Advanced melanoma

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Advanced melanoma is Stage 4 melanoma and unresectable stage 3C and 3D melanoma.

What is unresectable Stage 3C and 3D melanoma?

Stage 3 melanoma is melanoma which has spread (metastasised) beyond the original skin site (the primary site) either to nearby skin (sometimes called in transit disease) or to nearby (regional) lymph nodes. For many patients, surgery is the best choice of treatment and the aim of surgery is to cure you. This is described in our Section on Stage 3.

View stage 3 information

However sometimes surgery is not the right approach. This might be because surgery has already been tried, sometimes on more than one occasion, but the melanoma has come back again. Alternatively, the melanoma may be covering too large an area for surgery to have a realistic chance of controlling the disease or because the extent of the surgery would make recovery very difficult. In this case the melanoma is considered to be advanced (sometimes called unresectable) and your medical team will need to consider non-surgical approaches to try and control your melanoma.


If your melanoma is considered inoperable, you may be considered for immunotherapy or BRAF targeted therapy.

Immunotherapies are drug treatments that aim to enhance your own body’s immune system so that it an recognise and destroy cancer cells more effectively.  By enhancing the immune system, it is common for healthy parts of the body to be affected too.  There are now a number of immunotherapy treatments available that may be offered to you.  They are given via an intravenous drip, usually in hospital.  A single immunotherapy treatment or a combination of two different immunotherapy treatments may be administered.

> See our page on Immunotherapy

BRAF-targeted therapy

Your melanoma should be tested to see if it carries a faulty BRAF gene. This is a mistake (mutation) that develops in the BRAF gene in around half of melanomas. It is NOT a genetic mutation that you can pass down to your children. If your melanoma is BRAF mutantit produces an over-active BRAF protein which drives the growth of the melanoma. It is important to know whether your melanoma  has the BRAF mutation as this may give you the option of treatment with BRAF-targeted therapy

View our video below for further information on BRAF mutation

Your medical team may also test your melanoma for other genetic mutations – for instance some melanomas have mistakes in the NRAS or c-KIT gene. Although there is much less evidence that targeting these mutations can be helpful, this information may increase the treatment options your medical team can discuss with you – for instance in opening up opportunities to take part in clinical trials.

>See more information on targeted therapy

Other options for treatment your medical team may discuss with you

Although immunotherapy and BRAF-targeted therapy are the most common treatments used for advanced Stage 3C/D melanoma, your medical team may consider other treatments, depending on your situation. These may happen alongside or instead of immunotherapy or BRAF-targeted therapy.


Although your medical team might not feel that surgery will cure your melanoma, they are still likely to consider whether surgery might help control your disease. It is always important that you  understand what surgery might or might not be able to achieve for you, and what the risks of any operation might be

Dr Elaine Vickers, Cancer Science Communicator, explains what is involved in T-VEC treatment (talimogene laherparepvec).

Learn more about other treatments when your melanoma cannot be removed with surgery

Clinical trials

Clinical trials are an essential step in improving the care we are able to offer to patients with melanoma. They help us learn about whether new treatments work, and how to use them most effectively. Taking part in clinical trials might offer you the opportunity to access a new treatment before it is more widely available and will help the melanoma community move forward in its knowledge and understanding of this disease. It is important to bear in mind that not everyone in clinical trials will receive new treatments – many trials compare new treatments with standard treatments and you will not be able to choose which group you are allocated to. Clinical trials all have strict criteria about who can take part and so even if you are keen to take part in a clinical trial, it may not be possible for you to be included.

> See our page about clinical trials 

>Search for clinical trials on our Melanoma Trialfinder 

UnresectableStage 3C/D melanoma: Questions you may have for your medical team

  • Where has my melanoma spread to?

  • Will my melanoma be tested for BRAF mutation?

  • If I am BRAF positive, what does that mean for my treatment?

  • If I am BRAF negative, what does that mean for my treatment? Will I be tested for NRAS or c-Kit mutation?

  • What treatment options are available for me?

  • What are the advantages and disadvantages of these options?

  • How important is it to have oral treatment or treatment in hospital?

  • How much time will I spend having treatment?

  • How could the treatment affect my lifestyle and work?

  • What are the possible side effects of the treatments?

  • What clinical trials could I potentially be considered for?