For Your Patients: What to Know about Treating Early-Stage Melanoma

Early-stage melanoma consists of stages 0-II and many types of stage III disease. Surgery plays a key role in all types of early-stage melanoma, and in many cases, may provide the only treatment necessary. Some stage III melanomas require drug therapy in addition to surgery, and in some cases of stage II melanoma, doctors will discuss the pros and cons of drug therapy after surgery.

Stage 0

Sometimes called melanoma in situ (Latin for "in the original place or position"), stage 0 tumors have not penetrated deeper than the top layer of skin (the epidermis) so they are not considered "invasive." The standard treatment is wide local excision surgery -- meaning removal of the melanoma and a margin of normal skin surrounding the skin tumor. If inspection under a microscope shows cancer cells at the edge of the sample, a second, wider excision of the area might be needed.

Stage I

Stage I melanoma has grown through the epidermis and into the second level of skin, known as the dermis. The tumor is still curable with surgery alone, and the same wide local excision approach is used. Occasionally, a doctor will recommend a sentinel lymph node biopsy (SLNB) for a melanoma that has a thickness of 0.8 to 1 mm based on additional risk factors. SLNB is recommended for stage IB melanoma (i.e., greater than 1-2 mm thickness without ulceration).

Stage II

Stage II melanoma includes tumors with a thickness of >1 to 2 mm and ulcerated or > 2 mm regardless of ulceration status. Stage II melanomas are invasive but remain in the dermis. Surgery with a wide-local excision remains the initial approach to treatment. Your doctor may recommend a SLNB to determine whether cancer cells have spread to one or more nearby lymph nodes.

A positive SLNB result means that cancer cells have spread to at least one nearby lymph node (the sentinel node) and might have spread to other nodes, which by definition, "upstages" the melanoma to stage III.

Even if the SLNB result is negative, if your disease is stage IIB or IIC, your doctor may recommend a drug called pembrolizumab (Keytruda) after surgery (adjuvant or adjunctive therapy), with the aim of reducing the risk of melanoma returning.

Stage III

Compared with other categories of early-stage melanoma, stage III is more complex in terms of the disease itself as well as the evaluation and the treatment options. Stage III means the melanoma has spread beyond the primary tumor to one or more lymph nodes or in the surrounding skin or dermis as "in transit" disease. Stage III is further divided into stage IIIA to IIID, representing increasingly larger or thicker lesions, the number of lymph nodes involved, multiple tumors, and other factors that increase the risk or complexity.

Your doctor may request an ultrasound and CT scans to determine the true extent of the disease or the source of certain signs or symptoms. Laboratory testing might be requested to determine whether a tumor has certain genetic mutations for which specific drugs have been developed (BRAF mutation).

Surgery is still the cornerstone of treatment for stage III melanoma, but because of the spread to one or more lymph nodes, surgery by itself is less likely to cure the melanoma. In addition to wide local excision surgery, treatment might include additional surgery to evaluate individual lymph nodes and determine how far the cancer has spread. If ultrasound shows that lymph node involvement is limited to the sentinel node, your doctor might decide to monitor other lymph nodes instead of performing additional surgery.

In some instances, clumps of cancer cells might appear in lymph vessels or under the skin between the primary tumor and a lymph node. Called in-transit melanoma, these cells are surgically removed whenever possible. Alternatively, anticancer drugs might be injected directly into in-transit tumors.

Adjuvant Therapy

Adjuvant drug therapy can help reduce the risk of the melanoma returning. Several options exist, and you and your doctor should discuss the pros and cons of the different options and decide which drug is best for you.

Immunotherapy

Also called immune checkpoint inhibitors, immunotherapy has greatly improved the effectiveness and tolerability of adjuvant therapy for melanoma. These drugs work by stimulating your body's immune (defense) system to attack the cancer. The most commonly used checkpoint inhibitors for stage III melanoma are nivolumab (Opdivo) and pembrolizumab. Another drug, ipilimumab (Yervoy), also is approved for adjuvant treatment of melanoma, but has largely been replaced by nivolumab and pembrolizumab.

Targeted Therapy

As the name suggests, this category of drugs is specific for (i.e., targets) the protein produced by genetic mutations that fuel the melanoma's growth. In particular, combination drugs that simultaneously target BRAF mutations have proven effective against melanomas that have the mutation. While there are three FDA-approved targeted therapy combinations, only dabrafenib (Tafinlar) and trametinib (Mekinist) are approved for adjuvant therapy in Stage III disease.

Radiation Therapy

In some cases, doctors recommend radiation therapy in addition to surgery, particularly for treatment of areas with involved lymph nodes or locally advanced disease.

Read previous installments in this series:

For Your Patients: What Is Melanoma?

For Your Patients: What You're Seeing Harmless or Is It Melanoma?

For Your Patients: Is It Melanoma or Something Else?

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.