Most skin cancers are not melanoma. Basal cell carcinoma and squamous cell carcinoma are the most common cancers of all, and most are cured with simple treatment. A smaller number grow deeply, return after treatment or spread, and Merkel cell carcinoma, a rare skin cancer, can be aggressive from the start. Treatment for these advanced skin cancers changed in 2025, when immunotherapy after surgery was approved for high-risk squamous cell carcinoma. This article explains the three main types, the treatment at each stage, the European research, and the natural compounds studied for skin cancer. Our article on melanoma treatment covers melanoma separately.
Basal Cell Carcinoma
Basal cell carcinoma is the most common cancer in people. It grows slowly and almost never spreads, but if neglected it can invade deeply into the face and surrounding tissue.
Early basal cell carcinoma is treated by removing it surgically, often with Mohs surgery, which removes the cancer layer by layer while sparing healthy skin. Thin, superficial cancers can be treated with creams such as imiquimod or 5-fluorouracil, or with photodynamic therapy, in which a cream makes the cancer cells sensitive to light and a light then destroys them.
Advanced basal cell carcinoma that cannot be removed or has spread is driven by the Hedgehog signaling pathway in almost every case. Pills that block it, Erivedge (vismodegib) and Odomzo (sonidegib), can shrink these cancers. When they stop working or cannot be tolerated, the immunotherapy Libtayo (cemiplimab) is approved.
Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma is the second most common skin cancer. Most are cured by surgery. Higher-risk cancers are larger or deeper, grow along nerves, appear in people with weakened immune systems such as organ transplant recipients, or have spread to lymph nodes.
Immunotherapy after surgery: the 2025 approval. In the C-POST trial, led by Professor Danny Rischin of the Peter MacCallum Cancer Centre in Melbourne, 415 people with high-risk squamous cell carcinoma who had already had surgery and radiation received Libtayo or a placebo. Two years later, 87 percent of those on Libtayo were free of cancer compared with 64 percent on placebo, a 68 percent reduction in the risk of recurrence or death.1 The FDA approved Libtayo for this use in October 2025, and European approval was recommended the same month.
Advanced squamous cell carcinoma. Libtayo and Keytruda (pembrolizumab) are approved for squamous cell carcinoma that cannot be removed or has spread, and immunotherapy given before surgery is being studied to shrink large cancers and spare tissue. People who have had an organ transplant need special care with immunotherapy because of the risk of rejection.
Merkel Cell Carcinoma
Merkel cell carcinoma is rare and aggressive, usually appearing as a fast-growing, painless firm bump on sun-exposed skin in older adults. Most cases are linked to a common virus, the Merkel cell polyomavirus, and the rest to sun damage. Because these cancers are highly visible to the immune system, immunotherapy works well. Bavencio (avelumab), Keytruda and Zynyz (retifanlimab) are approved for advanced Merkel cell carcinoma.
The German ADMEC-O trial. At 20 university centers in Germany and the Netherlands, 179 people whose Merkel cell carcinoma had been completely removed received a year of the immunotherapy Opdivo (nivolumab) or regular observation. Two years later, 84 percent of those given Opdivo were free of cancer compared with 73 percent of those observed. The difference was not yet statistically definitive, and larger trials are under way.2
Precancers and Photodynamic Therapy From Denmark
Actinic keratoses are rough, scaly sun-damage spots that can turn into squamous cell carcinoma. Treating them, and the sun-damaged skin around them, lowers that risk. Researchers at Bispebjerg Hospital in Copenhagen developed daylight photodynamic therapy, in which the light-sensitizing cream is activated by ordinary daylight instead of a lamp. In their randomized study it worked as well as conventional photodynamic therapy and was much less painful.3 It is now widely used across Europe.
Natural Compounds Studied for Skin Cancer
Nicotinamide (vitamin B3), from Australia. In the ONTRAC trial at the University of Sydney, 386 people who had had at least two non-melanoma skin cancers took 500 mg of nicotinamide twice daily or a placebo for a year. Those taking nicotinamide developed 23 percent fewer new basal and squamous cell carcinomas.4 Nicotinamide helps skin cells repair sun damage to their DNA and reduces the suppression of the skin’s immune defenses by sunlight. A later trial in organ transplant recipients did not show the same benefit.
