Patient education: Melanoma treatment; localized melanoma (Beyond the Basics)

MELANOMA OVERVIEW — Melanoma is a serious form of skin cancer that starts in the pigment-producing skin cells (melanocytes). Melanoma is the fifth most common cancer in the United States, and the number of melanoma cases diagnosed annually is increasing faster than that for any other cancer. Although the explanation for this is unknown, it may be related to increased recreational sun exposure and global changes, such as ozone depletion.

In contrast to other types of skin cancers (eg, squamous cell or basal cell cancers) that usually develop on sun-exposed areas of the body, melanomas can develop anywhere on the skin surface, including the palms of the hands and soles of the feet, as well as on the mucous membranes lining the mouth, nose, and genital areas. If left untreated, melanoma can spread (metastasize) to other parts of the body much more frequently than is typical for other types of skin cancers. Fortunately, when detected at an early stage, melanoma treatment is often effective in preventing the spread of the disease.

This topic reviews the diagnosis and treatment of localized melanoma. A separate topic discusses the treatment of advanced and metastatic melanoma. (See "Patient education: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics)".)

CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.

In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.

MELANOMA DIAGNOSIS

Appearance of a lesion — Similar to other types of skin cancer, melanoma is diagnosed based upon the appearance of a skin lesion. Melanomas usually present as a changing mole or a new mole, most often with dark pigment. They can occur anywhere on the skin surface, including on the back, the scalp, and other areas that may be easy to miss with self-inspection. Abnormal findings can be described with an acronym, ABCDE (picture 1):

●A – Asymmetry (one side is different from the opposite side)

●B – Border irregularities (jagged, uneven edge)

●C – Color variegation (ie, different colors within the same region)

●D – Diameter greater than 6 mm (if larger than a pencil eraser, evaluation recommended)

●E – Evolution (change) in color, shape, or symptoms over time

Other abnormal features include inflammation (redness around the mole or swelling), and bleeding or crusting. While the majority of melanomas are pigmented (have color), the lesion can occasionally lack pigment and be the same color as the surrounding skin. They can also look like a blood blister or a tick bite. A person who notices any of these changes should make an appointment with a health care provider as soon as possible. Referral to a dermatologist (a physician who specializes in skin conditions) may be recommended.

Biopsy — To determine if the abnormality is a melanoma, a small piece of the abnormal skin lesion (or if it is small, the entire area) is removed. A biopsy deep enough to include the deepest part of the lesion is preferred. The biopsy is then examined under a microscope to determine if precancerous or cancerous cells are present.

MELANOMA CLINICAL STAGING — Once melanoma is diagnosed, the next step is to determine the clinical stage or extent of disease spread. Accurate staging is important to determine the most appropriate treatment.

The American Joint Committee on Cancer (AJCC) has defined a staging system for melanoma that takes into consideration the following characteristics:

●Thickness of the tumor

●Ulceration (loss of skin) over the surface of the melanoma

●Involvement of the "regional" (nearby) lymph nodes and/or the lymphatic vessels that lead to them

●Evidence of tumor spread beyond the lymph nodes (distant metastases)

Another metric, the "mitotic rate" (number of dividing cells in the tumor per square millimeter), is not used in AJCC staging, but it influences prognosis (how the disease will progress).

A thorough history and physical examination are typically performed to evaluate the possibility of lymph node or distant spread of the tumor.

Imaging tests may also be recommended, particularly for patients with advanced melanoma, those with a previous melanoma, and those with signs or symptoms that might be suggestive of metastasis. Possible tests include a chest X-ray, computed tomography (CT) scan, positron emission tomography (PET)/CT, or even a brain magnetic resonance imaging (MRI) scan. Further, such imaging is frequently indicated if the lymph nodes are evaluated and found to be involved. (See 'Evaluating the lymph nodes' below.)

Surgery — In most patients, surgery is required to remove (or excise) the entire melanoma. Generally, 1 to 2 cm (approximately 0.4 to 0.8 inches) of normal skin surrounding the entire lesion must also be removed. This procedure is called a wide local excision. This decreases the chance that the melanoma will recur at the same site.

The type of physician (eg, dermatologist, general surgeon, cancer surgeon, head and neck surgeon, or plastic surgeon) who will perform the surgery depends upon the location and size of the wide local excision. Most procedures are performed as a day surgery in a hospital or surgical center. Most patients are able to go home later the same day.

Occasionally, skin grafting may be necessary to promote healing and replace skin that has been removed. In some patients (such as those with a melanoma on the face or neck), it may be difficult to remove a sufficient amount of normal skin to ensure adequate margins. In such cases, it is critical to make certain, at a minimum, that there are no tumor cells extending to the resection margins (ie, the edges of the area of skin that was removed).

If an enlarged lymph node (gland) is present, it may be biopsied, often prior to the wide local excision, to aid in surgical planning. Even if enlarged lymph nodes cannot be detected, the lymph nodes frequently will be evaluated during the wide local excision procedure.

