Melanoma is a form of skin cancer that develops in the pigment-producing cells, or melanocytes, and is typically highly manageable when diagnosed in its localized stages. While many people associate cancer with rapid weight loss, this symptom is not typically present in the early phases of melanoma. Unexplained weight loss is instead a systemic sign that usually correlates with advanced or metastatic disease, where the cancer has spread beyond the original skin site.
Weight Loss in Advanced and Metastatic Melanoma
The occurrence of involuntary weight loss in melanoma patients is strongly correlated with the progression of the disease to advanced stages. Localized melanoma, encompassing Stage I and Stage II, rarely presents with this systemic symptom, as the tumor burden is minimal and confined to the skin or nearby lymph nodes. Weight loss becomes a more common concern in Stage III and Stage IV melanoma, which is defined by the cancer having spread to distant lymph nodes or other organs like the lungs, liver, or brain. The weight loss associated with advanced malignancy is often defined as an unexplained loss of 10 pounds or more without any intentional changes to diet or exercise.
Biological Drivers of Cancer-Related Weight Loss
The underlying mechanism for cancer-related weight loss is a complex metabolic syndrome known as cachexia. This condition is not simply starvation but a distinct biological process characterized primarily by the progressive loss of skeletal muscle mass, which may or may not include the loss of fat tissue. Cachexia is driven by systemic inflammation and metabolic dysregulation, not merely a reduction in caloric intake.
Advanced melanoma cells, along with surrounding host stromal and immune cells, release various signaling molecules called pro-inflammatory cytokines. Factors such as tumor necrosis factor-alpha (TNF-alpha) and interleukins are examples of these substances that circulate throughout the body. These cytokines disrupt the body’s normal metabolic balance by enhancing catabolic processes that break down tissue while simultaneously inhibiting anabolic processes that build and repair muscle. This results in a net muscle wasting effect, where the body’s resting energy expenditure may actually increase.
The inflammatory signals interfere with key signaling pathways that regulate muscle maintenance, such as suppressing the mTOR pathway responsible for muscle protein synthesis. This hypermetabolic state, coupled with a frequently observed loss of appetite, or anorexia, creates a severe energy deficit, leading to the profound weakness and physical deterioration that defines cachexia.
How Melanoma Treatments Affect Body Weight
Weight loss can also be a consequence of the medical interventions used to treat advanced melanoma, separate from the cancer’s direct effects. Treatments like immunotherapy, targeted therapy, and traditional chemotherapy can induce gastrointestinal side effects that severely limit the patient’s ability to eat or absorb nutrients. Nausea, vomiting, and diarrhea are common adverse events that reduce caloric intake and increase fluid loss, leading to weight decline.
Immunotherapies, such as checkpoint inhibitors, can lead to inflammation in the digestive tract, causing conditions like severe colitis or mucositis. Furthermore, these agents can trigger endocrine issues, specifically affecting the thyroid gland, which may lead to metabolic changes and subsequent weight fluctuations. Targeted therapies, which block specific proteins in cancer cells, also commonly cause severe fatigue, which can further suppress appetite.
Other Systemic Signs of Advanced Disease
Beyond weight loss, there are several other systemic indicators that may signal the presence of advanced melanoma that has spread to distant sites. One of the most frequently reported signs is profound, persistent fatigue that does not improve with rest. Other non-specific signs include unexplained fevers or chills that are not attributable to an infection. Patients may also experience drenching night sweats. Depending on the site of metastasis, patients often report new or persistent localized pain, such as bone pain or headaches, which serves as a more specific indicator of where the cancer has spread.