Return to: Cancer Care Principles

see also: Sentinel Lymph Node Biopsy / Case Example Sentinel Lymph Node Biopsy and Melanoma Pathology Reporting Template

See individual protocols by stage:

Stage 0: TisN0M0 Melanoma in situ, lentigo maligna (8th Edition AJCC)

Stage IA cT1aN0M0: T1a: Breslow <0.8 mm, no ulceration (U-)

Stage IA T1N0M0 no adverse features Breslow ≤ 1mm T1a no ulceration (U-) mitotic rate less than 1 mm 2

Stage IB: cT1bN0M0 OR cT2aN0M0

Stage IIA: T2bN0M0 and T3aN0M0

Stage IIB: cT3bN0M0 OR cT4aN0M0

Stage IIC cT4bN0M0

Stage IIIA: cT1a-T2a; N1a/N2a; M0

Stage IV T - any N - any M - 1

Case Example of Melanoma requiring parotidectomy (scroll to bottom of page): Parotidectomy with Facial Nerve Dissection; Posterolateral Neck Dissection

See Lecture "Melanoma Update" Dr. Hoffman to Iowa Derm Society April 2010 and updated 2011 with discussion re staging and margins: October 21 2011 Charleston South Carolina Head and Neck Oncology Lectureship

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Initial Evaluation

• History (Ward, Lambreton, Goel, et. al., 2017) 
  • Identify lesion characteristics, change(s), and associated symptoms like bleeding, crusting, and itching 
  • Identify history of sun exposure (excessive sunburns, tanning bed use, working outside, etc.) 
  • Personal and family history of skin cancer and cancer-prone syndromes (i.e. xeroderma pigmentosum) 
  • Discuss any history of excision of pre-malignant or malignant lesions 
  • Early identification of red-flag signs for metastatic disease (i.e. headache, seizure, vision changes, cough, shortness of breath, weight loss, fever, chills, etc.) 
• Physical Examination (Ward, Lambreton, Goel, et. al., 2017) 
  • Fitzpatrick skin type 
    • Type I (white skin, always burns) through Type VI (black skin, never burns). Patients with fair skin, closer to Type I, are at higher risk of developing melanoma. 
  • Identify lesions suspicious for melanoma 
    • ABCDEs of Melanoma: 
      • A: Asymmetry 
      • B: Irregular Borders 
      • C: Color – nevus with >1 color 
      • D: Diameter of lesion > 6 mm (pencil eraser) 
      • E: Evolution – nevus has gone through sudden changes in size/shape/color 
    • “Ugly duckling sign” –in an individual with multiple nevi, a nevus that is different from the rest in any of the above categories is considered suspicious (Grob and Bonerandi, 1998) 
    • Glasgow Seven Point Checklist – points given for major and minor criteria, lesions scoring 4 or more points warrant referral to a specialist for biopsy (Walter, 2013). 
      • Major (+2 points): change in size, irregular shape/border, and irregular color 
      • Minor (+1 point): largest diameter 7 mm or more, inflammation, oozing/crusting, and change in sensation (i.e. itching) 
    • Photograph the lesion 
  • Survey skin of head and neck; arrange dermatology consult for total body survey. 
  • Palpate neck for adenopathy

 

Diagnosis

• Biopsy; see: Melanoma Pathology Reporting Template
  • Document the location, extent, and character of the lesion with a photograph before biopsy 
  • Excisional biopsy and partial biopsy are appropriate, although excisional biopsy is preferred (Ward, Lambreton, Goel, et. al., 2017) 
    • Excisional biopsy margins (Pathak, 2023): 
      • 1-3 mm around the lesion (American Academy of Dermatology and National Comprehensive Cancer Network) 
      • 2 mm and upper subcutis (Cancer Council Australia) 
      • Minimal margins (European Society of Medical Oncology) 
    • Partial biopsy is typically completed via punch or shave technique 
      • Previously, shave biopsy was discouraged due to poor ability to assess Breslow depth. In a recent study of 600 patients, initial diagnosis with shave biopsy did not negatively impact disease free or overall survival (Ward, Lambreton, Goel, et. al., 2017) 
  • Histopathologic features depend on the subtype of melanoma, but asymmetry, ulceration, cellular atypia, involvement of the epidermis, lack of maturation, and atypical mitoses favor the diagnosis of malignant vs benign lesion (Filosa and Filosa, 2018) 
  • Important features in a report include (Swetter et al. 2021)(Filosa and Filosa, 2018): 
    • Breslow depth 
    • Margins 
    • Ulceration 
    • Increased mitotic rate 
    • Satellite lesions 
    • Invasion of local structures (lymphovascular invasion) 
    • Regression – signs that the host immune system has recognized and started to clear the primary tumor 
    • Perineural invasion 

