What are the systemic treatment options for a patient with pleomorphic adenoma (benign salivary gland tumor) with lung metastasis?

Systemic Treatment for Metastasizing Pleomorphic Adenoma of the Lung

Surgical metastasectomy is the primary treatment for metastasizing pleomorphic adenoma with lung involvement, as systemic chemotherapy and radiotherapy have demonstrated limited efficacy for this rare entity. 1

Understanding the Disease Entity

Metastasizing pleomorphic adenoma (MPA) is an exceptionally rare malignancy where histologically benign salivary gland tumors produce distant metastases, most commonly to bone (36.6%), lung (33.8%), and neck lymph nodes (20.1%). 2 This entity differs fundamentally from pleomorphic carcinoma of the lung, which is a primary lung malignancy with different treatment paradigms. 3

Primary Treatment Approach: Surgical Resection

Metastasectomy confers significant survival advantage over nonoperative treatment and should be pursued when technically feasible. 1 The evidence demonstrates:

• 5-year disease-specific survival of 58% and disease-free survival of 50% with surgical management 1
• Surgical treatment with proper follow-up results in longer survival compared to non-surgical approaches 3, 1
• Complete surgical resection should be pursued when feasible, particularly when metastatic deposits are limited 4, 1

Criteria for Surgical Consideration

Proceed with metastasectomy when: 4

• Complete surgical resection is technically feasible
• Time to pulmonary relapse after primary tumor treatment is ≥36 months (extrapolated from adenoid cystic carcinoma data for salivary gland tumors)
• Patient has adequate performance status and medical fitness

Role of Systemic Therapy

Systemic chemotherapy and radiotherapy have demonstrated limited value in metastasizing pleomorphic adenoma. 1 However, systemic therapy may be considered in specific circumstances:

Indications to Initiate Systemic Therapy

Consider systemic therapy when: 4

• Metastatic deposits are symptomatic and not amenable to palliative local therapy
• Growth has potential to compromise organ function
• Lesions have grown more than 20% in the preceding 6 months
• Multiple metastatic sites preclude complete surgical resection

Systemic Treatment Options

For salivary gland malignancies with metastatic disease (when MPA behaves aggressively): 4

Targeted therapy based on tumor molecular alterations may be offered if clinical trial unavailable:

• Multitargeted tyrosine kinase inhibitors (lenvatinib or sorafenib) for adenoid cystic carcinoma histology
• Molecular-directed therapy for specific alterations (AR, HER2, NTRK) in non-adenoid cystic tumors
• One case report documented partial response to gefitinib in pleomorphic carcinoma 3

Important caveat: No single-agent or combination chemotherapy has demonstrated survival advantage in metastatic salivary gland tumors, and no randomized trials compare treatment with supportive care alone. 4

Stereotactic Ablative Body Radiotherapy (SABR)

For lung metastases where surgical removal is technically difficult or medical contraindications exist, stereotactic ablative body radiotherapy is an emerging option. 4

• Local control at 6 and 24 months: 94.6% and 78.9% respectively 4
• Median overall survival: 34.7 months in oligometastatic disease 4
• Requires 1-5 metastatic lesions, controlled primary tumor, and all sites safely treatable 4, 5

Prognostic Factors and Monitoring

Poor prognostic indicators include: 1

• Development of distant lesions within 10 years of primary tumor
• Presence of metastases in multiple sites
• Both are independent predictors of survival

Mean latency from primary tumor to metastasis: 14.9 years (range 0-51 years) 2, with 72.8% of cases reporting local recurrence prior to metastasis. 2

Clinical Algorithm

1. Confirm diagnosis: Pathologic confirmation that metastatic lesions are histologically benign pleomorphic adenoma 6, 2

2. Assess resectability: Multidisciplinary evaluation for complete surgical resection feasibility 4

3. If resectable: Proceed with metastasectomy 1

4. If unresectable but oligometastatic (1-5 lesions): Consider SABR 4, 5

5. If symptomatic or rapidly progressive (>20% growth in 6 months): Consider systemic therapy with molecular-directed agents if available 4

6. If asymptomatic with minimal disease burden: Observation with close monitoring may be appropriate 4

Critical Pitfalls to Avoid

• Do not assume standard lung cancer chemotherapy regimens will be effective - MPA is fundamentally different from primary lung malignancies 1
• Do not delay surgical evaluation - metastasectomy provides the only proven survival benefit 1
• Do not overlook molecular testing - targeted therapies may offer benefit in select cases 4
• Ensure lifelong follow-up - recurrence can occur decades after initial treatment 7, 2