SkinCancerNet Article
Melanoma:  How It is Staged and Treated

Stage indicates how far the cancer has spread. Knowing the stage of the cancer allows the dermatologist, or team of cancer specialists, to plan appropriate treatment.

Stage 0 | Stage 1A | Stage IB | Stage II | Stage III | Stage IV | Follow Up | Recurrence

The Staging Process
The stage may be determined during the biopsy performed to learn if skin cancer is present. Most early melanomas can be staged this way, and additional testing is not needed. Surgical removal of the melanoma and a margin of normal-looking skin is typically all that is required to treat early-stage melanoma. This surgery may be performed in a dermatologist’s office under local anesthesia. The cure rate averages 95%.

Additional medical testing is required to stage the melanoma when there is a possibility that the cancer may have spread. Sometimes surgery is necessary to stage the melanoma.

About the Information Presented Below
The following provides general information about staging and treating melanoma. A patient’s doctor may recommend a treatment option not mentioned below. Circumstances unique to each person ultimately determine how the melanoma is treated. For example, on occasion, melanoma in situ (stage 0) is treated with radiation therapy. Since radiation therapy is not used to treat a large number of people diagnosed with melanoma in situ, it is not listed below.

Stage 0
Description of the stage – Also called melanoma in situ. In this stage, the cancer is confined to the outermost layers of skin (epidermis).

Additional testing before treatment – None.

Treatment – Surgical removal of any remaining tumor and a margin of normal-looking skin.

While the tumor may have been completely removed when tissue was taken for the biopsy, treatment requires a margin of normal-looking skin to be removed from around the melanoma site. This skin is examined under a microscope to verify that it does not contain cancer cells. The cure rate in stage 0 ranges from 99.5% to 100%.

Adjuvant therapy – Usually none.

Stage IA
Description of the stage – The tumor has grown beyond the outermost layers of skin (epidermis) and reached the middle layers of the skin (dermis). The thickness of the tumor measures 1 millimeter or less. The surface of the skin covering the tumor is intact (without ulceration), and the cancer has not spread to the lymph nodes or a distant site.

Additional testing before treatment – The risk of melanoma spreading to the lymph nodes is low; however, a sentinel lymph node biopsy (SLNB) may be recommended when a tumor measures .75 to 1.0 millimeters.

A SNLB is a surgical procedure used to determine if cancer has spread to the sentinel lymph node — the first lymph node to receive lymph draining from the site of the primary tumor. After the surgeon identifies the sentinel lymph node, it is removed and sliced into sections for laboratory analysis to determine if cancer cells are present. A SLNB is performed during the same surgical session as the surgical removal of any remaining tumor and a margin of normal-looking skin.

When cancer is detected in the sentinel lymph node, the melanoma has reached stage III or stage IV. The melanoma is no longer classified as stage IA, and additional testing is conducted to determine if the melanoma is in stage III or stage IV. Treatment is guided by the corresponding stage.

If cancer is not found in the lymph node, it is unlikely the cancer has spread, and the node is said to be negative. This confirms that the melanoma is in stage IA.

Treatment – Surgical removal of any remaining tumor and a margin of normal-looking skin. The normal-looking skin is examined under a microscope to verify that cancer cells are not present.

Adjuvant therapy – Usually none.

Stage IB
Description of the stage – Melanoma in this stage fits one of the following descriptions:

• The tumor measures less than 1 millimeter and:

  • The top layer of skin that covers the tumor is not intact (ulcerated).

or

• The tumor has penetrated to the lower dermis or the subcutis.

• The tumor measures from 1.01 to 2.0 millimeters, and the top layer of skin covering the tumor is intact (without ulceration).

In stage IB, there is no evidence that the cancer has spread to the lymph nodes or a distant site.

