M0 No detectable evidence of distant metastases
M1a Metastases to the skin, subcutaneous, or distant lymph nodes M1b Metastases to the lung
M1c Metastases to all other visceral sites or distant metastases to any site combined
with an elevated serum LDH
Note: Serum LDH is incorporated into the M category as shown below:
aMicrometastases are diagnosed after sentinel lymph node biopsy and completion of lymphadenectomy (if performed).
bMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.
Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Seventh Edition (2010), published by Springer Science+Business Media. Any citation or quotation of this material must be credited to the AJCC as its primary source. The inclusion of this information herein does not authorize any reuse or further distribution without the expressed, written permission of Springer, on behalf of the AJCC.
VII. METASTATIC AND RECURRENT MELANOMA
A. Local recurrence is related to tumor thickness and defined as a recurrence in close proximity to the surgical scar or site of primary cutaneous melanoma (3% rate).
B. In-transit metastases/satellites are small cutaneous tumors present in the dermis and subdermal between the primary melanoma site and the draining nodal basin.
C. Lesions occurring within 2 cm of primary tumor are termed satellites, whereas in-transit metastases are more than 2 cm from site.
D. Regional lymph node metastasis
1. Highly predictive of visceral metastases
2. Risk varies based on tumor thickness of primary
E. Distant metastasis is most frequently to nonvisceral sites, skin, subcutaneous tissue, and distant lymph nodes.
F. Late recurrences occur 10 or more years after initial diagnosis and treatment.
VIII. THERAPEUTIC MODALITIES BY STAGE
A. Stage 0 (Melanoma in situ) Complete excision with safety margins: wide local excision surgery (WLE) with appropriate benign margins (depends on the size and thickness of the
tumor)
1. Melanoma in situ: 0.5-cm normal skin safety margin
2. Melanoma tumor less than 1 mm: 1-cm horizontal and vertical margin
3. Melanoma tumor greater than 1 mm: 2- to 3-cm resection margin decided by the anatomical location and conditions
B. Stage I Treatment
1. SLNB is recommended by AJCC for ulcerated lesion thicker than 1 mm in order to determine the involvement of local lymph nodes and guidance of treatment options.
2. Free of lymph node involvement leads to WLE surgery with appropriate benign margins (depends on the size and thickness of the tumor).
C. Stage II Treatment
1. SLNB is recommended before undergoing surgery for determining the involvement of local lymph nodes and guides treatment options.
a. Sentinel lymph node dissection: use blue dye or radiolabeled colloid injection at the melanoma site and open the close-by lymph node basin to check the presence of melanoma. Free of tumor at the closest lymph node from the primary tumor site suggests negative for metastasis.
2. WLE surgery with appropriate margins (depends on the size and thickness of the tumor).
3. Adjuvant therapy is considered for stage IB and stage IIC melanoma (e.g., interferon alfa- 2a and interferon alfa-2b), which helps immune system fight the disease and delay or prevent recurrence.
4. Some clinical trials used vaccine therapy for patients who could not tolerate interferons;
no significant increase in survival rate was shown in randomized controlled trials.
D. Stage III Treatment
1. WLE removal of the primary lesion is recommended for recurrent tumors and in-transit tumors.
2. Therapeutic lymph node dissection (TLND) of the melanoma affected regional lymph nodes for the patient with palpable lymph nodes for possible macrometastases.
3. Selected patients will have lymphatic mapping and SLND for determining involvement of sentinel node.
4. Systemic adjuvant therapy in addition to the surgery with interferons (alfa-2a and alfa- 2b), which helps immune system to fight the disease and delay or prevent recurrence.
5. Radiation adjuvant therapy: may consider use of radiation therapy when the tumor has involved tissues beyond lymph nodes to control further spread of melanoma.
a. Regional metastasis radiation therapy (in-transit metastasis).
b. Adjuvant therapy recommended for postsurgical melanoma patients who are free of disease but at high risk for relapse and to complement surgery in the management of melanoma metastatic to lymph nodes.
c. Stereotactic radiation therapy is considered for brain metastases up to two sites;
otherwise, radiation of the entire brain for more than two metastatic tumors.
d. Palliative radiotherapy for bone metastases.
E. Stage IV Treatment
1. Surgical removal of metastatic tumors for symptoms treatment
2. Systemic adjuvant therapyChemotherapy 3. Dacarbazine (DTIC) IV infusion
4. Temozolomide oral medication for advanced metastatic melanoma
5. IL-2 or IFNa (biochemotherapy) alone or combination treatment with dacarbazine, cisplatin, temozolomide, carmustine, vinblastine, and tamoxifen.
6. Immunotherapies (e.g., IL-2, INF-α2a and ipilimumab): Treatment strategies with vaccines utilizing tumor cells, antibodies, peptides, and dendritic cells.
7. Specific target therapies: Vemurafenib treatment for BRAF mutation genetic signaling pathways in metastatic and unresectable (inoperable) melanoma.
8. Radiation therapy including x-rays and gamma rays targeting cancer cells, and relieve symptoms to control pain in metastatic disease involving the brain
IX. PROGNOSIS
A. Follow-Up Recommendations
1. Follow-up one to four times per year, for 2 years, depending on the thickness of the primary lesion and other risk factors, then one to two times per year thereafter.
2. Post melanoma treatment follow up should be tailored to each patient’s history of type and thickness of melanoma, presence of atypical nevi, family history of melanoma, patient anxiety, and patient ability to recognize signs and symptoms of disease.
3. Strong evidence suggests that the majority of metastases and recurrences are discovered by the patient or a family member. Therefore, the patient education program should include how to perform self-conducted skin examination.
4. 5-year and 10-year survival rate: the 5-year survival rate with stages I and II is over 90%, whereas with stage IV, it is approximately 10% to 20%.