Long-Term Cancer Incidence Trends in US Kidney Transplant Recipients (1995-2020)

Background: Kidney transplant recipients face significantly elevated cancer risk due to chronic immunosuppression, yet temporal trends in cancer incidence across the modern transplant era remain incompletely characterized. Understanding how cancer risk has evolved with advances in immunosuppressive protocols is essential for optimizing post-transplant surveillance strategies. Purpose: This retrospective cohort study examined long-term trends in cancer incidence among United States kidney transplant recipients from 1995 to 2020, evaluating changes across three distinct immunosuppression eras and identifying demographic and clinical predictors of post-transplant malignancy. Methods: Using data from the Scientific Registry of Transplant Recipients (SRTR) and linked cancer registries, we analyzed 420,814 adult kidney transplant recipients across three eras: Era 1 (1995-2003), Era 2 (2004-2010), and Era 3 (2011-2020). Cancer incidence rates were calculated as events per 1,000 person-years, standardized incidence ratios (SIRs) compared transplant recipients to the general population, and multivariable Cox proportional hazards regression identified risk factors. Results: Overall cancer incidence declined significantly from 18.5 per 1,000 person-years in Era 1 to 15.8 per 1,000 person-years in Era 3, representing a 14.6% reduction (p < .001). Post-transplant lymphoproliferative disorder decreased by 38% and Kaposi sarcoma by 64%. Conversely, non-melanoma skin cancer increased by 9.5%. In adjusted analyses, age was the strongest predictor (hazard ratio [HR] = 6.23, 95% CI [5.58-6.94] for age ≥65 vs. 18-34 years), males had elevated risk (HR = 1.32), and minority recipients demonstrated lower risk than White recipients. Modern era transplantation was independently protective (HR = 0.85, 95% CI [0.81-0.89] for Era 3 vs. Era 1). Conclusions: Cancer incidence among kidney transplant recipients has declined substantially over the past 25 years, likely reflecting improvements in immunosuppression minimization, viral monitoring, and recipient selection. However, persistent elevation in skin cancer incidence underscores the need for continued dermatologic surveillance. These findings support era-specific risk stratification for post-transplant cancer screening protocols. Keywords: kidney transplantation, cancer incidence, post-transplant malignancy, immunosuppression, PTLD, non-melanoma skin cancer, standardized incidence ratio, transplant outcomes