Treatments

The treatment of melanoma is typically determined by stage. Most melanomas are identified at an early stage and are treated with wide local excision and sentinel lymph node biopsy. At Spectrum Health we have a variety of treatments available for patients with stage III or stage IV melanoma as well. Our team of experts will meet to discuss your case and provide a comprehensive treatment plan tailored to your individual situation.

Contents:

• Surgical Treatments
  • Wide local excision
  • Sentinel lymph node biopsy
  • Regional lymphadenectomy
    • Axillary lymphadenectomy
    • Cervical lymphadenectomy
    • Inguinal lymphadenectomy
      • Minimally-invasive superficial inguinal lymph node dissection
      • Robotic deep inguinal lymph node dissection
• Medical Treatments
  • Immunotherapy
  • Targeted Therapy
  • Radiation Therapy
  • Regional Therapies
    • Talimogene Iaherparepvec
    • Isolated Limb Infusion

• The surgical approach to the treatment of melanoma is called wide local excision. Wide local excision involves removing the melanoma site along with an area of normal skin around the melanoma known as the margin. This excision contains the skin and fat underneath the skin down to, but not involving, the muscle.
• The width of the margin is determined by the depth of invasion (see Melanoma Details). The width is generally between 1-2 cm on all sides of the melanoma. For most areas of the body, in order to get the skin back together the incision must be three times longer than it is wide. In certain areas of the body where the skin is not pliable and wide margins are needed, a skin graft may be necessary.

• Sentinel lymph node biopsy (SLNB) is the method used to investigate the nearest lymph nodes to your melanoma. Though SLNB is a part of surgery, the process starts before your surgery begins when you arrive to the hospital. A radioactive substance is injected in the skin around the melanoma site in the Radiology area. Images are taken to reveal where the radioactive dye spreads. The purpose of the dye is to simulate the most likely route of spread of the melanoma. The radiologist will mark on your skin the approximate areas of the dye spread to help guide the surgeon in the operating room. Typical sites include the groin area for melanomas of the legs, under the armpit for melanoma of the arm, and the neck for melanomas of the scalp, face, and neck. Melanomas of the torso may go to one or more of these areas. It is important to remember that the dye traveling to a given area does not mean the melanoma has spread to that area, it just means that is the first place we should look for evidence of spread.
• Once you are taken to the operating room for surgery and are asleep, your surgeon will use a special probe to identify the signal from the radioactive dye. An incision is made over that area and the probe helps to find the lymph nodes deep below the skin. The lymph node or nodes containing the dye are removed and sent to the lab for analysis. In a typical sentinel lymph node biopsy only a few (1-4) lymph nodes are removed. The number removed depends on where the dye travels as any node that receives the dye is a potentially “at-risk” node for melanoma spread. The final pathology report that is receiving 3-5 business days after surgery will report whether or not the lymph nodes contained melanoma cells. The presence of melanoma cells in the lymph nodes may require further testing, surgery, and/or medical treatment (see Medical Treatment).
• Sentinel lymph node biopsy is a safe procedure with few complications. Potential complications include numbness (10-15%) and lymphedema (<6%).

In contrast to sentinel lymph node biopsy where only a few lymph nodes are removed, regional lymphadenectomy involve removal of a larger number of lymph nodes. This is performed in instances where there is proven cancer spread to the lymph nodes, though every case requires careful planning and regional lymphadenectomy is not necessary in all cases of lymph node spread. These procedures are divided by major lymph node groupings.

• Axillary lymphadenectomy, also known as axillary lymph node dissection, is a procedure to remove the lymph nodes from within the armpit. This is most commonly reserved for patients in whom the lymph nodes are large enough to be felt on physical exam (palpable lymph nodes) or seen on imaging studies. The procedure is accomplished through a large incision that runs beneath the hair-bearing portion of the armpit. The nodes are cleared out from under the armpit and sent to the pathology lab for analysis. The area removed by the surgeon is done by borders made up of muscles and veins that run under the armpit. The nodes are removed as a single “packet” rather than removing them one by one. Because of this, your surgeon will not know how many lymph nodes are removed at the time of surgery. Once the specimen is in the lab, the lymph nodes are separated out from the surrounding fat and examined for any signs of melanoma. The final report will include the number of lymph nodes removed and how many, if any, contain melanoma.
• After surgery you will have a drain placed under the armpit to help remove fluid from the space that was created during surgery. This drain may stay for a number of weeks. You will be given a log sheet to record the amount that comes out of the drain each day. Once this output decreases to a safe level the drain is removed in the office.
• Because more lymph nodes are removed during axillary lymphadenectomy, the risk of lymphedema of the arm is higher than sentinel lymph node biopsy and ranges from 10-30%. Range of motion is often limited in the initial period following surgery and physical therapy is commonly prescribed to regain function (see Cancer Rehab***). Long-term functional results with physical therapy are excellent. Other common complaints are numbness/tingling (30-50%) and fluid collections known as a seroma (15-20%) that may occur after the drain is removed. Two nerves that run through the armpit area are also at risk of injury and may be another focus for therapy if these nerves are not functioning normally after surgery.