 

Staging

Cutaneous malignant melanoma is staged using the American Joint Committee on Cancer (AJCC) 8th edition TNM staging system (Pathak, 2023) and includes assessment of the Tumor (T), Nodes (N), and Metastasis (M) 

• Tumor (T) category: based on the depth of invasion (Breslow depth) and the presence/absence of ulceration (based on histopathological, not gross, examination) 

 

Stage	Description
Tx	Tumor thickness cannot be assessed
T0	No evidence of primary tumor (unknown primary or regressed tumor)
Tis	Melanoma in-situ
T1	T1 Tumor <1 mm thick with unknown or unspecified ulceration        T1a Tumor <0.8 mm thick without ulceration        T1b Tumor 0.8 – 1 mm with/without ulceration OR Tumor < 0.8 mm with ulceration
T2	T2 Tumor > 1-2 mm thick with unknown or unspecified ulceration       T2a Tumor > 1-2 mm without ulceration       T2b Tumor > 1-2 mm with ulceration
T3	T3 Tumor > 2-4 mm thick with unknown or unspecified ulceration       T3a Tumor > 2-4 mm without ulceration       T3b Tumor > 2-4 mm with ulceration
T4	T4 Tumor > 4 mm thick with unknown or unspecified ulceration       T4a Tumor > 4 mm without ulceration       T4b Tumor > 4 mm with ulceration

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• Node (N) category identifies metastases to both regional lymph nodes and non-nodal regional sites 
  • Can be assessed clinically by assessing for lymphadenopathy on physical exam, radiographically using different imaging approaches, and sentinel lymph node biopsy 
    • Lymph nodes identified clinically or radiographically are referred to as “clinically apparent” 
    • Lymph nodes identified with sentinel lymph node biopsy are referred to as “clinically occult” 
  • Nodal metastases can also be described as in-transit, satellite, or microsatellite metastases 
    • Satellite – clinically evident cutaneous or subcutaneous metastatic disease occurring discontinuously within 2 cm of the primary tumor  
    • Micro-satellite – cutaneous or subcutaneous metastases occurring discontinuously within 2 cm of the primary tumor that can only be identified using microscopically 
    • In-transit – metastatic disease that is discontinuous and more than 2 cm from the primary tumor site  
  • Matted nodes – two or more lymph nodes that are connected together 

 

Stage	Description
Nx	Regional nodes not assessed, and no in-transit, satellite, or microsatellite metastases
N0	No metastases to regional nodes and no in-transit, satellite, or microsatellite metastases
N1	N1 One regional lymph node or any number of in-transit, satellite, or microsatellite metastases with no tumor involved regional node       N1a One clinically occult lymph node and no in-transit, satellite, or microsatellite metastases       N1b One clinically detected lymph node and no in-transit, satellite, or microsatellite metastases       N1c No regional lymph node and any number of  in-transit, satellite, or microsatellite metastases
N2	N2 Two or 3 tumors involved nodes or any number in-transit, satellite, or microsatellite metastases with one tumor involved node       N2a Two or 3 occult lymph nodes and no in-transit, satellite, or microsatellite metastases       N2b Two or 3, at least one clinically detected node and no in-transit, satellite, or microsatellite metastases       N2c One clinically occult or detected node and any number of in-transit, satellite, or microsatellite metastases
N3	N3 Four or more tumor involved nodes or any number of in-transit, satellite, or microsatellite metastases with two tumors involved node or any number of matted nodes with or without in-transit, satellite, or microsatellite metastases       N3a Four or more occult lymph nodes and no in-transit, satellite, or microsatellite metastases       N3b Four or more, at least one clinically detected node and no in-transit, satellite, or microsatellite metastases       N3c Two or more clinically detected and any number of in-transit, satellite, or microsatellite metastases or presence of matted nodes and any number of in-transit, satellite, or microsatellite metastases

