The patient had an advanced cutaneous squamous cell carcinoma (cSCC) on the face that seemed to be affecting the facial nerve, ruling out aggressive surgery. When Mohs surgery failed to clear the tumor, radiation was ordered. But the best option — an immune checkpoint inhibitor — could not be administered because the patient was a lung transplant recipient.
Although approved for metastatic cSCC, immune checkpoint inhibitors are associated with a higher potential for rejection of an organ transplant.
“The feeling is that the risk of rejection is just too great if we were to try to give an immune checkpoint inhibitor,” said Sean Christensen, MD, PhD, director of dermatologic surgery at Yale Dermatology–Branford, in Connecticut, who was treating the patient. Dr. Christensen consulted with the transplant team, and together they decided to switch the patient to sirolimus, an immunosuppressant that has been shown to have less risk of promoting skin cancer in those who take the medication. Sirolimus, however, is not as well tolerated as the usual first-line immunosuppressant, tacrolimus.
Dr. Christensen
Dr, Sean Christensen
Organ transplant recipients have a 200-fold increased incidence of keratinocyte carcinoma compared with immunocompetent individuals, and cSCC accounts for 80% of skin cancers in those recipients, according to a 2022 paper published in Transplant International, by Matthew Bottomley, MRCP, and colleagues at the University of Oxford, England.
And in a 2017 JAMA Dermatology study on skin cancer in organ transplant recipients in the United States, Sarah Arron, MD, and colleagues, wrote that posttransplant cSCC has an incidence of 812 per 100,000 person-years. To put that in perspective, breast cancer has an incidence of 126 per 100,000 person-years and prostate cancer, an incidence of 112 per 100,000 person-years, according to data from the Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention, respectively.
Once a transplant recipient has a single cSCC, he or she is at higher risk for developing multiple lesions and is at greatly increased risk for metastasis and death. Skin cancer-specific mortality in transplants patients is ninefold higher than for immunocompetent patients, reported Johns Hopkins dermatologist Kristin Page Bibee, MD, PhD, and colleagues in a 2020 paper in Oral Oncology.
Clinicians focus primarily on reducing patients’ sun exposure to prevent precancerous and cancerous lesions. While field therapy, such as topical 5-flourouracil, and systemic therapy, including acitretin, can be as effective in treating cSCCs as they are for immunocompetent patients, dermatologists are hoping for more tools.
Dr. Christensen, associate professor of dermatology, Yale University, told this news organization that immune checkpoint inhibitors might become more useful in the future as trials are exploring the feasibility of injecting them directly into the cancers. “That’s a really exciting area of research,” he said, noting that direct injection would lower the risk of transplant rejection.
In an interview, Dr. Bottomley said that he is excited about new techniques, such as high-resolution spatial transcriptomic and proteomic profiling. Those techniques will allow researchers “to identify new pathways and mechanisms that we can target to reduce cSCC risk in both immunocompetent and immunosuppressed patients, ideally without the increased risk of graft rejection that we see with immune checkpoint inhibitors,” said Dr. Bottomley, a consultant nephrologist in the Oxford Kidney and Transplant Unit at Churchill Hospital.
Dr. Bottomley
Dr. Matthew Bottomley