Additional testing before treatment – Depending on the patient’s signs and symptoms, one or more of the following tests may be ordered:

• Blood test to check LDH level

• Chest x-ray

Lymph node evaluation – When the melanoma progresses beyond stage 1A, a sentinel lymph node biopsy (SLNB) may be recommended. A SNLB is a surgical procedure used to determine if cancer has spread to the sentinel lymph node — the first lymph node to receive lymph draining from the site of the primary tumor. After the surgeon identifies the sentinel lymph node, it is removed and sliced into sections for laboratory analysis to determine if cancer cells are present. A SLNB is performed during the same surgical session as the surgical removal of any remaining tumor and a margin of normal-looking skin.

When cancer is detected in the sentinel lymph node, the melanoma has reached stage III or stage IV. The melanoma is no longer classified as stage IB, and additional testing is conducted to determine if the melanoma is in stage III or stage IV. Treatment is guided by the corresponding stage.

If cancer is not found in the lymph node, it is unlikely the cancer has spread, and the node is said to be negative. This confirms that the melanoma is in stage IB.

Treatment – In stage 1B, treatment consists of:

• Surgical removal of any remaining tumor and a margin of normal-looking skin (surgical excision). The normal-looking skin is examined under a microscope to verify that cancer cells are not present.

• Clinical trial – Some patients with stage IB melanoma participate in clinical trials that evaluate new techniques for detecting the spread of melanoma to the sentinel lymph node.
  
  A clinical trial may be recommended when it is believed the treatment being studied can benefit the patient. If this is a consideration, the patient should discuss the potential risks and benefits with a doctor who is treating the patient for melanoma. The decision of whether or not to enroll in a clinical trial rests entirely with the patient.

Adjuvant Therapy – Usually none. When adjuvant therapy is recommended for stage 1B, it typical involves participating in a clinical trial that is evaluating potential therapies for preventing spread or recurrence. Adjuvant therapy may involve additional surgery to the lymph nodes nearest the melanoma, immunotherapy, chemotherapy, or a combination of these treatments.

Stage II
Description of the stage – A melanoma is classified as stage II when the tumor fits one of the following descriptions, and there is no evidence that the cancer has spread to the lymph nodes or a distant site:

As the above table indicates, the letter following the number indicates the severity of the melanoma, with A being less severe than C.

Additional testing before treatment – Depending on the patient’s signs and symptoms, one or more of the following tests may be recommended:

• Blood test to check LDH level

• Imaging tests, such as chest x-ray, CT scan, MRI, PET scan

Lymph node evaluation – Melanoma has the potential to spread. Most often, it spreads to the closest lymph nodes first. If the melanoma is in stage II, the patient may be asked to consider the option of having a sentinel lymph node biopsy (SLNB), a surgical procedure that is performed to determine if the cancer has spread to the lymph node(s). The sentinel lymph node is the first lymph node to receive lymph draining from the site of the primary tumor. After the surgeon identifies the sentinel lymph node, it is removed and sliced into sections for laboratory analysis to determine if cancer cells are present. Sometimes two or three nodes are removed for analysis. This procedure is performed during the same surgical session as the surgery to remove any remaining tumor and a margin of normal-looking skin.

When cancer is detected in the sentinel lymph node, the melanoma has reached stage III or stage IV. The melanoma is no longer classified as stage II, and additional testing is conducted to determine if the melanoma is in stage III or stage IV. Treatment is guided by the corresponding stage.

If cancer is not found in the lymph node, it is unlikely the cancer has spread, and the node is said to be negative. This confirms that the melanoma is in stage II.

Treatment – Surgical removal of any remaining tumor and a margin of normal-looking skin is the primary treatment for stage II melanoma. The normal-looking skin is examined under a microscope to verify that cancer cells are not present. As indicated above, a sentinel lymph node biopsy also may be performed to determine if the cancer has spread.