 

• Metastasis (M) category – signifies distant metastases. Lactate dehydrogenase is used for additional subdivision 

 

Stage	Description
M0	No distant metastases
M1a	M1a Distant metastases to the skin, soft tissue, including muscle and non-regional lymph node       M1a LDH not available       M1a (0) LDH not elevated       M1a (1) LDH elevated
M1b	M1b Distant metastases to the lung with or without M1 site involvement       M1b LDH not available       M1b (0) LDH not elevated       M1b (1) LDH elevated
M1c	M1c Distant metastases to non-CNS sites with or without M1 or M2 sites       M1c LDH not available       M1c (0) LDH not elevated       M1c (1) LDH elevated
M1d	M1d Distant metastases to CNS sites with or without M1a, M1b, or M1c sites of involvement       M1d LDH not available       M1d (0) LDH not elevated       M1d (1) LDH elevated

 

Modifications from AJCC 7th Edition

(Gershenwald et al, 2017)

• Definition of Primary Tumor (T) 
  • All principal T-category tumor thickness ranges are maintained, but T1 now is subcategorized by tumor thickness strata at 0.8 mm threshold. 
  • Tumor mitotic rate was removed as a staging criterion for T1 tumors, but remains an overall important prognostic factor that should continue to be recorded for all patients with T1-T4 primary cutaneous melanoma. 
    • T1a melanomas now are defined as nonulcerated and <0.8 mm in thickness. 
    • T1b melanomas now are defined as 0.8 to 1.0 mm in thickness regardless of ulceration status or ulcerated melanomas <0.8 mm in thickness. 
    • T0 should be used if there is no evidence of a primary tumor (e.g. in a patient who presents with axillary metastasis and no known primary tumor). Staging may be based on clinical suspicious of a primary cutaneous melanoma, with the tumor categorized as T0. (Tis, not T0, designates melanoma in situ). 
    • Tumor thickness measurements now are recorded to the nearest 0.1 mm, not the nearest 0.01 mm, because of the impracticality and imprecision of measurements 
    • Tis (melanoma in situ), T0 (no evidence of a primary tumor), and TX (tumor thickness cannot be determined) may now be used as the T category designation for stage groupings. 
• Definition of Regional Lymph Node (N) 
  • Number of tumor-involved regional lymph nodes is maintained. 
  • Previously empirically defined "microscopic" and "macroscopic" descriptors are redefined as "clinically occult" (i.e. clinical Stage I-II with nodal metastasis determined at sentinel node biopsy) and "clinically detected" regional node disease (clinical Stage III), respectively. 
  • Sentinel node tumor burden is considered a regional disease prognostic factor that should be collected for all patients with positive sentinel nodes, but it is not used to determine N-category groupings. 
  • Non-nodal regional disease (i.e., microsatellites, satellites, and in-transit cutaneous and/or subcutaneous metastases) is more formally stratified by N category according to the number of tumor-involved lymph nodes. 
    • Presence of microsatellites, satellites, or in-transit metastases is now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any. 
  • "Gross" extranodal extension no longer is used as an N-category criterion (but the presence of "matted nodes" is retained). 
• Definition of Distant Metastasis (M) 
  • M1 is now defined by both anatomic site of distant metastatic disease and serum lactate dehydrogenase (LDH) value for all anatomic site subcategories. 
  • Descriptions of distant anatomic sites of disease are clarified in M subcategories. 
  • Descriptors were added to the M1 subcategory designation that provide LDH status for all sites of distant disease. 
  • New M1d designation was added to include distant metastasis to the central nervous system (CNS) with or without any other distant sites of disease; M1c no longer includes CNS metastasis. 
  • Elevated LDH level no longer define M1c 
• AJCC Prognostic Stage Groups 
  • No overall changes were made in the T subcategories, but definitions of T1a and T1b were refined. In addition, while the stage group for cT1bN0 remains clinical Stage IB, the stage group for pT1bN0 now is pathological Stage IA. 
  • N category now comprises four stage groups rather than three, and these groups are based on multivariable models, including T-category elements (tumor thickness and ulceration) and N-category elements (number of tumor-involved nodes, satellites/in-transits/microsatellites), demonstrating a significant impact of primary tumor factors in assigning N stage groups. 
  • Clarification is provided that Stage IV is not further stage grouped (i.e., M1c is Stage IV not Stage IVc). 

