Battista Lanzillotta

Objectives: Upper urinary tract urothelial cell carcinoma (UTUC) in kidney transplant recipients (KTRs) presents distinct clinical challenges due to the complexities of managing both cancer and the long-term immunosuppressive therapy required to preserve graft function. UTUC in this population often presents at advanced stages, contributing to poorer outcomes compared to immunocompetent individuals. Methods: This systematic review (SR) evaluates the incidence, clinical presentation, treatment approaches, and survival outcomes of UTUC in KTRs, based on 16 retrospective studies including 526 patients. Results: The present study highlights a predominance of female patients (ranging from 50% to 91.6%) and significant variability in time to diagnosis (from 7 to 181 months post-transplant). Tumor characteristics also showed considerable heterogeneity, with high-grade and advanced-stage (T3–T4) tumors being more common. The standard treatment for UTUC in KTRs remains radical nephroureterectomy (RNU), with additional resection of the bladder (TURB) when bladder cancer (BC) coexists. Survival outcomes vary significantly, with 5-year overall survival (OS) rates ranging from 16.7% to 90.9%, strongly influenced by tumor stage at diagnosis. This SR further reports high rates of bladder recurrence (18.8% to 61.2%) and challenges in balancing effective cancer treatment with graft preservation. The variability in immunosuppressive regimens across studies complicates the assessment of their role in UTUC progression. The limitations of the current evidence include small sample sizes, retrospective designs, and inconsistent follow-up durations. Conclusions: This SR underscores the need for tailored treatment strategies and improved long-term surveillance. Future research should focus on prospective studies with larger cohorts, exploring the impact of immunosuppression and novel therapies on UTUC outcomes in KTRs.