Adjuvant Therapy – In stage II, the risk of melanoma cells breaking away from the primary tumor and spreading increases. When the melanoma measures more than 4.0 millimeters or reaches stage IIC, high-dose interferon injections may be recommended. The purpose of adjuvant therapy in stage II is to destroy melanoma cells that cannot be detected and to prevent recurrence. Adjuvant therapy for stage II is administered in a clinical trial and may involve:

• High-dose interferon injections. Clinical trials continue to investigate the use of high-dose interferon injections and the effect on relapse-free and overall survival. Some trials have shown a statistically significant increase in relapse-free and overall survival when patients receive high-dose interferon. As these injections can help boost the patient’s immune system, this is a type of immunotherapy. Interferons are naturally produced by the body’s immune system. However, as a medication, interferon can produce undesirable side effects, including aches, chills, fever, and extreme fatigue. Interferon also can affect the heart and liver, so it should only be administered by a physician who is experienced in using this treatment to minimize side effects and increase effectiveness.
   

• Other types of immunotherapy. Immunotherapy can help a patient’s immune system destroy cancer cells. Interferon (described above) is only one type of immunotherapy being explored in clinical trials. Today, about 75% of clinical trials for melanoma are investigating some form of immunotherapy.
   

• Chemotherapy. Using medication to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing, is being investigated in clinical trials for stage II melanoma.
   

• New techniques for detecting spread to the lymph nodes.

A clinical trial may be recommended when it is believed the treatment being studied can benefit the patient. If this is a consideration, the patient should discuss the potential risks and benefits with a doctor who is treating the patient for melanoma. The decision of whether or not to enroll in a clinical trial rests entirely with the patient.

Stage III
Description of the stage – In stage III, the melanoma has spread to one or more lymph node, and the thickness of the tumor is no longer the most important factor. Stage III is divided into IIIA, IIIB, and IIIC. The letter following the number indicates the severity, with A being less severe than C. In Stage III, there is no evidence that the melanoma has spread to a distant site.

Additional testing before treatment – When cancer is found in a lymph node, the following tests are routinely ordered:

• Blood test to check LDH levels

• Chest x-ray

Depending upon the patient’s symptoms, one of the following also may be ordered:

• Imaging tests, such as CT scan, MRI, or PET scan

Additionally, a second biopsy may be performed before treatment. Unlike the first biopsy in which the melanoma tumor or a portion of it was removed, this biopsy takes a sample from a lymph node that feels hard or enlarged or another melanoma nodule if the patient has developed more than one nodule. One of the following biopsies may be performed:

• Fine needle aspiration biopsy (FNA)

• Open biopsy

If testing finds that the melanoma has spread beyond the lymph nodes, the melanoma is classified as stage IV, not stage III, and guidelines for stage IV are followed.

Treatment – The primary treatment for stage III melanoma is surgical removal of the melanoma and a margin of normal-looking skin from around each tumor along with surgical removal of the lymph nodes (lymphadenectomy) in the area(s) where melanoma is found.

In stage III, surgical removal of the melanoma is not always feasible, and one or more of the following forms of treatment may be considered:

• Clinical trial - In stage III, the patient usually receives chemotherapy, medication used to kill cancer cells or stop them from dividing, through a clinical trial. If the tumor is located on an arm or leg, a modified form of chemotherapy, isolated limb perfusion, may be used. Isolated limb perfusion involves temporarily stopping the flow of blood to the affected limb with a tourniquet and administering a high dose of chemotherapeutic medication, such as melphalan, to the area. It is believed that high doses can more effectively destroy the cancerous cells and cause less damage to healthy tissue. This has been beneficial for some patients.
  
  Sometimes an investigational therapy, such as combining chemotherapy with immunotherapy, may be recommended. This has helped some patients. About 75% of the clinical trials for melanoma are investigating immunotherapies.
  
  A clinical trial may be recommended when it is believed the treatment being studied can benefit the patient. If this is a consideration, the patient should discuss the potential risks and benefits with a doctor who is treating the patient for melanoma. The decision of whether or not to enroll in a clinical trial rests entirely with the patient.
   

