Nicotinamide in the prevention of cutaneous squamous cell carcinoma

 

Skin cancer prevention

When should I use nicotinamide to prevent new cutaneous squamous cell carcinomas?

In patients with several previous skin cancers, nicotinamide may be used as an additional measure to reduce the development of new tumours. It does not replace photoprotection, treatment of actinic keratoses or dermatological follow-up.

Practical answer. Oral nicotinamide 500 mg every 12 hours may be offered to immunocompetent patients with a history of two or more cutaneous squamous cell carcinomas. The benefit is maintained while treatment is continued. I would not routinely recommend it in solid-organ transplant recipients.

Who is a good candidate?

The best-studied profile is a patient who is:

Immunocompetent

The strongest evidence comes from patients without immunosuppression.

Has previous tumours

Particularly if they have had two or more cutaneous squamous cell carcinomas in recent years.

Has persistent risk

Extensive photodamage, numerous actinic keratoses or repeated development of new carcinomas.

This is not primary prevention. There is insufficient evidence to recommend it generally to anyone with photodamage or isolated actinic keratoses who has never had skin cancer.

What benefit can I explain?

In the ONTRAC trial, 386 high-risk patients received nicotinamide 500 mg every 12 hours or placebo for 12 months. Nicotinamide reduced the development of new cutaneous squamous cell carcinomas by approximately 30%.

The important nuance: the effect disappeared after treatment was stopped. It should therefore not be presented as a one-year intervention that provides permanent protection.

How do I use it in practice?

1. Confirm the risk profile: an immunocompetent patient with two or more previous cutaneous squamous cell carcinomas.
2. Maintain the basic measures: photoprotection, self-examination, follow-up visits and treatment of actinic keratoses and early carcinomas.
3. Prescribe nicotinamide 500 mg every 12 hours. The studied regimen lasted 12 months.
4. Review tolerability and adherence. The benefit depends on the patient continuing treatment.

Safety

It is generally well tolerated. The most common adverse effects are gastrointestinal and usually improve after dose reduction or discontinuation.

Laboratory tests

At the dose used for chemoprevention, specific laboratory monitoring is not usually required.

Duration

The main evidence covers 12 months. The optimal duration beyond this period is not well defined.

What about transplant recipients?

In solid-organ transplant recipients, the ONTRANS trial included 158 patients and found no reduction in new keratinocyte cancers, cutaneous squamous cell carcinomas, basal cell carcinomas or actinic keratoses with nicotinamide 500 mg every 12 hours for 12 months.

Practical conclusion: do not use nicotinamide as a standard chemoprevention strategy in transplant recipients. The lack of recommendation is mainly due to the absence of a demonstrated clinical benefit, rather than major toxicity concerns.

Pocket algorithm

Situation	Practical approach
Immunocompetent patient with 2 or more previous carcinomas	Consider nicotinamide 500 mg every 12 hours as an additional measure.
Photodamage or actinic keratoses only, with no previous skin cancer	Do not recommend it routinely.
Solid-organ transplant recipient	Do not use it routinely; prioritise specialist follow-up and other preventive strategies.
Patient who stops treatment	Explain that the preventive benefit is not maintained after discontinuation.

Knowledge gaps

• The optimal treatment duration beyond 12 months is not well established.
• It has not been shown to reduce aggressive cutaneous squamous cell carcinomas, metastases or mortality.
• In transplant recipients, the data are conflicting and further trials are needed.

Take-home message

Nicotinamide 500 mg every 12 hours is a simple and well-tolerated option for secondary prevention in immunocompetent patients with two or more previous cutaneous squamous cell carcinomas. It may reduce the development of new cutaneous squamous cell carcinomas while treatment is continued. It does not replace standard preventive measures and should not be used routinely in transplant recipients.

Main sources

1. Chen AC et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015;373:1618-1626. Open.
2. Allen NC et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. N Engl J Med. 2023;388:804-812. Open.
3. Stratigos AJ et al. European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention — Update 2026. Eur J Cancer. 2026. doi:10.1016/j.ejca.2026.116763.

Content intended for healthcare professionals. Individualise the indication and always maintain photoprotection, treatment of precursor lesions and clinical follow-up.