Zehn Skin and Health

By Bobak Thomas Pousti, MD

Skin Cancer: Trends, Risk Factors, and Treatment Options

Skin cancer is the most prevalent cancer in the United States, affecting an estimated one in five Americans during their lifetime 1. This comprehensive review examines the trends in skin cancer incidence and mortality, explores the correlation with various risk factors, and provides an overview of treatment options, including systemic therapies and non-traditional approaches.

Skin Cancer Incidence and Mortality

Overall Trends

The incidence of skin cancer has been steadily increasing over the years. This rise is likely attributed to a combination of factors, including increased sun exposure, improved detection methods, and an aging population 2. Notably, there was a substantial increase in the incidence of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) between 1976-1984 and 2000-2010, with BCC incidence rising by 145% and SCC incidence increasing by 263% 3. Non-melanoma skin cancers (NMSC), encompassing BCC and SCC, are the most common types, with approximately 5.4 million cases diagnosed annually in the US 2. Melanoma, while less frequent, is the most aggressive form of skin cancer, responsible for the majority of skin cancer-related deaths 3.

Skin Cancer by Type

The following table summarizes the incidence and mortality rates of different skin cancer types in the US:

Skin Cancer TypeIncidence (US, 2024)Mortality (US, 2024)
Melanoma100,640 invasive cases 3 (1% of all skin cancers 4)8,290 deaths 3
Basal Cell CarcinomaMost common type 2
Squamous Cell CarcinomaSecond most common type 5
  • Melanoma: Melanoma incidence has been rising rapidly, with rates doubling between 1982 and 2011 3. Geographical variations in melanoma incidence are observed globally, with higher rates in some regions compared to others 6.
  • Basal Cell Carcinoma: BCC is the most frequent type of skin cancer 2. Age-adjusted incidence rates for BCC have increased significantly, with a more pronounced rise in men than in women 7.
  • Squamous Cell Carcinoma: SCC is the second most common form of skin cancer 5. Its incidence has been steadily increasing, with a nearly three-fold rise observed from the 1970s to the early 2000s 5.

Mortality Rates

While NMSCs have high survival rates when detected and treated early, melanoma presents a more serious prognosis. The five-year survival rate for melanoma identified before it spreads to the lymph nodes is 94% 3. However, this rate decreases to 74% when the cancer reaches nearby lymph nodes and 35% when it metastasizes to distant organs 3. It is crucial to note that delayed treatment can significantly impact melanoma survival rates. Compared to patients treated within 30 days of biopsy, those treated 30 to 59 days after biopsy have a 5% higher risk of mortality, and those treated more than 119 days after biopsy have a 41% higher risk 8. In 2024, an estimated 8,290 deaths in the US will be attributed to melanoma 3.

Demographic Breakdown

Age

Skin cancer risk generally increases with age. In the UK, nearly half of all new non-melanoma skin cancer cases are diagnosed in individuals aged 75 and older 9. For melanoma, the average age at diagnosis is 66, but it is also prevalent among young adults, particularly young women 10.

Gender

Men have a higher incidence of melanoma compared to women and tend to experience worse outcomes, including lower survival rates for advanced melanoma 11. This difference may be influenced by behavioral factors, such as men spending more time in the sun and being less likely to use sunscreen 12. Men also exhibit a higher incidence rate of NMSCs than women 13.

Race/Ethnicity

Melanoma is more common in individuals with lighter skin tones 10. White populations have the highest risk of melanoma compared to other racial groups, with a lifetime risk of approximately 3% (1 in 33) for White individuals, 0.1% (1 in 1,000) for Black individuals, and 0.5% (1 in 200) for Hispanic individuals 10. However, it is essential to recognize that skin cancer can affect people of all skin colors 3. While melanoma is less prevalent in individuals with darker skin tones, they often present with more advanced disease at diagnosis and have lower survival rates compared to their White counterparts 14. This disparity underscores the need for increased awareness and early detection in these populations.

Correlation with Other Factors

Sun Protection Use

Excessive exposure to ultraviolet (UV) radiation from sunlight or indoor tanning beds is a primary risk factor for all types of skin cancer 3. Regular and proper sunscreen use can significantly reduce the risk of developing melanoma and SCC 16.

Lifestyle

Lifestyle factors, such as smoking, alcohol consumption, and circadian rhythm disruption, have been associated with an increased risk of skin cancer 17. Maintaining a healthy lifestyle, which includes regular exercise, stress management, and adequate sleep, can contribute to overall well-being and potentially reduce skin cancer risk 18.

Diet

Studies suggest that a diet rich in antioxidants, vitamins (C, E, A, and D), and omega-3 fatty acids may play a role in skin cancer prevention 19. These nutrients are found in various foods, including fruits, vegetables, fatty fish (such as mackerel, sardines, and salmon), and whole grains 20. Vitamin D, in particular, has been shown to have potential benefits in skin cancer prevention, and it can be obtained from sources like fatty fish, milk, cheese, and fortified orange juice 20.

Obesity

The relationship between obesity and skin cancer is complex and not fully understood. Some studies indicate an inverse association between obesity and NMSCs, possibly due to reduced sun exposure in individuals with obesity 21. However, other research suggests that obesity may increase the risk of melanoma and potentially lead to worse outcomes 22.

Environmental Products/Toxins

Exposure to certain environmental toxins, including arsenic, pesticides, and industrial pollutants, has been linked to an increased risk of skin cancer 23. Occupational exposure to these toxins is a significant concern for individuals working in industries such as agriculture, manufacturing, and construction.

