Advanced Melanoma

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This blog is for informational purposes only and should not be taken as medical advice. Content is sourced from third parties, and we do not guarantee accuracy or accept any liability for its use. Always consult a qualified healthcare professional for medical guidance.

What is Advanced Melanoma?

Advanced melanoma (stage III-IV) is a highly aggressive skin cancer originating from melanocytes, spreading to lymph nodes, skin, lungs, liver, brain, or bones. It accounts for 4% of skin cancers but most deaths due to its metastatic potential. In 2025, it’s a leading cause of skin cancer mortality, though immunotherapy and targeted therapies have significantly improved outcomes.

Symptoms

Symptoms include new or changing moles (asymmetrical, irregular borders, multicolored), skin lumps or ulcers, swollen lymph nodes, fatigue, weight loss, and site-specific symptoms like abdominal pain (liver metastases), persistent cough (lung spread), or neurological issues (headaches, seizures from brain metastases). Advanced cases may present with jaundice, bone pain, or skin nodules. Symptoms often emerge late, complicating early detection.

Causes

The primary cause is ultraviolet (UV) radiation from sun exposure or tanning beds, particularly in fair-skinned individuals. Genetic mutations (e.g., BRAF V600 in 50% of cases, NRAS), family history, multiple moles, and immunosuppression (e.g., HIV, transplants) increase risk. In 2025, research highlights how immune evasion and tumor microenvironment changes drive metastatic spread, with UV-induced DNA damage as a key initiator.

Diagnosis

Diagnosis involves skin biopsy of suspicious lesions, sentinel lymph node biopsy for staging, and imaging (CT, PET, MRI) to detect metastases. Molecular testing for BRAF, NRAS, or KIT mutations guides therapy. Liquid biopsies for ctDNA monitor disease progression and resistance. In 2025, AI-assisted dermoscopy and whole-genome sequencing improve diagnostic accuracy and subtype identification.

Treatment

Treatment for stage III includes surgery to remove primary tumors and lymph nodes, followed by adjuvant immunotherapy (nivolumab, pembrolizumab) or targeted therapy (BRAF/MEK inhibitors like dabrafenib/trametinib). Stage IV uses immunotherapy, targeted therapy, or combinations, with response rates of 50-60%. Radiation palliates brain or bone metastases, and intralesional therapies (e.g., T-VEC) treat skin lesions. In 2025, triplet therapies (immunotherapy + targeted) boost remission rates.

Future Outlook

In 2025, 5-year survival for stage IV melanoma is 35%, up from 18% a decade ago, driven by immunotherapy. Ongoing trials explore neoantigen vaccines, oncolytic viruses, and bispecific antibodies, with AI optimizing treatment selection. By 2030, personalized approaches could achieve 50% survival, with focus on preventing resistance and early metastasis detection.

Sources

The information for advanced melanoma is derived from NCI’s “Melanoma Treatment (PDQ®)” for treatment and prognosis details; Mayo Clinic’s “Melanoma” for symptoms and causes; WebMD’s “Melanoma Skin Cancer” for understanding and symptom descriptions; JAMA Oncology’s “Advances in Melanoma Therapy” for 2025 treatment updates; and PMC’s “Molecular Drivers of Melanoma Metastasis” for causes and future research directions.