• Cervical lymphadenectomy refers to removal of lymph nodes in the neck. These lymph nodes are divided in to “levels”. Your surgeon will decide which levels are appropriate for removal based on the location of the melanoma and which lymph nodes are involved. The nodes are cleared out from these levels and sent to the pathology lab for analysis. The nodes are removed as a single “packet” for each level rather than removing them one by one. Because of this, your surgeon will not know how many lymph nodes are removed at the time of surgery. Once the specimen is in the lab, the lymph nodes are separated out from the surrounding fat and examined for any signs of melanoma. The final report will include the number of lymph nodes removed and how many, if any, contain melanoma.
• A drain is typically utilized under the skin after surgery to prevent excess fluid accumulation. For cervical lymphadenectomy this often can be removed soon after surgery.
• Due to the location of lymph nodes in the neck, the risks for cervical lymphadenectomy are often associated with the nearby nerves. These include the nerves supplying facial muscles and those that help raise your shoulder. Injury to these nerves could result in temporary or permanent facial droop or inability to shrug the shoulder on the side of surgery. Fortunately, the vast majority of dysfunction is temporary after surgery. There is also potential risk to the salivary glands that are nearby.

Inguinal lymphadenectomy, also known as inguinal lymph node dissection, refers to removal of lymph nodes in the groin. Typically this involves a “superficial” inguinal lymph node dissection which is removal of lymph nodes in the groin that are under the skin. There are typically fewer lymph nodes in this area compared with those above and the procedure typically results in 8-12 lymph nodes removed. A “deep” inguinal lymph node dissection is rarely utilized but may be indicated in some cases of isolated spread to lymph nodes that are within the pelvis. At Spectrum Health we are one of only a few melanoma programs in the country to offer minimally-invasive approaches for both of these procedures.

• Traditional superficial inguinal lymph node dissection has been accomplished with a large incision that crosses the groin crease. Unfortunately this approach has been associated with a high rate of wound complications which can lead to delays in recovery. Minimally-invasive superficial inguinal lymph node dissection was developed as a safer, less invasive, way to accomplish removal of the lymph nodes in the groin. This is done through three small incisions near the middle of the thigh. A pocket is created under the skin that allows your surgeon to remove the lymph nodes similar to how they would when using the open technique. The lymph node “packet” is removed through one of these three incisions and a drain is left in place. The drain often needs to stay in for 4-6 weeks and in some cases stays in longer. You will be given a log sheet to record the amount that comes out of the drain each day. Once this output decreases to a safe level the drain is removed in the office.
• Minimally-invasive inguinal lymph node dissection has been associated with a reduction in wound complications of over 30% compared with the open approach. Though the technique is relatively new, cancer outcomes have not been compromised in comparison with the old technique. Because the number of lymph nodes removed is the same as for the open procedure, the rates of lymphedema are the same and range from 15-30%.

Deep inguinal lymph node dissection is reserved for cases where melanoma has spread only to these lymph nodes that are located deep within the pelvis. Often a large incision has been required to gain access to this area to remove the affected lymph nodes. At Spectrum Health we utilize a surgical robot to perform this procedure resulting in smaller incisions, less pain, and more rapid recovery. A series of small incisions are made in the abdominal wall and the abdomen is filled with carbon dioxide to create space for the surgeon to work. The robotic “arms” are delivered through these small incisions in to the abdomen where they are then controlled by the surgeon. The robotic system provides 3D vision for the surgeon and the robotic instruments allow for simulation of the movement of a normal human wrist. Though lymphedema of the leg is still a potential complication as with minimally-invasive inguinal lymph node dissection above, the robotic approach has been a wonderful improvement on this otherwise challenging procedure.

