What are the stages of melanoma and their corresponding treatments?

Melanoma Stages and Treatment

Melanoma is staged from 0 to IV based on the AJCC 8th edition TNM classification system, with treatment ranging from simple excision for early-stage disease to systemic immunotherapy and targeted therapy for advanced stages. 1

Staging Classification

Stage 0 (Melanoma in Situ)

• Confined to the epidermis with no invasion 1
• Treatment: Wide excision with 0.5 cm margins 1
• No follow-up required after excision 2

Stage I-II (Localized Disease)

These stages are defined by tumor thickness (Breslow depth) and ulceration status, with no evidence of regional or distant metastases 2, 1:

Stage IA:

• Tumor <0.8 mm without ulceration 3
• Treatment: Wide excision with 1 cm margins 2, 1
• Follow-up: 2-4 visits over 12 months, then discharge 2

Stage IB:

• Tumor 0.8-1.0 mm with or without ulceration, OR <0.8 mm with ulceration 3
• Treatment: Wide excision with 1 cm margins + consider sentinel lymph node biopsy (SLNB) 2, 1
• Follow-up: Every 3 months for 3 years, then every 6 months to 5 years 2

Stage IIA:

• Tumor 1.01-2.0 mm with ulceration OR 2.01-4.0 mm without ulceration 1
• Treatment: Wide excision with 1-2 cm margins + SLNB 2, 1
• Follow-up: Every 3 months for 3 years, then every 6 months to 5 years 2

Stage IIB:

• Tumor 2.01-4.0 mm with ulceration OR >4.0 mm without ulceration 1
• Treatment: Wide excision with 2-3 cm margins + SLNB 2, 1
• Adjuvant therapy: Anti-PD-1 immunotherapy (pembrolizumab or nivolumab) for 52 weeks improves recurrence-free survival 4
• Follow-up: Every 3 months for 3 years, every 6 months to 5 years, then annually to 10 years 2

Stage IIC:

• Tumor >4.0 mm with ulceration 1
• Treatment: Wide excision with 3 cm margins + SLNB 2, 1
• Adjuvant therapy: Anti-PD-1 immunotherapy (pembrolizumab or nivolumab) for 52 weeks 4
• Follow-up: Every 3 months for 3 years, every 6 months to 5 years, then annually to 10 years 2

Stage III (Regional Nodal/In-Transit Disease)

Characterized by regional lymph node metastases or in-transit/satellite metastases 2, 1:

Stage IIIA:

• Clinically occult nodal disease with favorable primary tumor features 3
• Treatment: Wide excision + complete lymph node dissection 5
• Imaging: CT not routinely required; avoid routine PET/CT 2, 6
• Adjuvant therapy: Anti-PD-1 immunotherapy (nivolumab or pembrolizumab) for 52 weeks OR BRAF/MEK inhibitors (dabrafenib + trametinib) if BRAF-mutated 5, 4
• Follow-up: Every 3 months for 3 years, every 6 months to 5 years 2

Stage IIIB:

• Clinically occult nodal disease with adverse primary tumor features OR clinically apparent nodal disease with favorable features 3
• Treatment: Wide excision + complete lymph node dissection 5
• Imaging: CT chest/abdomen/pelvis prior to surgery mandatory 2, 6
• Adjuvant therapy: Anti-PD-1 immunotherapy (nivolumab or pembrolizumab) for 52 weeks OR BRAF/MEK inhibitors if BRAF-mutated 5, 4
• Consider adjuvant radiation therapy for high-risk features (multiple positive nodes, large nodes, extranodal extension) 5
• Follow-up: Every 3 months for 3 years, every 6 months to 5 years, then annually to 10 years 2

Stage IIIC:

• Clinically apparent nodal disease with adverse primary tumor features 3
• Treatment: Wide excision + complete lymph node dissection 5
• Imaging: CT chest/abdomen/pelvis prior to surgery mandatory 2, 6
• Adjuvant therapy: Anti-PD-1 immunotherapy (nivolumab or pembrolizumab) for 52 weeks OR BRAF/MEK inhibitors if BRAF-mutated 5, 4
• Strongly consider adjuvant radiation therapy 5
• Follow-up: Every 3 months for 3 years, every 6 months to 5 years, then annually to 10 years 2

Stage IIID:

• Most advanced regional disease 3
• Management identical to Stage IIIC 5

Stage IV (Distant Metastatic Disease)

Presence of distant metastases to skin, soft tissue, distant lymph nodes, lung, or other visceral sites 2, 1:

Treatment approach:

• First-line systemic therapy: Dual checkpoint blockade with ipilimumab (anti-CTLA-4) + nivolumab (anti-PD-1) 4
• Alternative: BRAF/MEK inhibitor combination therapy (dabrafenib + trametinib OR encorafenib + binimetinib) if BRAF V600 mutation present 1
• Molecular testing mandatory: BRAF, NRAS, c-KIT mutations 1
• Surgery: Consider for oligometastatic disease (skin, brain, gut) or to prevent pain/ulceration 2
• Radiation therapy: Palliative role for symptomatic metastases 2
• Imaging: CT chest/abdomen/pelvis and brain MRI as clinically indicated; measure LDH 2, 6
• Follow-up: Every 3 months for 2 years, then every 6 months for 3 years per clinical need 6

Critical Staging Workup Elements

Pathology report must include: 2

• Breslow thickness (to nearest 0.1 mm, not 0.01 mm) 3
• Ulceration status 2
• Mitotic rate (number per mm²) 2
• Margins (deep and peripheral) 2
• Microsatellitosis if present (defines at least stage IIIB) 2
• Lymphovascular invasion 2

Sentinel lymph node biopsy indications: 2, 1

• Tumor thickness >1.0 mm (category 1 recommendation) 2
• Tumor thickness 0.8-1.0 mm (consider based on clinical context) 2, 4
• Tumor thickness <0.8 mm with ulceration or high mitotic rate 1

Common Pitfalls

Avoid these errors: 2, 1

• Do NOT perform routine imaging for Stage I, II, or IIIA disease—false-positive rate is high and true-positive yield is low 2
• Do NOT use mitotic rate for T1 staging anymore (removed in AJCC 8th edition), but still report it as prognostic factor 1, 3
• Do NOT perform wider margins on initial diagnostic biopsy—this interferes with sentinel node mapping 2
• Do NOT discharge Stage IB-II patients after initial excision without discussing SLNB 2
• Do NOT forget that microsatellitosis automatically defines at least Stage IIIB regardless of sentinel node status 2

Adjuvant Therapy Specifics

For Stage IIB-C and III disease: 5, 4

• Nivolumab 240 mg IV every 2 weeks OR 480 mg IV every 4 weeks for 52 weeks (12-month recurrence-free survival 70.5% vs 60.8% with ipilimumab) 5
• Pembrolizumab 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks for 52 weeks (12-month recurrence-free survival 75% vs 61% for placebo) 5
• Dabrafenib + trametinib for BRAF-mutated melanoma (HR for recurrence 0.52) 4