Evaluating the lymph nodes — The most common site of melanoma spread is the lymph nodes draining the area of skin where the melanoma was detected. Sometimes, lymph node involvement is obvious because an enlarged lymph node can be felt. In this case, removal of all the lymph nodes in that area (called a therapeutic node dissection) is the standard approach. Therapeutic node dissection provides an opportunity for cure of the melanoma. When surgery is used in conjunction with adjuvant systemic (body-wide) therapy, the opportunity of cure may be improved. (See 'Melanoma adjuvant therapy' below.)

In the majority of cases, enlarged lymph nodes are not visible or palpable, and the only way to determine if lymph nodes are affected is to take a sample of the draining lymph node during surgery. This is typically accomplished with a surgical technique known as sentinel lymph node (SLN) biopsy.

Sentinel lymph node biopsy — The SLN technique is based upon the theory that when tumor cells migrate, they spread to one or a few lymph nodes before involving other nodes. These nodes can be identified by injecting a blue dye or radioactive material around the primary tumor before the wide local excision, and then searching for the node that has absorbed the dye or the radioactive tracer at the time of surgery. This is known as lymphatic mapping.

Lymphatic mapping and SLN biopsy are usually done at the time of the wide local excision. Most procedures are performed in a hospital after the patient is given general anesthesia to induce sleep and prevent pain. The patient may go home later the same day or the following day.

The status of this first draining (sentinel) lymph node accurately predicts the status of the remaining regional lymph nodes. Because only one lymph node is removed (or at most, a few), the risk of this procedure is lower and the accuracy is greater than a full lymph node dissection. After the lymph node is removed, it is then thoroughly examined under a microscope to determine if melanoma cells are present.

The success of a SLN biopsy is dependent upon the skill of the surgeon and the other physicians involved with the procedure. If the biopsy comes back positive (meaning it showed cancer cells), the person can be monitored with observation and ultrasounds at regular intervals. Then, if an exam or ultrasound shows cancer in the regional lymph nodes, these lymph nodes will be removed in a procedure called a "completion lymph node dissection." Avoiding or delaying the removal of the regional lymph nodes reduces the risk of a complication called lymphedema, which is a swelling caused by buildup of fluid in a limb near where the nodes were.

If the SLN biopsy identifies the draining lymph node and it comes back negative, further lymph node dissection is not performed since the likelihood of finding tumor involvement is less than 5 percent.

When is SLN biopsy recommended? — SLN biopsy has become the standard technique for assessing the regional lymph nodes and is recommended for staging of most people with newly diagnosed melanomas. However, certain people whose melanomas are very thin (<0.8 mm [0.3 inches] as measured under the microscope) and who do not have other high-risk features likely do not require SLN biopsy since the likelihood of tumor spread to the regional lymph nodes is less than 5 percent.

MELANOMA PATHOLOGIC STAGING — Once the staging workup is complete, a pathologic disease stage between I and IV is assigned. A higher stage indicates more extensive disease.

●Stage I or IIA disease – The tumor is less than 4 mm (0.16 inches) thick without ulceration, or less than 2 mm (0.08 inches) thick if ulceration is present. This is considered to be localized disease. Surgery alone is curative in 80 to 90 percent of cases, meaning the cancer is completely removed and not likely to return.

●Stage IIB or IIC disease – The tumor is 2.1 to 4 mm (0.08 to 0.16 inches) thick with ulceration, or 4 or more mm (0.16 inches) thick with or without ulceration. This is considered to be localized disease. Patients are at a higher risk of recurrence, even after the tumor has been completely surgically removed. Adjuvant (additional) therapy is often recommended, especially for tumors that are 4 or more millimeters (0.16 inches) thick. (See 'Melanoma adjuvant therapy' below.)

●Stage III disease – There is evidence of melanoma spread in the lymphatic channels surrounding the tumor (called satellites) or nearby lymph nodes. The tumor may be any thickness. Adjuvant therapy is strongly recommended. (See 'Melanoma adjuvant therapy' below.)

●Stage IV disease – The melanoma has metastasized to more distant locations in the body, which may or may not include the lymph nodes. The tumor may be any thickness or, in some cases, the primary melanoma is not found (this is called "unknown primary"). This is referred to as advanced disease. A full discussion of the treatment of advanced melanoma is available separately. (See "Patient education: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics)".)

Based upon the pathologic disease stage, the optimal treatment is chosen. For patients with localized disease who have no evidence of distant metastases, the goals of treatment are:

●Complete surgical removal of the primary melanoma

●Evaluation of regional lymph nodes for evidence of tumor involvement

●Preventing further spread or disease recurrence

MELANOMA ADJUVANT THERAPY — The term "adjuvant therapy" refers to any additional anticancer treatment that is given after a cancer is surgically removed. The goal of adjuvant treatment is to stop or slow the growth of any remaining cancer cells that were not removed during surgery and to decrease the risk of recurrence. Immune therapy (also called immunotherapy) refers to drugs that work with your immune system to do this. Targeted therapy (treatments that are directed at a particular abnormality or mutation) has also been used for this purpose.

Other experimental approaches are being developed as well, but they have not yet been approved for use in this setting. Participation in formal clinical trials should be considered whenever possible.

