Consider radiation only for high-risk features: capsular invasion (Stage IIB), close margins, WHO grade B histology, or pericardial adherence 1

Stage III (Locally Advanced):

• Surgery should be considered initially or after neoadjuvant therapy 1
• If complete resection appears unfeasible preoperatively, neoadjuvant chemotherapy or chemoradiotherapy should be given first 1
• Place surgical clips to mark areas of concern for guiding PORT 1
• Unilateral phrenic nerve resection is acceptable; bilateral phrenic nerve resection is contraindicated due to severe respiratory morbidity 1

Stage IVa (Pleural/Pericardial Metastases):

• Surgery recommended only if all pleural and pericardial metastases can be completely resected 1
• Multimodality therapy evaluation is mandatory 1

Referral Considerations

• Patients with suspected unresectable Stage III or IVa disease must be discussed at a multidisciplinary cancer conference (MCC) and considered for referral to high-volume tertiary thoracic surgical centers 1

Neoadjuvant Therapy

When to Use Neoadjuvant Therapy

• Indicated when complete resection appears unfeasible based on preoperative imaging 1
• All neoadjuvant therapy decisions should be discussed at MCC 1
• Histologic confirmation is required before initiating any neoadjuvant therapy 1

Neoadjuvant Regimen Options

• Cisplatin-based combination chemotherapy is the reasonable standard option 1
• Concurrent chemoradiotherapy is an alternative, particularly for small treatment volumes 1
• Sequential therapy (chemotherapy followed by radiation) is preferred for bulky tumors 1
• The optimal regimen for minimizing morbidity/mortality while maximizing resectability is not yet established 1

Important Caveat

• Evidence suggests neoadjuvant chemotherapy improves R0 resection rates, but the impact on overall survival remains unknown 1

Postoperative Radiotherapy (PORT)

Stage-Specific PORT Recommendations

Stage I:

• PORT is not recommended 1

Stage II:

• Not routinely recommended for completely resected disease 1
• Consider only for high-risk features (see surgical section above) 1
• Discuss risks of secondary malignancies and coronary artery disease, especially in younger patients 1

Stage III (Thymoma):

• PORT could be offered if no neoadjuvant radiotherapy was given 1
• The evidence shows moderate benefit with trivial acute harm 1

Stage III (Thymic Carcinoma):

• PORT should be offered if no neoadjuvant radiotherapy was given 1
• Evidence suggests larger survival benefit in thymic carcinoma compared to thymoma 1

Stage IVa:

• PORT should be offered if no neoadjuvant radiotherapy was given 1
• Benefits outweigh potential harm in advanced disease 1

Critical PORT Principle

• If neoadjuvant radiotherapy was given, PORT is not recommended to avoid excessive radiation toxicity 1

Adjuvant Chemotherapy

Thymoma

• Not routinely recommended for Stage I-II disease 1
• For Stage III thymoma, adjuvant chemotherapy should only be considered after MCC discussion if no neoadjuvant chemotherapy was given 1

Thymic Carcinoma

• For Stage III-IVa thymic carcinoma, adjuvant chemotherapy should be considered after MCC discussion for patients with advanced stages and poor prognosis 1
• Evidence is very low certainty but suggests small survival benefit with moderate acute toxicity 1
• Neoadjuvant chemotherapy is preferred over adjuvant when feasible, to improve R0 resection rates 1

Unresectable Disease

Treatment Approach

• Chemotherapy concurrent with, or sequential to, radiotherapy is recommended when surgery is not feasible 1
• Cisplatin-based combination chemotherapy is the standard systemic option 1

Definition of Unresectability

• Generally defined as extensive tumor involving middle mediastinal organs (trachea, great arteries, heart) that does not respond to cisplatin-based chemotherapy 1
• For Stage IVa, includes extensive bilateral pleural disease, pericardial metastases, or extrathoracic metastases 1

Stage IVb (Distant Metastases)

• This is a heterogeneous group requiring individualized MCC discussion based on extent and location of metastases 1
• Cisplatin-based chemotherapy is appropriate 1
• Radiotherapy may be appropriate for life-threatening situations 1
• Octreotide alone or with corticosteroids may be reasonable for recurrent cases 1

Medically Inoperable Patients

• For patients unfit for surgery at any stage, chemoradiation or radiation alone should be considered 1, 3

Common Pitfalls to Avoid

• Never perform bilateral phrenic nerve resection due to severe respiratory morbidity 1
• Do not assume benignity based on imaging alone; surgical resection provides definitive diagnosis 3
• Avoid minimally invasive approaches as standard in advanced disease where complete resection is critical 1
• Do not give both neoadjuvant radiotherapy and PORT to the same patient 1
• Remember that response rates to chemotherapy do not consistently correlate with survival in thymoma 1