Perhaps the most significant advancement in melanoma care over the last decade has been the emergence of immunotherapy as a treatment options for melanoma. Though the process is very complex, in layman’s terms, the immunotherapy drugs unmask the melanoma’s ability to hide from the immune system which allows your own immune system to fight off the cancer. This was first introduced for patients with stage IV melanoma, melanoma that has spread to other organs or distant lymph nodes. With the success observed in stage IV melanoma, immunotherapy was then tested in stage III melanoma, when the only evidence of spread is to nearby lymph nodes. Immunotherapy has been shown to reduce the risk of recurrence by 20% in these patients and has now become the standard of care for patients with stage III melanoma following surgery. The most common drugs used are nivolumab (Opdivo®) and pembrolizumab (Keytruda®) and these drugs are given as infusions every 2-3 weeks for 1-year after surgical removal of stage III melanoma. There are many similar drugs being studied, along with investigating different ways of giving the drugs we already use. If immunotherapy is an options for you, a consultation will be set up with our Medical Oncology team to discuss the full risks and benefits associated with this treatment.

Targeted therapy drugs have been another major advancement in the care of melanoma patients. Approximately 40-50% of melanomas carry something called a BRAF mutation. This is an abnormality in the genetic makeup of the tumor itself and is not associated with gene mutations passed down from parents to children. BRAF inhibitor drugs were developed to block this pathway and prevent the melanoma from growing and surviving. While initially successful, recurrence rates were high with the first wave of BRAF inhibitor drugs. An escape mechanism was identified for how tumors worked around the BRAF inhibition leading to a second class of drugs known as MEK inhibitors. This combination targeted therapy is administered in pill form which adds to the convenience. Currently targeted therapy is used in selective cases of stage III and stage IV melanoma. If you have stage III or IV melanoma, our team will test your tumor for the BRAF mutation automatically to see if targeted therapy would be an option for you. Though being able to take a pill is an attractive option, these drugs do have side effects that can be significant. Our multi-specialty team will help to present the options for what is the best course of action tailored to your specific situation.

Radiation therapy is uncommonly used for melanoma, but may play a role for some patients. Radiation can be used in the setting of spread to the brain or in some patients with large or numerous lymph nodes affected by melanoma. Our expert team of Radiation Oncologists provide consultations for patients who are potential candidates for radiation therapy to discuss the pros and cons of this option.

• Talimogene laherparepvec, also known as TVEC or Imlygic®, is an exciting new form of immunotherapy. TVEC is a genetically modified version of the herpes simplex virus 1 that is commonly known for causing cold sores. TVEC is injected directly in to melanoma spots in the skin, under the skin, or in lymph nodes. Injection of TVEC improves recognition of the melanoma by the immune system, sometimes with dramatic responses. A “primer” dose is given followed by a waiting period of three weeks. Injections are then administered every two weeks. On average it takes 3-4 months to know whether or not TVEC will work for you. Sometimes new spots will pop up during treatment and these new spots are added to the cycle of injections.
• TVEC is associated with very few complications. Common symptoms are fevers, chills, and other flu-like symptoms for 24-48 hours after the injection. In many ways this is similar to receiving a flu vaccine. Injections are performed in the office setting and typically only take a few minutes to perform depending on how many spots there are to inject. TVEC is indicated for patients with “in-transit” melanoma, that is, numerous spots visible on or under the skin, or for lymph nodes that cannot be surgically removed. TVEC can also be used in patients with metastatic melanoma if there are spots that are accessible to injection. A member of our surgical team can discuss this option with you if you are a candidate.

Isolated limb infusion is used for locally-advanced or in-transit melanoma of the limb. In the operating room, catheters are placed inside the blood vessels of the affected limb by our Vascular Surgery team. Next, the limb is isolated from the rest of the body’s circulation using a tourniquet. A high-dose chemotherapy agent is then circulated through the limb via the catheters to treat the melanoma. The limb must be isolated from the circulation because the chemotherapy is too toxic to be given to the rest of the body. As part of the procedure, the limb does not receive blood flow for approximately one hour. Because of this, there can be damage to the muscles of the arm or leg resulting in significant swelling. You will be required to stay in the hospital for up to one week to monitor the swelling and muscle damage. Response rates are high with isolated limb infusion as tumors shrink or go away in 60% of cases. Newer reports using immunotherapy with isolated limb infusion have increased response rates to 85%. If you are interested in discussing isolated limb infusion, please set up a consultation with our surgical team.