Why transplant medicines raise skin cancer risk, how often skin checks are done, and what is known about prevention and treatment options.
Skin cancer is the most common cancer in people who have received a kidney, liver, heart, or lung. The drugs that protect the new organ are the cause, and they can't simply be stopped. Transplant teams and dermatologists manage this risk together, and an active plan prevents many serious problems.
The immune system does more than fight infection. It patrols the skin, finding and destroying cells that ultraviolet (UV) light has damaged before they grow into cancers. Anti-rejection medicines quiet that patrol so it leaves the transplanted organ alone. Damaged skin cells then have a better chance of surviving and multiplying.
The effect is largest for squamous cell carcinoma (SCC), a cancer of the flat cells in the outer skin. The Skin Cancer Foundation reports that transplant recipients develop SCC about 100 times more often than the general population. Basal cell carcinoma is about 6 times more common, melanoma about 2 times, and Merkel cell carcinoma, a rare and aggressive skin cancer, about 24 times.
Estimates differ between studies. A recent U.S. study from Kaiser Permanente (Lee and colleagues, JAMA Dermatology, 2025) compared 2,083 transplant recipients with matched members who had no transplant and found about 8 times the risk of any skin cancer after transplant. Risk varies a great deal from person to person.
SCCs usually begin to appear 3 to 5 years after the transplant, often as several tumors over time. In transplant recipients, SCC, melanoma, and Merkel cell carcinoma are all more likely to spread than in other people. Early treatment of each new spot matters for that reason.
Risk rises with fair skin, older age at transplant, male sex, a history of heavy sun exposure, and any skin cancer before the transplant. Some centers use a scoring tool called SUNTRAC, which combines these factors to sort patients into risk groups and set how soon the first skin exam should happen.
Most recipients take a combination of drugs, and the total intensity and duration of immune suppression count as much as any single drug. Even so, the drugs are not identical.
The TUMORAPA trial tested a switch directly (Euvrard and colleagues, New England Journal of Medicine, 2012). It enrolled 120 kidney recipients who had already had at least 1 SCC. Over 2 years, new SCCs developed in 22% of those switched to sirolimus and 39% of those who stayed on a calcineurin inhibitor. The switch had costs. Serious side effects were more frequent with sirolimus, and 23% of patients stopped taking it. Transplant doctors weigh a change in anti-rejection medicine against the health of the organ, usually after a patient has had multiple or high-risk skin cancers.
Schedules differ between centers. A common pattern, described by the Skin Cancer Foundation, is a full-body skin exam by a dermatologist once a year for recipients who have never had skin cancer, and every 6 months for those who have had a skin cancer or have extensive sun damage. People who have had several cancers may be seen every 3 to 4 months. Monthly self-checks at home fill the gaps.
Sun protection is the foundation: clothing, hats, shade, and broad-spectrum SPF 30 or higher on exposed skin every day. Dermatologists also treat precancerous rough patches, called actinic keratoses, across whole areas such as the scalp or forearms, using fluorouracil cream, imiquimod cream, or photodynamic therapy.
For people who keep forming SCCs, doctors may prescribe acitretin, a vitamin A-related pill. In a placebo-controlled trial of 44 kidney recipients (Bavinck and colleagues, Journal of Clinical Oncology, 1995), 11% of those taking acitretin developed a new SCC over 6 months, compared with 47% of those on placebo. Dry lips, dry skin, and some hair thinning are common, blood fats can rise, and the benefit fades once the drug is stopped. Acitretin causes birth defects, so doctors avoid it in anyone who could become pregnant.
Nicotinamide, a form of vitamin B3, lowered new skin cancers in a trial of people with normal immune systems. The transplant-specific trial, ONTRANS (Allen and colleagues, New England Journal of Medicine, 2023), found no benefit: 207 new cancers with nicotinamide and 210 with placebo among 158 recipients. The trial closed early and was smaller than planned, so a small benefit can't be ruled out. More data is needed.
Checkpoint inhibitors such as cemiplimab and pembrolizumab are standard treatments for advanced SCC and melanoma. These drugs release the immune system's brakes, which can also trigger an attack on the transplanted organ. A review of 119 published cases (Portuguese and colleagues, Journal of the National Comprehensive Cancer Network, 2022) found organ rejection in about 41% of transplant recipients treated with these drugs and loss of the organ in about 24%. About 68% of the advanced skin SCCs in that review shrank in response.
Oncologists and transplant teams make these decisions jointly, and clinical trials are testing adjusted anti-rejection regimens that may protect the organ during immunotherapy.
