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Kidney Transplantation Kidney CJASNTransplantation ePress. Published on March 29, 2021 as doi: 10.2215/CJN.14570920 Long-Term Management Challenges De Novo Malignancies after Kidney Transplantation David Al-Adra,1 Talal Al-Qaoud,1 Kevin Fowler ,2 and Germaine Wong3,4,5 Abstract Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex- matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. 1Department of Moreimportantly,effectivescreeningandtreatmentstrategiesarelimitedinthishigh-riskpopulation.Inthisreview,webegin Surgery, University with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, of Wisconsin School of education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of Medicine and Public Health, Madison, kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current Wisconsin understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives. 2The Voice of the CJASN 17: ccc–ccc, 2022. doi: https://doi.org/10.2215/CJN.14570920 Patient, Inc., Columbia, Missouri 3Sydney School of Patient’s Voice regarding their awareness of their health risks, including . Public Health, As someone living with a kidney transplant for 16 cancer. Moreover, the survey could also gain insights into University of Sydney, years, this article resonated with me. When my the recipients’ ability to self-manage their health risks. In Sydney, New South nephrologist identified me as a pre-emptive candidate Wales, Australia turn, this information would guide the community in 4 for a kidney transplant, he educated me immediately their patient education and activation efforts. Centre for Kidney Research, Kids on the cardiovascular risks post-transplant. In addi- Research Institute, The tion, he persuaded me to adopt routine exercise into Children’s Hospital my lifestyle as a proactive measure. That recommen- Introduction at Westmead, dation has served me well because I have maintained Kidney transplantation is the best treatment option for Westmead, New South Wales, Australia routine exercise post-kidney transplant. 5 acceptable candidates with kidney failure because it Centre for Transplant I have a sense of control in mitigating my cardio- improves the quality (1) of life and overall survival for and Renal Research, vascular risk. Beyond routine exercise, I have ensured patients on maintenance dialysis (2). It is also the most Westmead Hospital, my BP is within the recommended range. I strive to cost-effective treatment strategy for those needing KRT (3). Westmead, New South Wales, Australia maintain a heart-healthy diet, and my transplant nephrol- However, transplantation is not a cure. Patients ogist prescribed a cholesterol-lowering medication imme- require life-long immunosuppression to maintain Correspondence: diately after my transplant when my metabolic panel was optimal allograft function. One of the most feared Dr. Germaine Wong, out of range. Recently, I scheduled an appointment with complications associated with immunosuppression Sydney School of a preventive cardiologist. That appointment resulted after kidney transplantation is cancer (4). Cancer is Public Health, Faculty in the prescription of a sodium-glucose cotransporter-2 also considered as one of the core clinical outcomes of Medicine and inhibitor to reduce the risk of prediabetes, and a follow- Health, University of by clinicians, patients, and caregivers, and there is Sydney, Camperdown, up appointment for a computed tomography scan. now consensus among key stakeholders suggesting 2006, NSW, Australia. In contrast, my experience with managing cancer cancer should be included as an outcome in all Email: germaine. risks has not been clear. Although the risks of skin interventional trials of kidney transplantation (5). [email protected]. cancer were communicated, I had to ensure the After cardiovascular disease, cancer is the second gov.au guidelines were followed closely. For example, from leading cause of death among recipients of transplants the very beginning, I scheduled quarterly surveillance in most Western countries (6). The higher risks and appointments with my dermatologist. Initially, quar- poorer cancer outcomes have prompted clinicians and terly appointments were discouraged until skin bi- policy makers to adopt preventive policies, such as opsy specimens were positive. Mole mapping was human papillomavirus (HPV) vaccination (7) and initially discouraged until the dermatologists discov- cancer-screening strategies, to detect cancers at their ered irregular moles. Nonetheless, I feel confident earliest possible stage before they progress into now in managing the risk of skin cancers. For my advanced-stage, incurable disease (8). It is also im- other cancer risks, a proactive path remains elusive. perative to understand the mechanistic insights into Because the United States is moving to 3-year outcomes cancer cell development under the influence of im- for transplant metrics, this affords the US transplant munosuppression and devise innovative treatment community to assess the effectiveness of patient educa- strategies for recipients of transplants. This review tion. As a first step, I would like to see the American focuses on the incidence, mechanisms, diagnosis, Society of Transplantation and the American Society of prevention, and treatment of cancer after kidney Nephrology survey recipients of kidney transplants transplantation. www.cjasn.org Vol 17 July, 2022 Copyright © 2022 by the American Society of Nephrology 1 2 CJASN Incidence of All-Cause and Site-Specific Cancer after Risk Factors for Cancer Development Transplantation There are many reasons for the higher cancer risk after The cumulative incidence of solid organ cancer ranges transplantation. Some of these factors, such as increasing between 10% and 15% (6,9–11) at around 15 years after age, male sex, smoking, and prolonged sun exposures, transplantation. For skin cancers, the cumulative incidence are shared by patients in the general population. Other reaches .60% in Europe, Australia, and New Zealand. The risk factors, including immunosuppression use (T cell– excess overall cancer risk in patients with kidney transplant depleting agents), acute rejection (17), sensitization status exceeds that of the general population by approximately two- to (18), and duration of dialysis before transplantation (19), three-fold after adjustment for age and sex. The magnitude of are specific to those with kidney disease and transplant the higher risk is also dependent on cancer types, with the populations. Although long-term immunosuppression is a greatest risk in viral-related and immune-driven cancers such as major contributor to cancer development after transplan- post-transplant lymphoproliferative disease (PTLD), anogenital tation, there is now convincing observational evidence to cancer, and Kaposi sarcoma (12,13). Interestingly, certain solid suggest that having CKD (irrespective of the CKD stage) is organ cancers such as breast and prostate cancers are not associated with higher cancer risk and poor cancer out- increased in recipients of transplants (Figure 1). comes (20,21). Many of these cancers, such as renal cell carcinoma and multiple myeloma, are over-represented in the CKD/kidney-failure populations. Cancer may also de- Cancer Mortality in Recipients of Kidney Transplants velop in recipients of kidney transplants because of impaired Once cancers develop, the risk of death is high. Obser- tumor surveillance and immunity to viral or other tumor vational data in most Western countries have shown the antigens. The observed higher cancer risk is further com- standard mortality ratios for all cancer types are at least pounded in patients who have had a previously treated – 1.8–1.9 times higher compared with the age- and sex- pretransplant malignancy (22 24). Recent studies indicate a matched general population. The risk is greatest among higher incidence of all-cause mortality in recipients of solid those with melanoma, urogenital cancers, and non- organ transplants who have a pretransplant malignancy than Hodgkin lymphoma, with an overall risk of cancer- those without, but the cause of death may not necessarily be – related death exceeding five to ten times that of those driven by cancer recurrence alone (24 26). fi without kidney transplants (Figure 2) (14). The exact The speci c types of cancer that develop after trans- reasons for the higher risk of death are unclear, but may plantation also vary by geographic areas. Observational be due to potential differences in the cancer cell biology in and registry data from Europe, North America, Australia, recipients of transplants resulting from long-term immu- and New Zealand indicate the most common cancer types nosuppression, associated comorbidities, and low uptake of are nonmelanoma skin cancers (NMSCs), PTLD, and lip – recommended prevention and screening strategies (15). cancer (10,27 29). In contrast, data from non-Western Patients are primarily committed to and preoccupied
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