*Purpose: Transplantation of a kidney (KTA), pancreas (PTA), or a simultaneous pancreas-kidney (SPK) in a patient with end-stage organ failure is a lifesaving treatment. Patient and graft survival improved significantly over time due to more effective immunosuppressive agents; however, their long-term use increases the likelihood for developing posttransplant malignancies. This study analyzed the incidence of de-novo malignancies in diabetic patients after organ transplantation.

*Methods: All primary technically successful primary pancreas and/or kidney transplants performed between 2005 and 2019 were included. Pancreas after kidney transplants were excluded: (1) the pancreas is a retransplant and (2) the time interval between the 2 transplants can be long. De-novo primary malignancies reported to UNOS/OPTN or reported as cause of graft loss or death were used. Patients with previous malignancies, lymphoproliferative disease, or donor-related malignancies were excluded. To provide comparable age distribution between KTA and SPK and PTA, all pancreas transplants were matched by age, gender, and transplant year with KTA in diabetic patients only. The Kaplan Meier Method was used to estimate the rate of malignancy over time. Descriptive statistics were performed and a multivariable risk model for the development of de-novo malignancies was developed.

*Results: In 22,721 transplants (11,364 KTA, 1,013 PTA, 10,344 SPK) a total of 1,122 primary malignancies were diagnosed over time. Figure 1 shows the development in the 3 categories. At 5- (10-) years the cancer rate was 3.1% (8.3%) in KTA, 3.6% (10.4%) in SPK, and 5.3% (13.7%) in PTA (p<0.0001). Table 1 list the frequencies of the most frequently reported malignancies. Differences in the frequency between pancreas and kidney transplants were found for squamous/basal skin cancers (PTA, SPK > KTA) and cancers of the genitourinary system (KTA > SPK, PTA). Risk factor analysis identified older age and white race as the most influential risk factors followed by induction therapy with depleting antibodies.

*Conclusions: In general, organ transplant recipients are at a greater risk for developing malignancies. Type and frequency of specific cancers vary between kidney and pancreas transplant recipients: Differences in type and frequency between pancreas and kidney transplants were found for squamous/basal skin cancers (PTA, SPK > KTA) and cancers of the genitourinary system (KTA > SPK, PTA). Long-term use of immunosuppression requires awareness for the development of malignancies and lifelong surveillance.

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