Is surgery indicated in metastatic melanoma?

Surgery in Metastatic Melanoma

Surgery is indicated for metastatic melanoma when disease is limited and resectable, particularly for solitary or oligometastatic sites, as complete resection can improve survival and potentially render patients disease-free. 1

Stage IV Disease: Resectability Determines Surgical Candidacy

The fundamental decision point in metastatic melanoma is whether disease is limited (resectable) versus disseminated (unresectable). 1

Limited Metastatic Disease (Resectable)

Complete surgical resection is recommended when feasible for limited metastatic disease. 1 This approach is supported by multiple guidelines and applies to:

• Solitary visceral metastases in parenchymal organs including the central nervous system 1
• Oligometastatic disease where R0 (tumor-free margin) resection is achievable 1
• Selected patients with good performance status and isolated tumor manifestations 1

Critical caveat: Before undertaking aggressive surgical intervention for a solitary visceral metastasis, a short observation period or systemic treatment followed by repeat imaging is appropriate to exclude the possibility that this represents the first of multiple metastatic sites. 1 This strategy helps better select patients who will truly benefit from surgical intervention rather than those with rapidly progressive disseminated disease.

Surgical Outcomes in the Modern Era

Surgery combined with effective systemic therapies (immunotherapy or targeted therapy) significantly improves survival compared to surgery alone. The most recent high-quality evidence demonstrates:

• Responders to systemic therapy who underwent metastasectomy had median overall survival of 84.3 months versus 42.9 months for responders without surgery (P = 0.018) 2
• Median survival after surgery improved from 6 months (pre-immunotherapy era) to 16 months (post-immunotherapy era) (P < 0.001) 3
• Treatment with immune checkpoint inhibitors was independently associated with prolonged survival (HR 0.38, P < 0.001) 3

Stage III: In-Transit Metastases

For single or small numbers of in-transit metastases, complete surgical excision with histologically negative margins is the preferred approach (category 2B). 1

• Sentinel lymph node biopsy can be considered during curative resection of solitary in-transit metastasis due to high probability of occult nodal involvement, though its impact on outcome is unproven (category 2B). 1
• For unresectable in-transit metastases, hyperthermic isolated limb perfusion or infusion is an option (category 2B). 1

Disseminated Disease: Palliative Surgery

For disseminated unresectable disease, surgery shifts to a palliative role for symptom management including:

• Gastrointestinal bleeding or obstruction 1
• Ulcerated soft tissue cutaneous metastases 1
• Bulky adenopathy 1
• Symptomatic brain or bone metastases 1

Clinical trials remain the preferred treatment option for patients with distant metastatic disease. 1

Evolving Surgical Indications

Novel indications for surgery have emerged in the immunotherapy era, including:

• Resection of residual oligometastatic disease after response to systemic therapy (15.9% of operations versus 4.3% pre-immunotherapy, P = 0.045) 3
• Increased abdominal metastasectomies (21.1% versus 4.2% pre-immunotherapy, P < 0.001) 3
• Decreased in-transit excisions (0.9% versus 19.4% pre-immunotherapy, P < 0.001), reflecting better systemic control 3

Key Surgical Principles

In all surgically treated metastatic melanoma patients, R0 resections (complete excision with tumor-free margins) must be the goal. 1 Incomplete resection should be treated as disseminated disease with systemic therapy. 1

Detailed staging investigation with CT or PET scans is necessary before aggressive local surgical treatments to exclude additional metastases. 1

Common Pitfalls to Avoid

• Do not operate on apparent solitary metastases without observation period or repeat imaging to exclude rapidly progressive disease 1
• Do not pursue surgery if R0 resection is not achievable—residual disease negates survival benefit 1
• Do not delay systemic therapy for marginal surgical candidates—clinical trials or immunotherapy should take priority in disseminated disease 1
• Brain metastases usually require priority treatment to prevent hemorrhage, seizures, or neurologic dysfunction before addressing extracranial disease 1