De Novo Renal Cell Carcinoma in Kidney Transplant Recipients: Incidence, Outcomes, and Therapeutic Challenges

Abstract

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan-Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33-5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC.

Keywords: immunosuppressive therapy; kidney transplantation; oncological outcomes; propensity score matching; renal cell carcinoma.

Figure 1

Kaplan–Meier analysis of overall survival (A) and metastasis-free survival (B) of whole cohort of kidney transplant recipients (KTRs) with de novo renal cell carcinoma. Kaplan–Meier analysis and log-rank testing indicated significant inferior OS in UICC stages ≥ III (blue) compared to UICC stage I (red, p < 0.001) (C). Univariate Cox regression identified acute rejection (HR: 3.48, 95% CI: 1.16–10.44, p = 0.03), older age at RCC (HR: 1.09, 95% CI: 1.03–1.16, p = 0.006), advanced UICC stage III (HR: 6.12, CI: 1.41–26.51, p = 0.02) and IV (HR: 27.79, CI: 5.56–138.83, p < 0.001), higher pT stage (HR: 9.23, 95% CI: 2.21–38.56, p = 0.002), cN1 (HR: 8.74, 95% CI: 2.08–36.68, p = 0.003), M1 (HR: 16.92, 95% CI: 3.90–73.30, p < 0.001), and high-grade tumors (G1/G2 vs. G3, HR: 26.99, 95% CI 2.46–296.07, p = 0.007) as significantly associated with poor overall survival (D). Significant p values are indicated by * p < 0.05.

Figure 2

Propensity matched comparison revealed no significant differences in overall survival (A) and metastasis-free survival (B) between localized renal cell carcinoma patients without kidney graft (red, no KTR) and kidney transplant recipients with localized renal cell carcinoma (blue, KTR) in log-rank testing (p = 0.72 and 0.61).