 

Pathological Prognostic Grouping

(Parthak, 2023)

Stage	Includes
Stage IA	T1a/T1b, N0, M0
Stage IB	T2a, N0, M0
Stage IIA	T2b/T3a, N0, M0
Stage IIB	T3b/T4a, N0, M0
Stage IIC	T4b, N0, M0
Stage IIIA	T1a/T1b/T2, N1a/N2b, M0
Stage IIIB	T1a/T1b/T2a/T2b/T3a, N1b/N1c/N2b, M0
Stage IIIC	T1a-T4b, N1a-N2c, M0
Stage IIID	T4b, N3a/N3b/N3c, M0
Stage IV	Any T, Any N, M1

 

Clinical Prognostic Grouping 

(Parthak, 2023)

Stage	Includes
Stage 0	Tis, N0, M0
Stage IA	T1a, N0, M0
Stage IB	T1b/T2a, N0, M0
Stage IIA	T2b/T3a, N0, M0
Stage IIB	T3b/T4a, N0, M0
Stage IIC	T4b, N0, M0
Stage III	Any T, N1/N2/N3, M0
Stage IV	Any T, Any N, M1

 

Treatment Considerations

• Excision 
  • Primary treatment of cutaneous malignant melanoma is resection with wide, circumferential margins largely influenced by Breslow depth 
    • Melanoma in situ: 5 mm 
    • 1 – 2 mm: 1 cm 
    • 2 – 4 mm: 2 cm 
    • > 4 mm: > 2 cm 
  • Margins are not inviolate and may be modified by proximity to critical structures with attention to lymphatic drainage patterns 
  • Moh’s microsurgery is not routinely recommended as first-line surgical management. It is more appropriate to consider Moh’s in the setting of cutaneous melanoma of the face or acral structures of lentigo maligna (Pathak, 2023) 
• Labs (Pathak, 2023) 
  • American Academy of Dermatology (AAD): no baseline labs for patients with clinical stage 0-II melanoma 
  • National Comprehensive Cancer Network (NCCN): no baseline labs for patients with clinical stage 0-IIIB melanoma 
  • All guidelines (AAD, ESMO, NCCN, CCA) recommend serum LDH in metastatic disease for prognostication 
• Imaging (Pathak, 2023) 
  • Guidelines differ by organization 
    • European Society of Medical Oncology (ESMO): PET and MRI brain for patients with stage III disease (or higher) OR tumor pT3b (or higher) 
    • National Comprehensive Cancer Network (NCCN): PET and MRI brain for patient with stage III disease or higher. Consider PET and MRI brain for patients with 
      • Early stage disease and with signs/symptoms of metastatic spread 
      • Positive sentinel lymph node biopsy 
      • Microscopic satellite or in-transit metastatic lesions 
      • Clinically palpable lymphadenopathy 
    • Cancer Council Australia (CCA): no additional imaging for patients with positive sentinel lymph node biopsy. Recommend PET and MRI brain in patients with clinically palpable lymphadenopathy 
• Sentinel lymph node biopsy 
  • Recommended for patients with tumor thickness greater than 0.8 mm (Parthak, 2023) 
  • Evaluation of a positive sentinel lymph node biopsy is with regional nodal ultrasound (preferred to complete lymph node dissection) 
    • MSLT-II and DeCOG-SLT trials showed no improvement in overall survival in patients treated with lymph node dissection vs regional nodal ultrasound (Durham and Wong, 2014)(Morton et. al., 2014) 
• Complete lymph node dissection (Falk Delgado, 2019) 
  • Rationale: to inhibit the systemic spread of melanoma and obtaining accurate staging 
  • Was a cornerstone in the surgical management of melanoma; however, sentinel lymph node biopsy has largely replaced this technique 
  • In the case of a positive sentinel lymph node biopsy, it is important to explain the risks and benefits of surveillance alone vs complete lymph node dissection  
• Systemic therapy  
  • Cutaneous melanoma (Pathak, 2023) 
    • Recommended for  
      • Stage IIC disease with high-risk features such as ulceration 
