Objective: To analyze immunosuppression regimens, demographic characteristics such as race, and donor features across solid organ transplant (SOT) recipients to provide better insight into their effect on the increased cancer risk in SOT. Patients and Methods: We analyzed the Scientific Registry of Transplant Recipients database comprising 534,472 SOT recipients across the United States from October 1, 1987, through March 31, 2015. Results: In total, 53,783 de novo malignancies were identified. Overall 15-year incidence of malignancies was 13.2% (95% CI, 13.0%-13.4%) for kidney ± pancreas, 17.9% (95% CI, 15.9%-19.8%) for pancreas alone, 15.2% (95% CI, 14.9%-15.5%) for liver, 28.1% (95% CI, 27.5%-28.7%) for heart, and 25.6% (95% CI, 24.8%-26.3%) for lung recipients. Relative to kidney ± pancreas transplant, other SOT recipients (except liver) experienced higher risk. On multivariable analysis, use of 2 or more immunosuppressant agents (P<.001), older age (P<.001), male sex (P<.001), white race (P<.001), previous malignancy (P<.001), older donor age (P=.003), and white donor race (P=.03) increased de novo malignancy, whereas mammalian target of rapamycin inhibitor use decreased risk (P=.01), driven by a reduction in skin cancer. Conclusion: Malignancy risk varies across SOT groups and correlates with the number of immunosuppressant drugs used. Mammalian target of rapamycin inhibitor–based immunosuppression seems protective against nonmelanoma skin cancer only. Cancer risk may be improved by minimizing the number of immunosuppressants and the degree of immunosuppression used, particularly in at-risk patients. Increased age, male sex, previous malignancy, and white race are characteristics that should prompt heightened vigilance in cancer screening by transplant physicians and internists who follow this patient population.
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