What is the prognosis for an adult patient with malignant melanoma that has metastasized to the lung and adrenals?

Prognosis for Metastatic Melanoma to Lung and Adrenals

The prognosis for malignant melanoma with metastases to both the lung and adrenal glands is poor, with historical median survival of 6-9 months without treatment, but modern immunotherapy with checkpoint inhibitors (pembrolizumab or nivolumab) or targeted therapy (for BRAF-mutated tumors) offers the potential for median survival exceeding 10-11 months and durable long-term remission in 15-20% of patients. 1, 2, 3

Prognostic Considerations

Multiple metastatic sites indicate advanced stage IV disease with worse prognosis than isolated lung metastases alone. The presence of both lung and adrenal involvement represents disseminated disease that is not amenable to surgical resection. 1, 3

Historical Survival Data

• Stage IV melanoma with distant metastases historically carries a median survival of 6-9 months and long-term survival of less than 10% without modern systemic therapy 1, 3
• Isolated lung metastases treated with complete surgical resection combined with immunotherapy achieved 5-year survival rates of 27-39% in highly selected patients 1, 3
• However, your patient with both lung AND adrenal involvement is not a surgical candidate and falls into the poor prognostic category requiring systemic therapy 1

Modern Treatment Outcomes

• Ipilimumab (anti-CTLA-4 antibody) improved median overall survival to 10-11.2 months in previously treated patients, with 15-20% achieving durable long-term responses 1
• Pembrolizumab (anti-PD-1 antibody) is FDA-approved for unresectable or metastatic melanoma and has demonstrated superior outcomes 2
• Nivolumab (anti-PD-1 antibody) is another approved checkpoint inhibitor option 4, 5

Treatment Recommendations

Systemic therapy with checkpoint inhibitors is the treatment of choice for this patient with multiple metastatic sites. 1, 2, 4

First-Line Systemic Therapy Options

Obtain BRAF mutation testing immediately to determine eligibility for targeted therapy, as this is crucial for treatment selection. 1

• For BRAF-mutated melanoma: BRAF/MEK inhibitor combination therapy is indicated and can significantly improve outcomes 1, 6
• For BRAF wild-type or while awaiting mutation results: Initiate checkpoint inhibitor immunotherapy 1, 2, 4

Specific Immunotherapy Regimens

Pembrolizumab as a single agent is FDA-approved for unresectable or metastatic melanoma and represents a standard first-line option. 2

Nivolumab monotherapy or combination nivolumab plus ipilimumab are alternative regimens, with combination therapy offering enhanced T-cell function and improved anti-tumor responses compared to either antibody alone. 4

Role of Surgery

Surgical resection of multiple metastases is NOT appropriate in this clinical scenario. 1 Complete surgical resection is only considered for oligometastatic disease (1-3 lesions) if technically feasible with acceptable morbidity, which does not apply to your patient with both lung and adrenal involvement. 1

Critical Clinical Pitfalls

Adrenal Metastases Considerations

• Adrenal metastases from melanoma are found in approximately 50% of autopsy cases and are typically asymptomatic 7
• Primary adrenal insufficiency is rare but can occur, particularly as an immune-related adverse event from checkpoint inhibitor therapy (ipilimumab, nivolumab) 5, 7
• Monitor for symptoms of adrenal insufficiency (fatigue, weakness, hypotension, electrolyte abnormalities) both from metastatic disease and as a treatment-related toxicity 5

Immunotherapy-Related Endocrinopathies

Checkpoint inhibitors commonly cause immune-related endocrinopathies including hypothyroidism, hyperthyroidism, primary adrenal insufficiency, insulin-dependent diabetes, and hypophysitis. 5 Baseline endocrine function testing and ongoing monitoring throughout treatment is essential. 5

Treatment Response Monitoring

• Modern immunotherapies and targeted agents have the potential to achieve long-term remission in a larger proportion of patients than historical data suggest 1
• Overall survival is now 2 years or above with hope for cure in some cases, representing a dramatic improvement from the pre-2011 era 6

Palliative Considerations

For symptomatic metastases, stereotactic body radiation therapy (SBRT) or palliative radiation can be considered for local control while continuing systemic therapy. 1