• Immunotherapy - If several melanoma lesions have developed and it is not possible to surgically remove each lesion and a margin of normal-looking skin from around each lesion, injections of BCG or interferon may be given. Both medications are approved for the treatment of melanoma. Some melanomas dissolve with such injections.
   

• Radiation therapy - When a patient undergoes radiation therapy, high-energy rays are directed to the area(s) of the body affected by the melanoma in order to kill malignant cells. This form of therapy is not used to treat a single melanoma lesion.

Adjuvant therapy – In Stage III, adjuvant therapy is usually recommended when there is no evidence of melanoma after treatment. Several types of adjuvant therapy are used in Stage III. Immunotherapy with high dose interferon is most commonly administered. Several new therapies are being investigated in clinical trials, including chemoimmunotherapy (combining chemotherapy and immunotherapy) and immunotherapy. Chemotherapy and radiation therapy also may be used. These are similar to the therapies used when surgical removal of the tumor is not feasible, and are described above under treatment for stage III melanoma.

Stage IV
Description of the stage – When melanoma is diagnosed as stage IV, the cancer has spread to a distant site. In stage IV, the original melanoma tumor may be any thickness.

Additional testing before treatment – When there is evidence that the melanoma has spread beyond the lymph nodes nearest the original tumor, the first step is to confirm that the melanoma has metastasized (spread), and a biopsy is performed. The type of biopsy used will depend on where the cancer is believed to have spread. A fine needle aspiration biopsy (FNA) or open biopsy may be appropriate. Other tests will be conducted to determine the extent of the cancer spread and may include:

• Chest x-ray

• Blood test to check LDH levels

• CT scan of the chest or abdomen and pelvis, or all three areas

• Other imaging tests, such as MRI or PET scan

Treatment – Treatment depends on several factors, including the patient’s condition and whether the cancer has spread to one area or multiple areas of the body.

When the melanoma spreads to one area – The primary treatment for melanoma that spreads to one site is surgical removal of the melanoma. In some cases, surgical removal may not be feasible or may not be able to remove all of the cancer. In these cases, stage IV melanoma that has spread to one area may be treated with:

• Chemotherapy - Chemotherapy is the use of cancer-fighting medications to stop the growth of malignant cells. In stage IV melanoma, systemic (affects the entire body) chemotherapy is used. One medication that may be used is dacarbazine (DTIC), which is approved by the U.S. Food and Drug Administration (FDA) for treating melanoma. DTIC is given intravenously for 1 to 10 days. The dosing schedule depends on the patient’s condition and ability to tolerate side effects, which may include nausea, vomiting, pain at the injection site, and fatigue. DTIC often is used in combination with another cancer medication(s) as research shows this can increase effectiveness. Another chemotherapeutic medication used to treat stage IV melanoma is temozolomide, which may be administered alone or with another medication.
   

• Close observation - This option involves delaying treatment for up to three months and repeating scans and other medical tests to see if the melanoma continues to spread. If the melanoma does not spread and it is believed that surgery will remove the melanoma, surgery is performed. Sometimes surgery cures the cancer.
   

• Immunotherapy - Immunotherapy uses medication to stimulate or enhance the patient’s immune responses in order to fight established cancer. In stage IV, the systemic medication, interluekin-2 (IL-2), may be used.
   

• Palliative care - The purpose of this type of therapy is to relieve symptoms and improve a patient’s quality of life, not treat the cancer. Patients in all stages may receive palliative care. In advanced stages, palliative care can help control the symptoms and pain. Radiation therapy is a type of palliative care used in stage IV melanoma to relieve symptoms and ease pain.

Adjuvant therapy – After surgery, one of the following adjuvant therapies is usually recommended if it appears that the cancer has been removed:

• Clinical trial - A clinical trial may be recommended when it is believed the treatment being studied can benefit the patient. If this is a consideration, the patient should discuss the potential risks and benefits with a doctor who is treating the patient for melanoma. The decision of whether or not to enroll in a clinical trial rests completely with the patient.
   

