Adjuvant Therapy

What is Adjuvant Therapy for Melanoma?

Adjuvant therapy is an additional treatment given after the primary treatment for a disease. In melanoma, adjuvant therapy is sometimes used after surgery to reduce the risk of melanoma returning. Some patients who undergo surgery for their melanoma may be at high risk of their melanoma coming back. That’s because sometimes microscopic melanoma cells can remain in your body, even if the surgery successfully removes all  visible melanoma tumors. Adjuvant therapy can help delay or prevent the recurrence of melanoma.


When is Adjuvant Therapy Given?

Before having surgery, your doctor may bring up the idea of adjuvant therapy and then discuss it in more depth with you again after surgery, once your melanoma has been staged (in order to determine if you are a candidate). Adjuvant therapy is typically started soon after surgery and commonly continues for one year.  


Who Should Consider Adjuvant Therapy?

Adjuvant therapy is often recommended for patients with high-risk melanoma following surgery. High-risk melanoma includes patients with:

  • Melanomas that are at least 2mm thick with ulceration (meaning the skin on the top of the melanoma has broken down); 
  • Melanomas over 4mm thick (with or without ulceration);
  • Melanomas that have spread to nearby lymph nodes, lymph vessels, or skin. 

Stages of Melanoma

Your age, overall health, and personal preferences should also be considered. The stage of your melanoma at diagnosis helps to determine your risk for recurrence after surgery. The melanoma’s depth and other characteristics of its site of origin (primary site), and whether nearby lymph nodes are involved, are all taken into account in the staging process. 

  • Stages 0 and I: Surgery is usually curative for early stage melanomas and the risk of recurrence is very low—estimated to be less than 2%. Therefore, adjuvant therapy is not recommended. 
  • Stages 2A: Surgery is usually curative for Stage 2A melanomas and adjuvant therapy is not typically recommended. 
  • Stage 2B and 2C: While surgery is often curative for patients with Stage 2B and 2C melanomas, these tumors have clinical features associated with higher risk of recurrence (thicker tumors and/or ulceration). Patients with Stage 2B and 2C melanoma should discuss possible benefits and risks of adjuvant therapy with their doctor.
  • Stage 3A: Although patients with Stage IIIA have lymph node involvement, the risk of recurrence is less than 20% and, therefore, adjuvant therapy is usually not recommended. To avoid the possibility of severe side effects with treatment, physicians often recommend close observation and treatment only if the melanoma returns. 

Individual circumstances vary greatly for patients with Stage III disease, so it is important to discuss treatment options with your physician.

  • Stages 3B, 3C, and 4: Patients in these groups have a high risk for recurrence and adjuvant therapy is often recommended if they have melanoma that is deeper or thicker (more than 4 mm thick) at the primary site or involves nearby lymph nodes. In Stage 4 – also called advanced melanoma – the cancer has spread to other organs such as the lung or brain.

Learn more about melanoma staging here.


Risks and Benefits of Adjuvant Therapy

Studies have shown that adjuvant therapy for melanoma can reduce the risk of your melanoma returning following surgery by up to 50%. For patients with high-risk melanoma, adjuvant therapy can be an important part of your treatment strategy. However, adjuvant therapies aren’t appropriate for all patients. That’s because all therapies – including those approved by the United States Food and Drug Administration (FDA) have potential risks. Some patients may experience only mild side effects, but permanent, severe, and even life-threatening side effects are possible. It’s important to talk about the possible benefits and risks with your doctor before making any treatment decision.    


Melanoma Adjuvant Therapy Options

Preferred Adjuvant Therapies:

The National Comprehensive Cancer Network (NCCN) is a non-profit alliance of 31 leading cancer centers throughout the United States. The NCCN provides treatment guidelines for clinicians and patients that are based on clinical research and these guidelines serve as “the recognized standard for clinical direction and policy in cancer care.” Therapies that have been shown to be the most effective and safe are designated as “preferred interventions” in the NCCN guidelines. 

