Current Staging and Prognostic Factors in Melanoma

The current American Joint Commission for Cancer staging system for melanoma includes thickness, ulceration, and mitotic index as primary tumor factors for patients with stage I and II disease. Number and size of nodal metastases, presence of satellitosis and in-transit disease, and tumor ulceration status categorize patients with stage III disease. Presence and location of distant metastatic disease and increased lactate dehydrogenase level stratify prognosis in patients with stage IV disease. Factors predictive of sentinel lymph node positivity are also studied, particularly in patients with T1 melanomas, but are not always congruent with those predictive of survival.

Key points

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In the current (seventh) edition of the American Joint Commission for Cancer staging system, tumor thickness, ulceration status, and mitotic index categorize patients with stage I and II melanoma.
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Size (micro vs macro), number of nodal metastases, presence of satellitosis or in-transit disease, and primary tumor ulceration status categorize patients with stage III disease.
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For stage IV disease, location of distant metastases (skin/subcutaneous/nodal vs lung vs nonlung visceral) and increased lactate dehydrogenase levels categorize patients with M1 status.
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Other pathologic and clinical factors of the primary tumor have been reported with variable prognostic significance: presence of tumor-infiltrating lymphocytes, absence of regression, younger age, female gender, and extremity location have generally been associated with more favorable outcomes.
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Prognostic factors for sentinel lymph node positivity overlap but are not uniformly congruent with those for survival.

Introduction

The current (seventh) edition of the American Joint Commission on Cancer (AJCC) staging system for melanoma is now approaching its sixth year since publication and is based on 30,946 patients with stage I, II, and III melanoma and 7972 patients with stage IV melanoma from 17 major medical centers or independent cancer centers. This article reviews the notable changes in the current staging system compared with the last and discusses this in the context of clinical management of patients. Tumor and patient factors are discussed that do not feature in the staging system but that nonetheless carry important prognostic significance.

Introduction

The current (seventh) edition of the American Joint Commission on Cancer (AJCC) staging system for melanoma is now approaching its sixth year since publication and is based on 30,946 patients with stage I, II, and III melanoma and 7972 patients with stage IV melanoma from 17 major medical centers or independent cancer centers. This article reviews the notable changes in the current staging system compared with the last and discusses this in the context of clinical management of patients. Tumor and patient factors are discussed that do not feature in the staging system but that nonetheless carry important prognostic significance.

Melanoma staging system

The current AJCC staging system for melanoma is shown in Tables 1 and 2 .

Table 1

Seventh edition of the AJCC TNM (tumor, node, metastasis) staging categories for melanoma

T Classification	Thickness (mm)	Additional Stratification
Tis	NA	NA
T1	≤1.00	a: Without ulceration and mitoses <1/mm2
T1	≤1.00	b: With ulceration or mitoses ≥1/mm2
T2	1.01–2.00	a: Without ulceration
T2	1.01–2.00	b: With ulceration
T3	2.01–4.00	a: Without ulceration
T3	2.01–4.00	b: With ulceration
T4	>4.00	a: Without ulceration
T4	>4.00	b: With ulceration
N Classification	Number of Metastatic Nodes	Metastatic Burden
N0	0	NA
N1	1	a: Micrometastasis (identified on SLN biopsy)
N1	1	b: Macrometastasis (identified on clinical examination)
N2	2–3	a: Micrometastasis (identified on SLN biopsy)
		b: Macrometastasis (identified on clinical examination)
		c: In-transit metastases/satellites without nodal metastases
N3	4+ metastatic nodes, matted nodes, or in-transit metastases/satellites with nodal metastases	—
M Classification	Site	Serum LDH Level
M0	No distant metastases	NA
M1a	Distant skin, subcutaneous, or nodal metastasis	Normal
M1b	Lung metastases	Normal
M1c	All other visceral metastases	Normal
M1c	Any distant metastasis	Increased

Abbreviations: LDH, lactate dehydrogenase; NA, not available; SLN, sentinel lymph node.

From Edge SB, Byrd DR, Compton CC, editors. AJCC Cancer Staging Manual. 7th edition. New York (NY): Springer, 2010; with permission.

Table 2

Seventh edition of the AJCC stage groupings for melanoma

Clinical Staging	T	N	M
0	Tis	N0	M0
IA	T1a	N0	M0
IB	T1b	N0	M0
IB	T2a	N0	M0
IIA	T2b	N0	M0
IIA	T3a	N0	M0
IIB	T3b	N0	M0
IIB	T4a	N0	M0
IIC	T4b	N0	M0
III	Any T	N > N0	M0
IV	Any T	Any N	M1
Pathologic Staging
0	Tis	N0	M0
IA	T1a	N0	M0
IB	T1b	N0	M0
IB	T2a	N0	M0
IIA	T2b	N0	M0
IIA	T3a	N0	M0
IIB	T3b	N0	M0
IIB	T4a	N0	M0
IIC	T4b	N0	M0
IIIA	T1–4a	N1a	M0
IIIA	T1–4a	N2a	M0
IIIB	T1–4b	N1a	M0
	T1–4b	N2a	M0
	T1–4a	N1b	M0
	T1–4a	N2b	M0
	T1–4a	N2c	M0
IIIC	T1–4b	N1b	M0
	T1–4b	N2b	M0
	T1–4b	N2c	M0
	Any T	N3	M0
IV	Any T	Any N	M1