Guidelines for post-surgery treatment of patients with melanoma

In this study the Clinical Practice Guidelines in Oncology (NCCN Guidelines) in melanoma updated the 2016 recommendations on therapy after surgery and treatment of in-transit disease (when cancer cells are almost reaching the lymph nodes).

Melanoma incidence has been rising rapidly. Patient outlook and treatment options depend on the stage of disease at diagnosis. A panel of experts in the field of melanoma examined recent advances in treatment options. These Clinical Practice Guidelines off their recommendations for treatment of all stages of melanoma.

These guidelines are updated recommendations to treat melanoma patients after surgery and with in-transit disease.

Chemotherapy has been proven to not be effective in melanoma. Prior studies suggested that biochemotherapy (BCT; chemotherapy combined with immune therapy) helps the immune system to attack and kill cancer cells. BCT usually includes the immunotherapies interferon (IFN) or interleukin-2 (IL-2).

A previous study showed that, melanoma patients treated with BCT had improved recurrence levels (average of 4 years) compared to IFN alone (average of 1.9 years).

Immune therapy (such as ipilimumab – Yervoy) was also shown to significantly improve progression-free survival (PFS; time from treatment to progression) and overall survival in patients with inoperable melanoma.

The NCCN recommendations for treatment after surgery for stage 1 patients without lymph node metastasis (spread) are melanoma, observation or participation in a clinical trial. For patients with stage 2 melanoma, observation, participation in clinical trials or IFN is recommended.  For stage 3 patients, treatment with IFN, BCT or ipilimumab is recommended.

Radiation therapy (RT) can also be used as post-surgery treatment, especially in patients with high risk of local recurrence. A previous study showed that post-surgery RT was associated with improved local control and decreased risk of lymph node metastasis.

RT is also used after surgery for melanoma brain metastasis. Prior studies showed that post-surgery RT reduced disease progression with no benefit in overall survival.

The NCCN recommends the use of post-surgery RT in selected patients with positive lymph nodes and with a high risk of recurrence. Post-surgery RT to treat brain metastasis should be considered for these patients on a case-by-case basis.

The choice of treatments for patients with stage 3 melanoma with in-transit disease depend on the health of the patient, and the location and number of tumors. Surgery is the standard treatment for operable IND.

Different options are available for patients with inoperable disease. Injections directly into the tumor are possible treatment options. Injection of interleukin-2 or talimogene laherparepvec (T-VEC) directly into the tumor are an option. These injections induce tumor cell death. Side effects can include injection site reactions, fatigue, nausea, and flu-like symptoms. Other treatment options include laser therapy (cancer cells are killed by laser), imiquimod (a cream that helps the immune system to kill cancer cells) and RT.

In patients with an in-transit spread to one of the limbs, isolated limb perfusion may be considered. This involves the infusion of chemotherapy directly to the affected limb. One meta-analysis reported a response rate of up to 73%.

NCCN recommends surgery as the first treatment option for in-transit melanoma. For patients with inoperable disease the recommendation is for participation in a clinical trial. Otherwise, T-VEC is recommended, along with isolated limb perfusion in patients with metastasis to a limb.  Laser therapy, imiquimod or RT can help with local control or symptom reduction.

These NCCN guidelines are updated recommendations for the treatment of melanoma patients following surgery, and those with in-transit disease.