INTRODUCTION
Renal cell carcinoma (RCC) constitutes approximately 2-3% of all adult malignancies globally, with an estimated 400,000 new cases diagnosed annually 1,2. Patients with end-stage renal disease (ESRD) face a substantially amplified risk of developing RCC, estimated to be 3-5 times higher than that of the general population 3,4. This elevated risk is attributed to the uremic state, characterized by chronic inflammation, oxidative stress, and immune dysregulation. Consequently, with aging dialysis populations and prolonged exposure to renal replacement therapy, transplant clinicians are increasingly confronted with candidates who have a history of, or present with, incidentally detected RCC.
Historically, any prior diagnosis of RCC was considered a contraindication to kidney transplantation, mandating prolonged, often arbitrary, cancer-free waiting periods. This conservative stance was rooted in concerns that post-transplant immunosuppression would precipitate cancer recurrence. However, accumulating evidence from large registry studies and cohort analyses has fundamentally challenged this dogma. It is now recognized that for patients with localized, low-grade, and completely resected tumors, the risk of post-transplant recurrence is negligible. Therefore, subjecting these individuals to prolonged dialysis may confer unnecessary morbidity and mortality without meaningful oncologic benefit 5,6. This manuscript reviews the contemporary evidence guiding the evaluation, management, and post-transplant care of kidney transplant candidates with a history of RCC, advocating for a risk-stratified approach.
MATERIALS AND METHODS
In July 2025, we performed a narrative literature synthesis to summarize the current state of evidence. A search of PubMed, Embase, and the Cochrane Library was conducted for relevant English-language publications from the past decade (2014-2025). Search terms included combinations of “Kidney Transplantation”, “Renal Transplantation”, “Renal Cell Carcinoma”, “Kidney Cancer”, and “Pretransplant Malignancy”. The reference lists of retrieved articles were also manually screened for additional relevant publications.
We prioritized full-text journal articles, including registry analyses, cohort studies (both prospective and retrospective), and clinical practice guidelines. Case reports, letters, editorials, and abstracts were excluded. Studies focusing solely on de novo RCC arising after transplantation were also excluded. A PRISMA flow chart 7 of the search strategy is shown in Figure 1.
The identified literature was analyzed to extract data on key themes: (1) oncologic outcomes and recurrence risk post-transplantation; (2) recommendations for waitlisting and optimal waiting periods; (3) surgical management strategies in potential transplant candidates; (4) the role of immunosuppression; and (5) post-transplant surveillance protocols. A narrative synthesis of these findings was constructed to provide a comprehensive overview for clinicians.
Full-text articles complying with the inclusion criteria were screened, and the following information was entered into a structured Excel data table: study characteristics (i.e. the first author’s last name, year of publication, country of participating institution, type of study) (Tab. I).
RESULTS
Epidemiology and unique tumor biology in ESRD
The global incidence of RCC shows significant geographical variation, with rates typically ranging from 13-17 and 7-10 per 100,000 in men and women, respectively 2. The risk escalates dramatically in the ESRD population, particularly among individuals with dialysis durations exceeding ten years 3,4. Importantly, RCC arising in the context of ESRD often exhibits distinct histopathological features, with a higher prevalence of papillary and acquired cystic disease-associated subtypes, which are frequently multifocal and demonstrate a more indolent biological behavior compared to sporadic clear cell RCC 11. This difference in tumor biology is a cornerstone of the revised, more permissive approach to transplantation.
Surgical management: balancing oncology and nephrology
The surgical approach to RCC in a potential transplant candidate must be meticulously planned, balancing oncologic radicality with the preservation of renal function:
- Radical nephrectomy: for patients already dependent on dialysis, radical nephrectomy is the procedure of choice. In this context, preserving non-functioning renal parenchyma offers no clinical benefit, and complete removal of the kidney mitigates the risk of multifocal tumor recurrence in the native organs 12,13;
- Nephron-Sparing Surgery (NSS): for patients not yet on dialysis, NSS is the preferred option, particularly for small, localized, and exophytic tumors. This approach preserves native renal function, delays the onset of ESRD, and maintains eligibility for transplantation 12,13.
Histopathological examination of the resected specimen is critical. Confirmation of a low-grade, organ-confined tumor (pT1a) with negative surgical margins (R0 resection) provides the reassurance necessary for safe waitlisting.