Polypodium leucotomos fern extract, from Italy and Spain. This extract from a tropical fern, studied extensively by Spanish researchers, reduces sun damage to skin cells when taken by mouth. In an Italian study at the University of Chieti-Pescara, 34 men with actinic keratoses on the scalp were treated with photodynamic therapy, and half then took the extract. Those taking the extract had a higher clearance rate and fewer recurrences six months later.5
Other natural compounds may also be beneficial, and our guide to natural compounds and cancer covers many of them. Sun protection remains the foundation of preventing new skin cancers.
The right treatment depends on the type of skin cancer, its size and depth, where it is on the body, and the person’s immune system and other treatments. In a consultation, Dr. Silver, MD, educates you on these options, including the integrative options, and the research behind each one.
How Cancer Expert MD Helps
Cancer Expert MD provides education and consultation for people with every type and stage of cancer, and specializes in Stage IV and metastatic cancer. Our book, The New Reality of Cancer, covers immunotherapy and integrative care in depth. See also our articles on how immunotherapy works and our guide to cancer treatment by type.
Frequently Asked Questions
What are the main types of skin cancer?
Basal cell carcinoma, squamous cell carcinoma and melanoma are the most common. Merkel cell carcinoma is rare but aggressive.
Can basal cell carcinoma spread?
It almost never spreads to distant organs, but if left untreated it can grow deeply into nearby tissue. Pills that block the Hedgehog pathway and immunotherapy treat advanced cases.
What is new for squamous cell skin cancer?
In October 2025 the FDA approved the immunotherapy Libtayo after surgery and radiation for high-risk squamous cell carcinoma, based on a trial that cut the risk of recurrence or death by 68 percent.
Does nicotinamide prevent skin cancer?
In an Australian randomized trial of people with previous skin cancers, it lowered new non-melanoma skin cancers by 23 percent over a year. A trial in organ transplant recipients did not show the same benefit.
About the author. Dr. Silver, MD, graduated from Temple University School of Medicine, completed fellowship training in cardiology, and has practiced medicine for nearly fifty years. A lymphoma survivor of about twenty-five years, he is co-author, with Dr. Lindmeier, DHSc, of The New Reality of Cancer: The Science of Recovery. Read more about Dr. Silver, MD.
Research by Dr. Lindmeier, DHSc, cancer educator and co-author of The New Reality of Cancer.
This article is for general education only and is not individual medical advice. Always consult your own doctor before making any changes to your care.
© 2026 Lovely LYF LLC. All rights reserved. This article draws on the research in The New Reality of Cancer and may not be copied, republished or distributed without written permission.
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Explore our guides: Stage 4 Cancer Options · Advanced Cancer Testing · Integrative Cancer Treatment Options · Natural Compounds and Cancer · Repurposed Drugs for Cancer · Cancer Treatment by Type
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References
- Rischin D, Porceddu S, Day F, et al. Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma (C-POST). New England Journal of Medicine. Published online May 31, 2025.
- Becker JC, Ugurel S, Leiter U, et al. Adjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial. Lancet. 2023;402(10404):798–808.
- Wiegell SR, Haedersdal M, Philipsen PA, et al. Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses: a randomized, controlled, single-blinded study. British Journal of Dermatology. 2008;158(4):740–746.
- Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention (ONTRAC). New England Journal of Medicine. 2015;373(17):1618–1626.
- Auriemma M, Di Nicola M, Gonzalez S, et al. Polypodium leucotomos supplementation in the treatment of scalp actinic keratosis: could it improve the efficacy of photodynamic therapy? Dermatologic Surgery. 2015;41(8):898–902.
This article is for education only. It is not medical advice and does not diagnose or treat any condition. Cancer Expert MD has no financial relationship with any laboratory, drug maker, supplement company, clinic or hospital.
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