        • Adjuvant interferon 
      • Stage III disease  
        • Anti-PDL-1 inhibitors 
        • BRAF/MEK inhibitors 
      • Stage IV disease 
        • Anti-PDL-1 inhibitors and BRAF/MEK inhibitors 
        • If patients show disease progression after being treated with one of the above agents, checkpoint inhibitors can be considered 
        • Metastatic CNS disease 
          • Asymptomatic, limited disease can be treated with systemic therapy first 
          • Symptomatic, bulky disease is typically treated first with stereotactic surgery followed by systemic therapy 
  • Recommended for desmoplastic melanoma after wide local excision and concerning features, such as tumor thickness > 4 mm, perineural invasion (PNI), primary tumor site being the head/neck, and narrow margins of resection 
• Genetic counseling (Pathak, 2023) 
  • AAD and NCCN recommend genetic counseling and testing for mutations in CKDNK2, CDK4, TERT, BAP-1, and others for 
    • History of cutaneous melanoma or pancreatic cancer in three or more relatives on the same side of the family 
    • Personal past medical history of multiple episodes of invasive cutaneous melanoma (with one being diagnosed before the age of 45) 
    • Family history of mesothelioma, meningioma, or uveal melanoma and one or more intradermal tumors with a BAP-1 mutation  
    • Two or more melanocytic atypical intradermal tumors with a BAP-1 mutation 
  • ESMO recommends BRAF testing after all excisional biopsies. Also recommends actionable mutation testing at the time of excisional biopsy for the following populations ((Michielin et al. 2019) 
    • Patients with stage III or stage IV disease 
    • High-risk resected stage IIC disease 
• Follow-up Care 
  • Modify significantly according to prognosis 
  • Avoidance of sun exposure  
  • Surveillance as per NCCN Guidelines (Coit et. al., 2010) 
    • All melanoma patients: Skin examination and surveillance at least once a year for life is recommended 
    • Stage IA to IIA: Comprehensive H&P with specific emphasis on the regional nodes and skin every 6-12 months for five years and annually thereafter. Routine lab or imaging not useful in this group. 
    • Stage IIB-IV melanoma, NED: Comprehensive H&P every 3-6 months for 2 years; then every 3-12 months for 3 years and annually thereafter. CXR, CT, MRI and/or PET/CT can be considered to screen for recurrent or metastatic disease at the discretion of the physician. Because most recurrences manifest within the first 3 years, routine imaging is not recommended beyond 3-5 years. 
  • Surveillance as per ESMO Guidelines (Michielin et al. 2019) 
    • No consensus on the optimal schedule for follow-up visits, imaging, or blood testing 
    • Generally recommend follow-up visits every 3 months during the first 3 years, and every 6-12 months thereafter 

 

Stage 0

Stage 0: TisN0M0 Melanoma in situ, lentigo maligna (8th Edition AJCC)

5-year overall survival rate = 99 to 100% (Gershenwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO) (Michielin et al, 2019)	0.5 cm	No	No	No	No	No	No
National Comprehensive Cancer Network (NCCN) (Swetter et al, 2021)(Vetto, 2024)	0.5 - 1 cm	Consider	No	No	No	No	No

Additional comments:

• ESMO: Consider radiation for lentigo maligna melanoma in rare cases when excision is not possible due to patient comorbidities or high morbidity of the excision itself. 