Risk-stratified timing for transplantation
The traditional “one-size-fits-all” waiting period of 2-5 years has been superseded by a risk-adapted model 6,8:
- Low-risk RCC (pT1a, ≤ 3-4 cm, low grade): for tumors that meet these criteria, current guidelines from organizations like the European Renal Best Practice suggest that immediate waitlisting is acceptable 9,14. The recurrence risk in this group is exceedingly low (< 2-3%), and the survival benefit of transplantation outweighs the negligible oncologic risk 5,10,15-18;
- Intermediate-risk RCC (pT1b-T2): a waiting period of approximately 2 years of disease-free observation is generally recommended to confirm oncologic stability;
- High-risk RCC (≥ pT3, nodal involvement, high-grade features): a more cautious approach is warranted, typically requiring a minimum of 5 years of documented remission before considering transplantation. Metastatic disease remains an absolute contraindication 19,20.
This stratification is supported by multicenter studies, such as the analysis by Cognard et al., which identified clear cell histology, advanced stage, and high Fuhrman grade as key predictors of recurrence 10.
The dual role of immunosuppression
The choice of immunosuppressive regimen is a critical consideration:
- Calcineurin inhibitors (CNIs): CNIs like tacrolimus and cyclosporine have been implicated in pro-oncogenic pathways, potentially promoting angiogenesis and tumor progression through interactions with VEGF and TGF-β 21;
- mTOR inhibitors: sirolimus and everolimus provide effective immunosuppression while concurrently exerting antiproliferative and antiangiogenic effects by inhibiting the mTOR pathway. Meta-analyses and registry studies have associated mTOR inhibitor-based regimens with a significant reduction in the incidence of post-transplant malignancies, including RCC recurrence 22,23. However, their use must be balanced against a higher incidence of adverse effects (e.g., dyslipidemia, proteinuria, impaired wound healing).
The importance of structured surveillance
These patients must be subjected to surveillance protocols that vary according to their risk profile:
- Low-risk patients: annual abdominal imaging (ultrasound, CT, or MRI) for the first 5 years, potentially transitioning to biennial imaging thereafter;
- High-risk patients: more intensive surveillance with cross-sectional imaging (CT or MRI) every 6 months for the first 2-3 years, followed by annual imaging.
Such dedicated protocols facilitate the early detection of recurrence at a manageable stage, improving survival outcomes 24-26. The overall risk of recurrence in carefully selected patients remains low (< 5% at 5 years), and graft survival is comparable to that of transplant recipients without a cancer history 10.
CONCLUSIONS AND FUTURE DIRECTIONS
Kidney transplantation after curative treatment of RCC is a safe and effective strategy when guided by rigorous risk stratification and multidisciplinary management. For small, organ-confined tumors, mandatory waiting periods are obsolete and may unnecessarily compromise patient survival. The surgical approach must be individualized based on native renal function, and post-transplant care should incorporate tailored immunosuppression and lifelong surveillance.
Future research should focus on prospective, multi-national registries to refine risk prediction. The integration of molecular biomarkers holds promise for distinguishing indolent from aggressive tumors. Furthermore, randomized trials are needed to definitively establish the optimal immunosuppressive strategy that balances graft function with oncologic safety. By embracing this evidence-based, personalized approach, we can ensure that a history of RCC does not unjustly deprive patients of the survival and quality-of-life benefits afforded by kidney transplantation.
Conflict of interest statement
The authors declare no conflict of interest.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author contributions
All authors contributed equally to the conception, design, data collection, analysis, and writing of this manuscript. All authors read and approved the final version of the manuscript.
Ethical considerations
Not applicable.
History
Received: November 22, 2025
Accepted: November 24, 2025
Figures and tables
Figure 1. PRISMA 2009 flow diagram.
| Author | Year | Country | Type of study |
|---|---|---|---|
| Dahle, Skauby 5 | 2021 | Norway | Review |
| Frascà, Brigante 6 | 2018 | Italy | Review |
| Boissier, Hevia 7 | 2018 | France | Review |
| Pascual, Abramowicz 8 | 2014 | Spain | Clinical practice guideline |
| Cognard, Anglicheau 9 | 2017 | France | Retrospective |