  • Opdivo (nivolumab) and Keytruda (pembrolizumab), are both checkpoint immunotherapy medications and are considered the preferred agents for adjuvant therapy in melanoma. These medications may carry more risk for patients with autoimmune diseases or for patients undergoing immunosuppressive therapy for another medical condition. Patients receive nivolumab and pembrolizumab through an IV infusion. 

Learn more about Opdivo (nivolumab) here.

Learn more about Keytruda (pembrolizumab) here.

Common mild side effects include diarrhea, fatigue, and rash. More serious side effects that can occur include thyroid disorders, diabetes, a disorder of the pituitary gland called hypophysitis, and severe skin, heart, gastrointestinal, or lung reactions. Rarely, side effects can be life threatening.

  • Tafinlar (dabrafenib) + Mekinist (trametinib) is a targeted therapy combination that may be an alternative for patients whose cancer cells have a mutation called BRAF, especially for patients who are unable to undergo adjuvant immunotherapy due to an underlying medical condition. Patients take Tafinlar + Mekinist orally (swallowing by mouth).

Learn more about Tafinlar (dabrafenib) + Mekinist (trametinib) here.

Common mild side effects include fever, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, and muscle and joint pain. More serious side effects that can occur include bleeding, inflammation in the gastrointestinal tract, blood clots, heart failure, severe fevers, high blood sugar, or serious eye, lung, or skin reactions. Rarely, side effects can be life threatening.

  • Adjuvant Therapy Clinical Trials test treatments or methods that have not yet been approved by the FDA. Joining a clinical trial is a viable treatment option for people with melanoma and all cancers, and participation often represents patients’ best access to cutting-edge research. There are many clinical trials that are looking at how best to reduce risk of melanoma returning. Learn more about clinical trials and find possible trial matches here.

Regardless of which treatment approach patients might choose, it is very important to report any side effects that you experience—both mild and serious—to your care team!

Other FDA Approved Adjuvant Therapies:

In rare circumstances, older therapies may still be used, particularly for patients at high risk for recurrence who cannot take newer immunotherapies due to other conditions or contraindication.

  • Yervoy (ipilimumab) is approved as a single agent for adjuvant therapy in melanoma, but it has largely been replaced by nivolumab or pembrolizumab since these agents are often better tolerated. 

Learn more about Ipilimumab (Yervoy) here.

  • Intron and Sylatron (interferon) is an older therapy that is now rarely used since studies have shown that newer therapies are more effective and have far fewer side effects. However, it is still FDA approved and still can be considered in specific situations. 

Learn more about interferon (Intron & Sylatron) here.

Other Therapies:

  • Opdivo + Yervoy is not currently FDA approved as an adjuvant therapy, however some doctors may still recommend the combination, followed by nivolumab alone, in specific situations. The combination is believed to be more effective than PD-1–based immunotherapy (nivolumab or pembrolizumab monotherapy), but is used only in specific situations because of its increased risk of adverse events compared to single-agent immunotherapy. The combination is currently FDA approved for metastatic melanoma that is not treatable with surgery.
  • Opdualag is not currently FDA approved as an adjuvant therapy, however clinical trials are underway to test its effectiveness in this setting. Talk to your doctor about available clinical trials.

It is very important that you report all side effects—both mild and serious—to your care team!


Questions to Ask About Adjuvant Therapy: 

  • Is adjuvant therapy a good option for treating my melanoma?
  • Could we discuss the pros and cons of adjuvant therapy for my situation?
  • If I start adjuvant therapy, and still experience a recurrence, how do my future treatment options change?
  • When will I start adjuvant therapy?
  • Are there other additional factors beyond stage that can help assess whether I have a high-risk of melanoma recurrence?
  • What are the side effects of the treatment you recommend?
  • Are there any clinical trials that I would qualify for?

Melanoma Research Alliance

The Melanoma Research Alliance is the largest, non-profit funder of melanoma research worldwide. Since 2007, we have directly funded over $143 million in innovative grants to improve prevention, detection, and treatment of melanoma. Learn more about our funded research.

Last updated: May 2022 

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