What is the standard staging system and treatment approach for melanoma?

Melanoma Staging and Treatment Approach

The American Joint Committee on Cancer (AJCC) TNM classification system (8th edition) is the standard staging system for melanoma, with treatment approaches tailored to stage including wide local excision for localized disease, sentinel lymph node biopsy for intermediate thickness tumors, and systemic therapies for advanced disease. 1

Staging System

TNM Classification Components

• T (Primary Tumor): Based on tumor thickness (Breslow depth) measured to the nearest 0.1mm and presence of ulceration 1, 2

  • T1a: <0.8 mm without ulceration
  • T1b: 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration
  • Mitotic rate is no longer a T category criterion in the 8th edition but remains an important prognostic factor 2

• N (Regional Lymph Nodes): Based on number of metastatic nodes and presence of satellite/in-transit metastases 1, 2

  • Terms "microscopic" and "macroscopic" replaced with "clinically occult" and "clinically apparent" 2
  • Microsatellites, satellites, or in-transit metastases categorized as N1c, N2c, or N3c based on number of tumor-involved lymph nodes 2

• M (Distant Metastases): Based on site of metastases and serum LDH levels 1, 2

  • M1 subcategories include descriptors for LDH level (elevated LDH no longer automatically upstages to M1c) 2
  • M1d designation added for central nervous system metastases 2

Stage Grouping

• Stage 0: Melanoma in situ 1
• Stage I-II: Localized disease with varying thickness and ulceration status 1
• Stage III: Regional nodal metastases or in-transit/satellite metastases 1
  • Expanded from 3 to 4 subgroups (IIIA-IIID) based on N category and T category criteria 2
• Stage IV: Distant metastases 1

Treatment Approach by Stage

Primary Tumor Management

• Wide Local Excision (WLE) with safety margins based on tumor thickness 1:
  • 0.5 cm for in situ melanomas
  • 1 cm for tumors ≤2 mm thick
  • 2 cm for tumors >2 mm thick
  • Modifications may be needed for preservation of function in acral and facial melanomas 1

Regional Disease Management

• Sentinel Lymph Node Biopsy (SLNB) recommended for:

  • Intermediate thickness melanomas (>1 mm)
  • Thinner melanomas with adverse features (ulceration, high mitotic rate) 1
  • Provides important staging information and guides treatment decisions 1

• Complete Lymph Node Dissection considerations:

  • May be indicated for patients with clinically apparent nodal disease 1
  • Role after positive SLNB has evolved with recent clinical trials 1

Advanced Disease Management

• Molecular Testing for actionable mutations:

  • Mandatory for resectable or unresectable stage III or IV disease 1
  • BRAF testing is mandatory; if BRAF wild-type, testing for NRAS and c-kit mutations is recommended 1
  • Different melanoma subtypes have different mutation profiles:
    • Cutaneous: BRAF, CDKN2A, NRAS, TP53
    • Acral: BRAF, NRAS, NF1, KIT (lower frequencies)
    • Mucosal: SF3B1 1

• Systemic Therapy Options:

  • Immunotherapy: Anti-PD-1 agents (nivolumab, pembrolizumab) have shown significant survival benefits 3

    • Nivolumab demonstrated improved recurrence-free survival in adjuvant setting for resected stage IIB/C and III/IV melanoma 3

  • Targeted Therapy: For patients with BRAF mutations 1

  • Adjuvant Therapy: Consider for high-risk resected disease 3

Clinical Evaluation and Follow-up

• Initial Evaluation:

  • Complete skin examination and attention to lymph node drainage basins 1
  • Imaging studies based on stage - not necessary for low-risk melanomas (tumor thickness <1 mm) but recommended for higher stages 1, 4

• Follow-up:

  • Lifelong surveillance recommended due to risk of recurrence and second primary melanomas 4
  • Higher intensity follow-up during first 5 years when risk of relapse is highest 4
  • Personalized approach based on patient's risk factors 4

Common Pitfalls and Caveats

• Mitotic rate is no longer used for T1 staging but remains an important prognostic factor that should still be reported 1, 2

• Proper documentation of sentinel node findings is critical - record size and location of tumor in positive nodes 1

• PD-L1 expression can be useful to assess but has limited clinical utility at this time 1

• Melanoma subtypes (cutaneous, acral, mucosal) have different mutation profiles and may require different treatment approaches 1

• Avoid unnecessary imaging in low-risk patients, which can increase anxiety without improving outcomes 4