In an adult with stage IV cutaneous melanoma and limited (≤ 3–5 sites) resectable metastases and an ECOG (Eastern Cooperative Oncology Group) performance status of 0‑2, what is the role of surgery?

Role of Surgery in Stage IV Cutaneous Melanoma with Limited Resectable Metastases

In adults with stage IV cutaneous melanoma presenting with limited (≤3–5 sites) resectable metastases and good performance status (ECOG 0-2), complete surgical resection (R0 resection) of all metastatic sites should be pursued as a primary treatment modality, preferentially combined with adjuvant systemic immunotherapy or targeted therapy. 1, 2

Surgical Candidacy and Patient Selection

Surgery offers the only treatment capable of achieving complete pathologic response within days and has historically been associated with the highest survival rates in stage IV melanoma. 2, 3

Key Selection Criteria:

• Oligometastatic disease (≤3–5 resectable sites) with no evidence of additional unresectable metastases on comprehensive staging 1, 2
• Good performance status (ECOG 0-2) indicating fitness for surgical intervention 1
• Slow-growing disease characterized by long disease-free interval after primary treatment 2
• Technical feasibility of achieving R0 (complete) resection of all metastatic sites 1

Critical Pre-Operative Workup:

• Exhaustive imaging with PET/CT and MRI scans to exclude additional metastases before committing to surgery 2
• CT or PET scans are necessary to exclude presence of further metastases before undertaking aggressive local surgical treatments 1

Surgical Principles and Goals

Complete (R0) resection of all metastatic sites must be the goal—debulking surgery without complete resection should not be attempted as it does not improve survival. 1, 2

Anatomic Site-Specific Considerations:

• Visceral metastases: Surgery is appropriate for selected cases with isolated tumor manifestations and good performance status 1
• Brain metastases: Surgical removal or stereotactic radiosurgery should be considered for isolated CNS metastases 1
• In-transit metastases: Surgical excision with complete removal of all lesions is the standard treatment 1
• Locoregional lymph node metastases: Complete lymph node dissection (not isolated node removal) is indicated 1

Integration with Systemic Therapy

The therapeutic landscape has fundamentally shifted—surgery in metastatic melanoma is now part of a multidisciplinary treatment strategy rather than a standalone intervention. 4, 5

Adjuvant Therapy After Complete Resection:

• PD-1 checkpoint inhibitors (pembrolizumab or nivolumab) are recommended for all patients rendered no evidence of disease (NED) by surgery 1
• Combination nivolumab plus ipilimumab has shown very promising clinical activity in stage IV patients rendered NED by surgery or radiotherapy, though with increased toxicity 1
• For BRAF-mutated melanoma: Dabrafenib/trametinib combination is an alternative to PD-1 blockade after complete resection 1

Treatment Sequencing:

• Timing and sequencing of surgery in modern multimodal targeted treatment remains an evolving area requiring multidisciplinary discussion 2
• All stage IV patients need to be treated and discussed in an interdisciplinary tumor board at centers with broad experience 1

Evidence Quality and Historical Context

While no randomized controlled trials have validated complete surgery in stage IV disease, phase II data and numerous retrospective studies demonstrate clear and durable survival advantages for patients undergoing complete resection. 2, 3

Strength of Evidence:

• Guidelines from 2001 stated "with the possible exception of resection of slowly developing single metastases, there is no curative treatment" for stage IV disease 1
• More recent guidelines (2012,2019) explicitly recommend surgical removal of isolated metastases in fit patients as offering potential for long-term disease control 1
• The evolution reflects improved patient selection, surgical techniques, and availability of effective adjuvant systemic therapies 4, 5

Palliative Surgical Indications

Beyond curative intent, metastasectomy offers significant palliation in specific clinical scenarios:

• Gastrointestinal bleeding or obstruction from metastatic disease 2
• Symptomatic metastases causing pain or functional impairment 1
• Immediate tumor burden reduction with minimal morbidity and mortality at reasonable cost 3

Critical Pitfalls to Avoid

Do Not Proceed With Surgery If:

• Incomplete resection (R1 or R2) is anticipated—only complete resection improves survival 1, 2
• Rapidly progressive disease or short disease-free interval suggests aggressive biology unsuitable for surgical approach 2
• Multiple unresectable sites are present in addition to resectable disease 2
• Poor performance status (ECOG >2) increases surgical morbidity without survival benefit 1

Common Errors:

• Debulking surgery without achieving complete resection provides no survival benefit and should be avoided 2
• Proceeding without comprehensive staging risks leaving undetected metastases that negate surgical benefit 1, 2
• Failing to integrate systemic therapy in the modern era represents suboptimal care given proven adjuvant benefits 1, 4

Alternative to Surgery for Oligometastatic Disease

Stereotactic radiosurgery (particularly for brain metastases) is an alternative ablative approach that can achieve local control comparable to surgery in selected cases 1