The Conversation Has Changed For Stage III Melanoma


Stage III Melanoma—High Risk for Recurrence and (Now) Multiple Options

Stage III adjuvant treatment options were for many years limited and stark—because there were only two options. From 1995 until 2015 those options were surveillance or high-dose Interferon.

Those options were typically given to a patient by an oncologist after the patient’s primary tumor was surgically removed and there was a positive sentinel lymph node biopsy or other findings of regional metastases. The patient was told that Stage III melanoma is at high-risk for recurrence.

The conversation was difficult, mostly because the options didn’t offer much in terms of security that the melanoma wouldn’t return.

The two options were at opposite ends of the spectrum. On one end was active surveillance. Surveillance means the medical team follows the patient carefully, likely performing physical exams and imaging scans multiple times per year in order to look for signs of melanoma in the patient’s body. No medication is given, and therefore no side effects are experienced.

On the other end of the spectrum was Interferon, which was a controversial treatment for Stage III melanoma, given its well-known toxicity and questionable effectiveness.

The often brutal side effects included flu-like symptoms, fatigue, and neuropsychiatric symptoms. And by 2005, trials had shown that “among patients destined to recur, a year’s worth of high-dose Interferon treatment can delay the time of recurrence in a small subset, although for half of these patients this delay will be less than 1 year. However, the overall chance of recurrence and the overall survival is not improved.”1 In other words, the extreme toxicity was suffered for no overall survival benefit and only a small chance of delaying recurrence—not preventing it—in those who would recur.

But now the conversation is entirely different

There are potentially three options for Stage III patients—and high-dose Interferon is not one of them. Patients need to know that there are now options that do have proven effectiveness in preventing melanoma recurrence.

Before those options are even explained by an oncologist to a patient, however, the patient’s tumor will likely (and should) be tested for a marker called BRAF. If that test is positive, as it is approximately 50% of the time, the patient is eligible for targeted therapy.

Targeted therapy works by blocking certain proteins to stop the melanoma from growing. The treatment is a combination of drugs called Tafinlar and Mekinist. They are taken orally. Remember though, they are only for patients who test positive for BRAF.

The second option is immunotherapy, which uses medications designed to “awaken” the body’s immune system to fight stray melanoma cells and can be taken by all patients, regardless of BRAF status. Within the option for immunotherapy are several different drugs that are currently approved for Stage III adjuvant therapy—Keytruda, Opdivo, and Yervoy. These drugs are generally administered via IV.

Finally, active surveillance is still an option available to Stage III patients. Those whose melanoma has a relatively low recurrence risk (such as a Stage IIIa) or those who may not be able to tolerate the side effects of the new treatments are some who might select this option.

The conversation has indeed changed for medical oncologists and their Stage III patients because of new treatment options available.  AIM reminds all Stage III patients and families that conversations are two-way endeavors, and there is much for you to talk about with your oncologist.

  • Ask your oncologist if your tumor has been tested for the BRAF mutation.
  • Ask if you are Stage III A, B, C, or D and talk about what that means.
  • Ask which option s/he recommends for you—and why.
  • Talk through the plusses and minuses of each treatment.

To prepare for those conversations, read our recent In Plain English article, as well as our online guide called Options for Stage III Melanoma: Making the Decision That’s Right for You (see below).