Immune therapy — The drugs nivolumab and ipilimumab, called "checkpoint inhibitors," are agents that enhance the body's immune reaction against melanoma and have been used as adjuvant therapy for people with melanoma who are at high risk for recurrence.

Nivolumab — Nivolumab (brand name: Opdivo) is a type of drug, called an "anti-PD-1 checkpoint inhibitor," that also uses the body's immune system to reject the cancer. Nivolumab is given by IV either every two weeks or every four weeks for one year if there are no severe side effects. Although nivolumab can also cause serious side effects due to the immune system attacking other parts of the body, these side effects were found to be less frequent and less severe than with ipilimumab. Nivolumab has replaced ipilimumab as the one of the preferred immunotherapy drugs for adjuvant use in patients at high risk for recurrence.

Pembrolizumab — Pembrolizumab (brand name: Keytruda) is another anti-PD-1 checkpoint inhibitor, similar to nivolumab, that also uses the body's immune system to reject the cancer. Pembrolizumab is given by IV either every three weeks or every six weeks for one year if there are no severe side effects. Although pembrolizumab can also cause serious side effects due to the immune system attacking other parts of the body, these side effects were found to be less frequent and less severe than with ipilimumab. Pembrolizumab has replaced ipilimumab as one of the preferred immunotherapy drugs for adjuvant use in people at high risk for recurrence.

Ipilimumab — Ipilimumab (brand name: Yervoy) is an "anti-cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor" that unleashes the body's immune system so it can reject the cancer. Ipilimumab is given by IV once every three weeks for four doses, generally in combination with nivolumab.

Ipilimumab can cause the immune system to attack other parts of the body in addition to the cancer cells; this has led to a wide range of serious and potentially fatal side effects. The most common of these include skin reactions, diarrhea and colitis, liver toxicity, and endocrine abnormalities.

Targeted therapy — Targeted therapy with the combination of dabrafenib and trametinib has also demonstrated significant improvement in survival for patients at high risk of recurrence. These agents have not been compared with immunotherapy, and their use is limited to patients with specific mutations.

MELANOMA MONITORING

Clinician monitoring — Because melanoma can recur in the same location or at new sites, routine follow-up and monitoring are very important. Seeing a health care provider regularly is the most important aspect of follow-up since most recurrences are discovered when the patient is seen and examined at regular intervals after treatment.

Imaging studies (eg, CT or positron emission tomography [PET] scans) are usually recommended only if new symptoms or physical exam, blood test, or chest X-ray abnormalities develop. These more advanced imaging studies may also be done on a regular basis for the initial two to three years in patients with high-risk stage III disease with palpable lymph nodes.

Self-examination — In addition to visits with a health care provider, monthly self-examination is recommended to identify any new or changing skin lesions. If you notice a new or changing mole or lesion, contact a health care provider to determine if further evaluation is needed.

●To perform self-examination, stand in an area that is brightly lit. Use a handheld mirror to examine your face, including the nose, lips, mouth, and ears. Face away from a full-length mirror and hold up the handheld mirror to see the back of your head, ears, and neck.

●Examine both sides of your hands and arms, including between the fingers and under the fingernails. Use the full-length mirror to examine the undersides and back of your arms and armpits. Examine your neck, chest, and abdomen. Females should lift the breasts to examine underneath.

●Using both mirrors, examine your shoulders, upper back, and upper arms. Scan your lower back, buttocks (including between the buttocks), and the backs of both legs.

●Sit down, and rest one foot on a chair. Examine your legs, including the ankles, the top and bottom of the feet, between the toes, and under the toenails. Switch legs, and repeat. Use a handheld mirror to examine your genitals.

Prevention of future melanoma — People who have had melanoma are at increased risk of developing melanoma again. Ways to reduce exposure to ultraviolet (UV) radiation from sunlight are discussed separately. (See "Patient education: Sunburn prevention (Beyond the Basics)".)

CLINICAL TRIALS — Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

●www.cancer.gov/about-cancer/treatment/clinical-trials

●https://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Melanoma skin cancer (The Basics)
Patient education: Sunburn (The Basics)
Patient education: Seborrheic keratosis (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics)
Patient education: Sunburn prevention (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Adjuvant and neoadjuvant therapy for cutaneous melanoma
Evaluation and management of regional nodes in primary cutaneous melanoma
Imaging studies in melanoma
Surgical management of primary cutaneous melanoma or melanoma at other unusual sites
Primary prevention of melanoma
Melanoma: Epidemiology and risk factors
Screening for melanoma in adults and adolescents
Staging work-up and surveillance of cutaneous melanoma

The following organizations also provide reliable health information.

●National Cancer Institute

      1-800-4-CANCER

      (www.cancer.gov/)

●American Society of Clinical Oncology

(www.cancer.net/)

●American Cancer Society

1-800-ACS-2345

(www.cancer.org)

●National Library of Medicine

(https://medlineplus.gov/healthtopics.html)

●The Melanoma Center, University of Pittsburgh Cancer Institute

(http://hillman.upmc.com/cancer-care/melanoma-skin/program)

●Skin Cancer Foundation

(www.skincancer.org/)

●Melanoma Research Foundation

     (https://melanoma.org/)