• NCCN: Guidelines have been updated to clarify that for melanoma in situ, lentigo maligna, and acral lentiginous melanoma, wider margins may be needed and techniques for comprehensive histologic margin assessment (Mohs) may be considered.  

 

Stage IA

Stage IA cT1aN0M0: T1a: Breslow <0.8 mm, no ulceration (U-)

Stage IA T1N0M0 no adverse features Breslow ≤ 1mm T1a no ulceration (U-) mitotic rate less than 1 mm 2

5-year survival = 99% (Gersehnwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO) (Michielin et al, 2019)	1 cm	No	No	No	No	No	No
National Comprehensive Cancer Network (NCCN) (Swetter et al, 2021)(Vetto, 2024)	1 cm	No	No	No	No	No	No

Additional comments:

• ESMO: Sentinel lymph node biopsy can be discussed in pT1a for special cases (e.g. ≥3 mitoses/mm², a positive deep margin or when Breslow thickness cannot be reliably determined) 

• NCCN: If there is clinical uncertainty about the microstaging or, in the rare event that a conventional high-risk feature is present (e.g., ulceration, high mitotic rate, lymphovascular invasion), SLNB can be discussed 

   

Stage IB

Stage IB: T1bN0M0, T2aN0M0

5-year survival = 97% (Gershenwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)(Michielin et al, 2019)	1 cm	No	Yes	No	No	No	No
National Comprehensive Cancer Network (NCCN)(Swetter et al, 2021)(Vetto, 2024)	1 - 2 cm	No	Yes	No	No	No	No

Additional comments:

• ESMO: SLNB is recommended for all patients with pT1b or higher disease. 

• NCCN: For patients with clinical stage IB, the probability of a positive SLNB is 5%-10% and NCCN recommends discussing and considering SLNB for these patients 

 

Stage IIA

Melanoma Stage IIA: T2bN0M0 and T3aN0M0

5-year survival = 94% (Gershenwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)(Michielin et al, 2019)	1 -2 cm	No	Yes	No	No	No	No
National Comprehensive Cancer Network (NCCN)(Swetter et al, 2021)(Vetto, 2024)	1 -2 cm	No	Yes	No	No	No	No

Additional comments

• NCCN: Consider nodal basin ultrasound prior to sentinel lymph node biopsy for melanoma patients with an equivocal regional lymph node physical exam. Nodal basin US is NOT a substitute for SLNB. 

 

Stage IIB

Stage IIB: T3bN0M0, T4aN0M0

5-year survival = 94% (Gershenwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)(Michielin et al, 2019)	2 cm	No	Yes	Yes	Yes	No	No
National Comprehensive Cancer Network (NCCN)(Swetter et al, 2021)(Vetto, 2024)	2 cm	No	Yes	No	No	No	No

Additional comments

• ESMO: PET/CT scan should be applied only for very high-risk patients, defined as pT3b and higher. 

• NCCN: Consider nodal basin ultrasound prior to sentinel lymph node biopsy for melanoma patients with an equivocal regional lymph node physical exam. Nodal basin US is NOT a substitute for SLNB. 

 

Stage IIC

Stage IIC: T4bN0M0

5-year survival = 82% (Gershenwald et al, 2017)

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	2 cm	No	Yes	Yes	Yes	No	No
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	2 cm	No	Yes	No	No	No	No

Additional comments

• NCCN: Consider nodal basin ultrasound prior to sentinel lymph node biopsy for melanoma patients with an equivocal regional lymph node physical exam. Nodal basin US is NOT a substitute for SLNB. BRIM8 trail showed that in select patients with resected AJCC 7th Edition stage IIC-III disease and BRAF V600 mutation, adjuvant treatment with the BRAF inhibitor, vemurafenib monotherapy improved disease-free survival (DFS) and possibly DMFS compared to placebo.  The impact on overall survival (OS) was not statistically significant. Vermuranfenib monotherapy was associated with higher rates of toxicity compared to placebo and is NOT FDA approved for adjuvant treatment of melanoma (Maio et. al., 2018) 

 

Stage IIIA

Stage IIIA: T1a-T2a; N1a/N2a; M0

5-year survival = 93% (Gershenwald et. al., 2017) 

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	2 cm	No	Yes	Yes	Yes	No	Consider
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	Per tumor(T) classification	No	Yes	Yes	Yes	Consider	Yes

Additional comments

• ESMO: There may be some subsets of stage IIIA patients with higher risk of relapse (tumor burden with sentinel node >1 mm).  In these patients, discussion of risk reduction and long-term side-effects of adjuvant therapy can be considered. 

