Renal cell carcinoma in kidney transplant recipients receiving immunosuppression: A 55-year retrospective single-center study.
Authors: Zeppellini Annalisa , Patelli Giorgio , Ferla Fabio , Pedrani Martino , Pierri Silvia , Calvanese Gabriele , Ciarlo Gabriele , Sala Giuseppe , Gri Nicole , Falcone Valentina , Spina Francesco , Sartore-Bianchi Andrea , De Carlis Luciano Gregorio , Siena Salvatore 
Published: February 2025

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Background:
Immunosuppression, the key post-transplant therapy to prevent organ rejection, is associated with an increased cancer risk. Kidney transplantation is the most frequent solid organ transplant, with renal cell carcinoma (RCC) being the most common urologic cancer in kidney transplant recipients (KTR). While numerous retrospective studies address RCC onset in KTR, they often have limitations, including small sample size, case series design, and lack of annotation regarding pathological features and immunosuppressive regimens adopted.
Methods:
We retrospectively evaluated 2,571 KTR between 1969 and 2024 at Grande Ospedale Metropolitano Niguarda, Milan, Italy. The primary aim was to assess the incidence of RCC after kidney transplantation. Also, we examined pathological features, including tumor histology, grade, stage, and site (native kidney or graft). Time from transplantation to RCC diagnosis and immunosuppressive regimens were assessed. Overall survival (OS) was evaluated using Kaplan-Meier estimates and Cox proportional hazards model.
Results:
RCC was diagnosed in 44 KTR, with an incidence of 1.7% (44/2,571, 95%CI 1.2-2.2). Median age at transplant was 48 years (IQR 38-57), with a median time from transplantation to RCC diagnosis of 9 years (IQR 3-18). RCC was diagnosed mostly in males (34/44, 77.3%) and in native kidney (33/44, 75%). Most cases were localized (42/44 pT1-T2, 95.5%), and all received definitive treatment including surgery (41/42, 97.6%) or radiofrequency (1/42, 2.4%). Stage IV at diagnosis was infrequent (2/44, 4.5%). With a median follow-up time of 7 years (IQR 2-10), RCC relapse after definitive treatment was rare (1/42, 2.4%). Bilateral or multiple tumors were observed in 3/44 patients (6.8%), with papillary histology (pRCC) as the most common subtype (24/47, 51.1%). Most KTR received triple immunosuppressive regimens, typically including steroids (90%), calcineurin inhibitors (86.4%), and mycophenolate (75%). There was no significant difference in clinical-pathological characteristics between patients with clear cell carcinoma (ccRCC) or pRCC. Median OS was 28 years (95%CI 23-NR) after transplantation and 10 years (95%CI 8-NR) after RCC diagnosis.
Conclusions:
This is to our knowledge the largest Italian monocentric case series of RCC arising in KTR. We observed a RCC incidence of 1.7% in this KTR population. The predominance of pRCC in this setting (51%) aligns with findings from previous studies with a higher frequency in KTR compared to the expected proportion in the general population (~10-15%). Despite a generally favorable prognosis, the low incidence of advanced-stage disease at diagnosis underscores the importance of early detection and vigilant surveillance in this high-risk population of KTR.