Treatment Options

Melanoma

Treatment for melanoma typically begins with surgery to remove the tumor 24. Depending on the stage and characteristics of the melanoma, other treatments may be used in conjunction with surgery or as alternatives. These include:

  • Immunotherapy: This treatment harnesses the body’s immune system to fight cancer cells. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have shown promising results in treating advanced melanoma 25.
  • Targeted therapy: This therapy focuses on specific molecules involved in cancer cell growth. Targeted therapies, such as BRAF and MEK inhibitors, are used for melanomas with specific gene mutations 25.
  • Chemotherapy: Chemotherapy drugs, such as dacarbazine and temozolomide, may be used to control melanoma that doesn’t respond to other treatments 24.
  • Radiation therapy: Radiation therapy uses high-energy rays to kill cancer cells. It may be used to treat melanoma that has spread to other parts of the body or cannot be removed surgically 25.

Basal Cell Carcinoma

Treatment for BCC typically involves removing the cancer from the body. Treatment options include:

  • Surgery: Surgical excision, Mohs surgery, and curettage and electrodesiccation are common surgical procedures used to remove BCC 26.
  • Radiation therapy: Radiation therapy may be used for BCC in areas that are difficult to treat surgically, such as the eyelid or ear 27.
  • Cryotherapy: Cryotherapy involves freezing the cancerous lump to destroy it 28.
  • Topical treatments: Prescription creams or ointments may be used for small and thin BCCs 26.

Squamous Cell Carcinoma

Treatment for SCC often involves surgery to remove the tumor, followed by additional treatments to destroy residual cancer cells 29. Treatment options include:

  • Surgery: Excisional surgery, Mohs surgery, cryosurgery, and laser surgery are surgical options for SCC 30.
  • Radiation therapy: Radiation therapy may be used for SCC that has spread to lymph nodes or other parts of the body 31.
  • Topical medications: Skin creams containing imiquimod or 5-fluorouracil may be used to treat SCC in the top layer of the skin 32.

Systemic Therapies

Systemic therapies are treatments that affect the entire body and are often used for advanced skin cancers or those that have spread to other parts of the body.

Currently Available Systemic Therapies

  • Immunotherapy: Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, are used to treat advanced melanoma and SCC 33. Cemiplimab is another checkpoint inhibitor that may be used for locally advanced BCC and SCC 34.
  • Targeted therapy: BRAF and MEK inhibitors are used for melanomas with specific gene mutations 36. Vismodegib and sonidegib are targeted therapy drugs that inhibit the hedgehog pathway, which is involved in BCC growth 37. Cetuximab targets a specific protein on cancer cells and may be used for SCC 34.
  • Chemotherapy: Chemotherapy drugs, such as dacarbazine and temozolomide, may be used in certain situations for melanoma, such as metastatic disease 38. Cisplatin or 5-fluorouracil (5-FU) may be used for some advanced SCCs 39.

Systemic Therapies in the Pipeline

Research is ongoing to develop new systemic therapies for skin cancer. Clinical trials are investigating novel immunotherapies, targeted therapies, and combination therapies to improve treatment outcomes and reduce side effects. These include:

  • Oncolytic viruses: These viruses are designed to selectively infect and kill cancer cells.
  • Cancer vaccines: These vaccines aim to stimulate the immune system to recognize and destroy cancer cells.
  • Adoptive cell therapy: This therapy involves isolating and modifying a patient’s own immune cells to enhance their ability to fight cancer.

Non-Traditional Therapies

For individuals seeking alternatives to surgery or radiation, several non-traditional therapies are available:

Topical Treatments

Topical treatments, such as creams or gels containing 5-fluorouracil or imiquimod, can be applied directly to the skin to kill cancer cells and stimulate the immune system 40. These treatments offer advantages such as minimal scarring and convenience, but they may cause skin irritation and are not suitable for all types of skin cancer 41.

Cryotherapy

Cryotherapy involves freezing and destroying cancer cells with liquid nitrogen 42. It is often used for smaller, superficial skin cancers. Cryotherapy is a minimally invasive procedure with less pain and bleeding compared to traditional surgery, but it may cause temporary numbness, blistering, or skin discoloration 43.

Photodynamic Therapy (PDT)

PDT uses a combination of a photosensitizing drug and a specific type of light to destroy cancer cells 45. It is often used for superficial BCC and SCC. PDT is less invasive than surgery and has minimal scarring, but it can only treat areas that are accessible to light and may cause temporary light sensitivity 45.

Mohs Surgery

Mohs surgery is a precise surgical technique that involves removing thin layers of skin one at a time while checking for cancer cells in each layer 47. It is often used for skin cancers in cosmetically sensitive areas. Mohs surgery has a high cure rate and preserves healthy tissue, but it is more expensive than traditional excision and may require a longer procedure time 48. However, it can be more cost-effective in the long run due to its high cure rates and reduced need for further treatment 49.

Conclusion

Skin cancer is a significant public health concern, but with early detection and appropriate treatment, most cases can be successfully managed. Public health initiatives should emphasize the importance of sun protection, regular skin self-exams, and prompt medical evaluation of suspicious skin lesions. Healthcare providers should be vigilant in educating patients about skin cancer risk factors and promoting preventive measures, particularly in high-risk populations such as men and individuals with darker skin tones. Ongoing research and advancements in systemic therapies and non-traditional approaches offer hope for improved outcomes and a better quality of life for those affected by skin cancer.

Works cited

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Bobak Pousti
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