• NCCN: If patient is sentinel node positive, consider imaging for baseline staging, nodal basin US surveillance (preferred) or completion lymph node dissection (CLND). Consider BRAF mutation testing. Adjuvant options include nivolumab, pembrolizumab, and dabrafebib/trametinib (BRAF-600 activating mutations) 

 

Stage IIIB

5-year survival = 83% (Gershenwald et. al., 2017) 

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	2 cm	No	Yes	Yes	Yes	No	Consider
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	Per tumor (T) classification	No	Yes	Yes	Yes	Consider	Yes

Additional comments

• ESMO: T-VEC is a local injection therapy for unresectable metastatic melanoma lesions that was approved based on results from a phase III trial (Harrington et. al., 2016) 

• NCCN: If patient is sentinel node positive, consider imaging for baseline staging, nodal basin US surveillance (preferred) or completion lymph node dissection (CLND). Consider BRAF mutation testing. Adjuvant options include nivolumab, pembrolizumab, and dabrafebib/trametinib (BRAF-600 activating mutations) 

​

Stage IIIC

5-year survival = 69% (Gershenwald et. al., 2017) 

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	2 cm	No	Yes	Yes	Yes	No	Consider
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	Per tumor (T) classification	No	Yes	Yes	Yes	Consider	Yes

Additional comments

• ESMO: T-VEC is a local injection therapy for unresectable metastatic melanoma lesions that was approved based on results from a phase III trial (Harrington et. al., 2016) 

• NCCN: If patient is sentinel node positive, consider imaging for baseline staging, nodal basin US surveillance (preferred) or completion lymph node dissection (CLND). Consider BRAF mutation testing. Adjuvant options include nivolumab, pembrolizumab, and dabrafebib/trametinib (BRAF-600 activating mutations) 

 

Stage IIID

5-year survival = 32% (Gershenwald et. al., 2017) 

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	2 cm	No	Yes	Yes	Yes	No	Consider
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	Per tumor (T) classification	No	Yes	Yes	Yes	Consider	Yes

Additional comments

• ESMO: T-VEC is a local injection therapy for unresectable metastatic melanoma lesions that was approved based on results from a phase III trial (Harrington et. al., 2016) 

• NCCN: If patient is sentinel node positive, consider imaging for baseline staging, nodal basin US surveillance (preferred) or completion lymph node dissection (CLND). Consider BRAF mutation testing. Adjuvant options include nivolumab, pembrolizumab, and dabrafebib/trametinib (BRAF-600 activating mutations) 

   

Stage IV

Stage IV: AnyT; AnyN; M1a-d

5-year survival = <10% (Gershenwald et. al., 2017) 

Guidelines	Margins	Mohs	SLN Biopsy	PET	CT	Radiation	Adjuvant
European Society of Medical Oncology (ESMO)  (Michielin et al. 2019)	No need to resect	No	Yes	Yes	Yes	No	Consider
National Comprehensive Cancer Network (NCCN)  (Swetter et al. 2021)(Vetto, 2024)	Per tumor (T) classification	No	Yes	Yes	Yes	Yes	Yes

Additional comments

• ESMO: T-VEC is a local injection therapy for unresectable metastatic melanoma lesions that was approved based on results from a phase III trial (Harrington et. al., 2016) 

• NCCN: If patient is sentinel node positive, consider imaging for baseline staging, nodal basin US surveillance (preferred) or completion lymph node dissection (CLND). Consider BRAF mutation testing. Adjuvant options include nivolumab, pembrolizumab, and dabrafebib/trametinib (BRAF-600 activating mutations) 

 

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References

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