Background and Aim
Solid organ transplant recipients face markedly elevated rates of keratinocyte cancer (KC), yet prior studies have largely characterised KC risk as a single time-averaged measure of cumulative burden. This approach cannot determine whether KC rates are increasing, stable, or decreasing over the post-transplant course. The TOSCANI study aimed to characterise the longitudinal trajectory of KC accumulation and identify its clinical determinants.
Methods
We conducted a prospective observational cohort study of kidney and lung transplant recipients attending two Brisbane transplant centres, with KC surveillance from 2017 to 2024. Annual KC counts were modelled using a mixed-effects negative binomial regression model with time since transplant as a time-varying predictor, yielding incident rate ratios (IRRs) for longitudinal KC trajectory. Patients were additionally classified into burden subgroups using k-means clustering of model-derived random intercepts, with group-based trajectory modelling (GBTM) performed as a secondary validation analysis. An exploratory expanded model incorporated skin phenotype variables.
Results
Across 240 patients (126 kidney, 114 lung), 3,755 KCs were diagnosed over 1,637 person-years of follow-up. Annual KC rate increased by 4.7% for each additional year post-transplant (IRR 1.047, 95% CI 1.031–1.063; p<0.001), independent of age. Each additional year of age was independently associated with a 5.4% higher annual KC rate (IRR 1.054, 95% CI 1.038–1.070; p<0.001). Patients separated into two distinct persistent burden phenotypes: a low-burden group (61%, adjusted KC rate 38% below the cohort mean) and a high-burden group (39%, adjusted KC rate 2.3 times the cohort mean), representing an approximately 3.7-fold difference in adjusted annual KC rate. No modifiable factor predicted high-burden group membership; only older age and longer post-transplant duration were significant. An exploratory analysis identified olive or dark skin colour as independently associated with an 84% reduction in annual KC rate compared with fair skin (IRR 0.158, 95% CI 0.069–0.363; p<0.001).
Conclusions
KC accumulation in transplant recipients follows a consistent upward trajectory driven by age and post-transplant duration, with patients falling into two distinct persistent burden phenotypes. These findings provide longitudinal quantification of KC risk in this population and support ongoing, intensified surveillance in older patients and those with longer transplant duration.