*Purpose: Due to an improved patient and kidney allograft survival, cancer is increasingly recognized as the major cause of death after kidney transplantation. Cancer risk is increased by two- to four-fold in kidney transplant recipients (KTRs) and tends to be higher than in age-matched individuals from the general population. KTRs with long-term survival of more than 20 years, however, haven’t been studied so far.

*Methods: We followed 294 KTRs with kidney allograft survival of more than 20 years on a quarterly/yearly basis in our kidney transplant outpatient clinic. KTRs were analyzed for the development of cancer, cancer type, cancer-associated risk factors, and patient and kidney allograft outcomes.

*Results: By 10, 20, and 30 years post-transplant KTRs showed an incidence of cancer of 10.4%, 14.6% and 39.9%, and an incidence of non-melanoma skin cancer (NMSC) of 10.3%, 33.5%, and 76.8%. By recipient age of 40, 60, and 80 years KTRs showed an incidence of cancer of 3.4%, 14.5%, and 55.2%, and an incidence of NMSC of 1.7%, 31.6%, and 85.2%. By 30 years post-transplant PTLD showed the highest incidence of 7.3% followed by renal cell carcinoma with 4.3%. Risk factors associated with the development of cancer included recipient age, the time on maintenance immunosuppression, and smoking. Risk factors associated with the development of NMSC included recipient age, the time on maintenance immunosuppression, and the use of thiazide diuretics. KTRs with cancer showed inferior patient survival with 25-year patient survival of 75.2% vs. 85.6%, and 30-year patient survival of 56.1% vs. 66.7%. No differences were observed concerning death-censored kidney allograft survival or the development of donor-specific antibodies (p>0.05).

*Conclusions: With increasing patient and kidney allograft survival, cancer is becoming the major cause of mortality and morbidity, and PTLD remains the most common cancer type even in the very long-term. Emphasis should be placed on adherence to cancer surveillance protocols for early detection and prompt management.

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