Three MOHs Procedures and Over a Dozen Skin Biopsies Later: My Perspective
Prologue
When I was asked to provide commentary on this article, I jumped at the opportunity. Since I had my third Mohs procedure two months ago, the subject is a very personal one to me. Moreover, the topic is also timely professionally. On September 27 and 28, 2018, I participated on behalf of the Kidney Health Initiative (KHI) in the Food and Drug Administration (FDA) Workshop, Evidence Based Treatment Decisions: The Right Dose and Regimen—the Right Patient/Individualized Treatment. The FDA and the American Society of Transplantation are determining a new regulatory pathway for transplant medications; a shift to precision medicine in transplantation.
As someone living with a kidney transplant for over 14 years, I have learned the value of developing a risk mitigation strategy. Beyond the basics such as routine lab monitoring, colonoscopy screenings, and prostate testing, I have searched for ways to preserve the health of my kidney transplant, and reduce health risks. For example, at the direction of my transplant nephrologist and dermatologist, this year I started oral nicotinamide to prevent the development of skin cancers.
While the risk of cancer was downplayed before my transplant, the scientific evidence reveals a different reality. In 2016 Dr. Sergio Acuna, et al. published in JAMA Oncology “Cancer Mortality Among Recipients of Solid-Organ Transplantation in Ontario, Canada.” In a retrospective study of over 11,000 Solid Organ Transplant Recipients (SOTRs), cancer death rates were compared with the expected rate in Ontario. The largest increase in cancers occurred with non-melanoma skin cancer (NMSC), liver/biliary, and Non-Hodgkin Lymphoma. Because of the cancer risk experienced by SOTRs, I would like to thank the TUMORAPA Study group for conducting this chemoprevention trial.
Trial Design
The five year sirolimus study is a follow up to the TUMORAPA study. In this chemoprevention trial, 43 transplant recipients were assigned to the sirolimus arm, and 45 were assigned to calcineurin inhibitors (CNIs). In that 2-year study, switching from calcineurin inhibitors to sirolimus had an antitumor effect among kidney-transplant recipients with previous squamous-cell carcinoma. The TUMORAPA study was extended to a five-year trial with 28 patients completing the sirolimus arm and 25 completing the CNI study arm.
Study Results
Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group than in the CNI group. When patients were studied in subgroups, this result remained significant only for patients with one cutaneous squamous cell carcinoma.
Regarding kidney function, no episodes of acute rejection occurred and mean serum creatinine function remained stable for both study groups.
There was no observed difference in the rate of internal cancers as had been suggested in previous studies with sirolimus.
Discussion
This study demonstrated the value of utilizing sirolimus in kidney transplant recipients who have had previous squamous cell carcinoma to reduce the risk of recurrent skin cancers.
Because of the increased risks of internal cancers that are associated with squamous cell carcinomas, I was disappointed that sirolimus did not reduce the risk of internal cancers.
The reduction in squamous cell carcinoma has to be balanced with the low mortality (3%) in non-melanoma skin cancers that were reported in the JAMA study. One can infer that surveillance and effective treatment by dermatologists are to thank for the low mortality rate. In addition, sirolimus conversion strategies have to be balanced with tacrolimus ability to reduce acute rejection, prevent proteinuria or the development of donor specific antibodies.
“As someone with 14 years of stable kidney function, I am not willing to assume the risk of converting to sirolimus without a reduction in the risk of internal cancers.”
Recommendations
If the studies have not been initiated, I would like to see future combination clinical trials of tacrolimus and sirolimus, and tacrolimus and belatacept. Tacrolimus is the gold standard for reducing acute rejection. It may offer value in patient care by reducing acute rejection the first year, and then gradually adjusting the dose until it is no longer a part of the regimen.
I would like to see sirolimus studied in its ability to reduce internal cancers such as lung, liver, and Non-Hodgkin Lymphoma. These cancers are associated with higher mortality compared to skin cancers.
Since current transplant medications have a high side effect burden, I would like to see pharmaceutical companies include surveillance monitoring tests in future trials. The inclusion of monitoring tests may reduce the side effect burden.