• Close observation - The patient does not undergo further treatment but returns for frequent physical examinations and/or diagnostic tests that can detect cancer.
   

• Interferon injections - To help boost the patient’s immune system, injections of interferon-alpha may be given. Interferons are naturally produced by the body’s immune system. However, as a medication, interferon-alpha can produce undesirable side effects, including aches, chills, fever, and extreme fatigue. Interferon-alpha also can affect the heart and liver, so it should only be administered by a physician who is experienced in using this treatment to minimize side effects and increase effectiveness.

If all of the cancer cannot be removed, then systemic (affects the entire body) treatment with chemotherapy (cancer-fighting medications) or immunotherapy (medication used to boost the patient’s immune system) may be recommended.

When the melanoma spreads to multiple areas – Treatment options include:

• Chemotherapy - Chemotherapy is the use of cancer-fighting medications to stop the growth of malignant cells. Systemic (affects the entire body) chemotherapy with the medication dacarbazine (DTIC) may be used. DTIC is FDA-approved for treating melanoma. DTIC often is used in combination with another cancer medication(s) as research shows this can increase effectiveness. Another chemotherapeutic medication used to treat stage IV melanoma is temozolomide, which also may be administered alone or with other medication(s).
   

• Clinical trial – This is the method most often used to treat a patient with stage IV melanoma when the cancer spreads to multiple areas.
   

• Immunotherapy – Immunotherapy uses medication to stimulate or enhance the patient’s immune responses in order to fight established cancer. In stage IV, the systemic medication, interluekin-2 (IL-2), may be used.
   

• Palliative care - The purpose of this therapy is to relieve symptoms and improve a patient’s quality of life, not treat the cancer. Patients in all stages may receive palliative care. In advanced stages, palliative care can help control the symptoms and pain. Radiation therapy is used for this purpose in stage IV.

Follow Up: Key Part of Treatment
Melanoma can return and spread. After treatment, patients are taught how to carefully examine their own skin and lymph nodes for melanoma. Patients also are told about signs and symptoms, such as cough and chest pain, which may indicate that melanoma has spread. It is important to perform these examinations as instructed, be able to recognize signs and symptoms, and immediately report any changes to your doctor.

Studies show that the majority of metastases (spreads) and recurrences (melanoma returns) are discovered by the patient or a family member. One study found that self-examination may result in earlier detection of melanoma when it is still surgically curable.

Equally important, patients should keep all appointments for follow-up visits. Research shows that numerous metastases, local recurrences, and second primary melanomas are detected by a physician during routine examinations. During a routine examination, questions about the patient’s health are asked and a thorough physical examination is performed. Medical tests also may be necessary.

Recurrence
If melanoma recurs (returns), the patient may receive:

• Surgery to remove the tumor.
   

• Treatment via clinical trial. This may involve chemotherapy (medication used to kill cancer cells or stop them from dividing) or immunotherapy (treatment to help the patient’s immune system fight the cancer).
   

• Palliative care. When melanoma recurs, immunotherapy may be used to ease symptoms and improve the quality of life instead of treat the cancer. Easing discomfort rather than treating the condition is known as palliative care. Radiation therapy also may provide palliative care when melanoma recurs.

References:

American Academy of Dermatology, Guidelines of Care for Primary Cutaneous Melanoma. Approved by the Board of Directors March 2, 2001.

American Cancer Society and the National Comprehensive Cancer Network, Melanoma: Treatment Guidelines for Patients (version II). April 2004.

Otrompke J. “Melanoma immunology trials surveyed.” Dermatology Times, 2005 March;26(3):52.

Rigel DS. “Are Sentinel Lymph Node Biopsies Useful? Controversies and Clinical Recommendations,” Lecture delivered at 63rd Annual Meeting of the American Academy of Dermatology. New Orleans: February 2005.

Rogers GS and Braun, SM. “Prognostic Factors in Cutaneous Melanoma.” Dermatology Clinics of North America. Orlando, FL: W.B. Saunders Company; October 2002.
 

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