Melanoma Stage 2 Response

Melanoma is a cancer that forms in the melanocytes (Brashers, Huether, & McCance, 2020).  According to Poklepovic and Luke, malignant melanoma is one of few cancers currently increasing in incidence.  New cases of malignant melanoma increased to more than 90,000 cases in 2018, up from approximately 74,000 cases in 2015 (Poklepovic & Luke, 2020).  In 2019, it was estimated that there would be 96, 480 diagnosed cases of melanoma in the United States, followed by approximately 7,230 deaths from the disease (Yushak et al, 2019).  A majority of diagnosed patients are treated with curative-intent surgical resection (Yushak et al, 2019).  However, patients with resected stage II or stage III melanoma are at increased risk for reoccurrence; whereas patients with stage IIA or stage IIIA disease have a melanoma-specific survival at five years of 94% or 93% (Yushak et al, 2019).  Patients with thicker primary melanomas (T3 or T4), ulceration, or more extensive lymph node involvement have a poorer prognosis (Yushak et al, 2019). 
Standard treatment for Stage II melanoma is wide excision therapy to remove the melanoma and a margin of skin around the site and sentinel lymph node biopsy (SLNB) (Poklepovic & Luke, 2020).  If the SLNB is negative, no further treatment is necessary, but close follow-up will remain important.  If the SLNB is positive, a lymph node dissection will likely be recommended, or monitoring by ultrasound every few months (Poklepovic & Luke, 2020).  Additionally, if the SLNB is positive for cancer, adjuvant (additional) treatment with an immune checkpoint inhibitor or targeted therapy drugs (if BRAF mutation exists) may be recommended to reduce the risk of reoccurrence (Poklepovic & Luke, 2020).  In BRAF mutant melanoma, targeted therapy offers a response rate of 60-70% with a median progression-free survival from 11 to 15 months (Poklepovic & Luke, 2020). 
Immunotherapy is treatment that includes use of medication to stimulate the patient’s own immune system to recognize and destroy cancer cells.  Immune checkpoint inhibitors target checkpoint proteins, which helps them restore the immune response against melanoma cells (American Cancer, Society, 2021).  These medications include pembrolizumab (Keytruda), nivolumab (Opdivo), atezolizumab (Tecentriq), and ipilimumab (Yervoy).  Ipilmumab has been associated with long-term survival in approximately 21% of treated patients with advanced melanoma (Poklepovic & Luke, 2020).  According to Poklepovic and Luke, pembrolizumab and nivolumab have confirmed survival outcomes and are considered the default standard of care for melanoma (2020).  Pembrolizumab and nivolumab have consistent response rates of 30-40% (Poklepovic & Luke, 2020).
Man-made versions of Interleukin-2 (IL-2) are occasionally used to treat melanoma as well.  While IL-2 can shrink advanced melanomas, it’s not used as frequently as in the past as immune checkpoint inhibitors have shown to be more effective with fewer side effects (American Cancer Society, 2021).  For earlier stages of melanoma, if the melanoma has reached nearby lymph nodes, it is more likely to appear in another part of the body; IL-2 may be injected into tumors to prevent spread (American Cancer Society, 2021).
Oncolytic viruses are lab altered viruses used to infect and kill cancer cells and alert the patient’s immune system to kill cancer cells.  Talimogene laherparepvec (lmlygic) is a oncolytic virus that is used to treat skin or lymph nodes that can’t be removed with surgery (American Cancer Society, 2021).  This virus is injected directly into tumors approximately every two weeks (American Cancer Society, 2021). 
Other, less frequently used treatments include the Bacille Calmette-Guerin (BCG) vaccine and Imiquimod cream.  The BCG vaccine may be injected directly into the tumor to activate the immune system (American Cancer Society, 2021).  Imiquimod cream is applied to skin to stimulate a local immune response against the melanoma cells; it may be used in cases where surgery could be disfiguring or against melanomas that have spread along the skin (American Cancer Society, 2021). 
American Cancer Society. (n.d.). Immunotherapy for Melanoma Skin Cancer.
Huether, SE., McCance, K.L., & Brashers, V.L. (2020). Understanding Pathophysiology.  Elsevier.
Poklepovic, A. & Luke, J. (2020).  Considering adjuvant therapy for stage II melanoma.  Cancer (126)6, 1166-1174.
Yushak, M., Mehnert, J., Luke, J., & Poklepovic, A. (2019). Approaches to High-Risk Resected Stage II and
III Melanoma. American Society of Clinical Oncology Educational Book, 39.

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