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How to Manage Renal Masses in Kidney Transplant Recipients? a Collaborative Review by the EAU-YAU Kidney Transplantation and Renal Cancer Working Groups - Beyond the Abstract

Renal masses are frequently diagnosed in the native kidneys of patients with end-stage renal disease (ESRD), due to acquired cystic kidney disease and long-term dialysis, which exposes the renal parenchyma to uremic toxins, promoting chronic inflammation and DNA repair mechanisms impairment. Therefore, during the preoperative assessment, kidney transplant (KT) candidates are screened for any potential malignancy, as they have a four-times higher risk of de novo or recurring malignancies compared to the general population, in the context of life-long triple immunosuppression therapy. However, the literature is highly heterogenous in terms of screening and treatment strategies for these patients, without reaching a consensus regarding the balance between oncological outcomes and graft survival.

We aimed to elaborate a narrative review that explores the current management of the native kidney masses in KT patients.

When it comes to screening strategies, the European Association of Urology (EAU) Guidelines recommend yearly screening for high-risk patients, while other authors advise for biennial check-ups for patients with renal cysts and every 5 years for those without cystic degeneration. Ultrasound is considered the most feasible and cost-effective. If a suspect lesion is detected or an increase in size is reported, computed tomography (CT) or magnetic resonance imaging (MRI) must be performed.

Localized disease benefits from a wide range of treatment options. Active surveillance has been proposed in the management of renal masses in KT recipients, especially in frail patients, with multiple comorbidities and renal masses below 3 cm or imaging suggestive for simple cysts, thus reducing the overall morbidity associated with general anesthesia and surgical intervention. Nephron-sparing and thermoablation techniques are not recommended in malignancies of the native kidneys, as it does not offer any functional advantage and increases the risk of positive surgical margins in immunocompromised patients, which harbor worse oncological outcomes. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, considering the multifocal nature. Aside from autosomal-dominant polycystic kidney disease (ADPKD) cases, minimally invasive radical nephrectomy is advised whenever possible, significantly reducing perioperative complication rates (73% versus 20% for the open versus minimally invasive approach) and providing lower morbidity and shorter length of hospital stay (12 versus 5 days). When it comes to immunosuppression regimes, it has been suggested that patients with localized disease and successful radical nephrectomy do not require immunosuppression dose adjustment. For patients undergoing active surveillance protocols, calcineurin inhibitors should be avoided or replaced, as they stimulate the production of tumorigenesis signaling molecules, thus promoting cancer growth and spreading.

Metastatic disease requires a different approach compared to the general population, as first line systemic therapy based on immune checkpoint inhibitors promotes acute graft rejection by stimulating T cells’ activity. In these cases, mTOR inhibitors seem a viable option, offering a reduced risk of overall malignancy development (HR: 0.68, 95% CI: 0.48-0.95, p = 0.02), as well as other urological cancers (HR: 0.60, 95% CI: 0.36-0.99, p = 0.02). In terms of surgical management, cytoreductive nephrectomy did not highlight a clear benefit, while graftectomy should be performed as a last resort option, to cease immunosuppressant therapy and begin checkpoint inhibitors treatment.

To summarize, post-transplant renal cancer of the native kidneys is a frequent occurrence, most authors advising radical nephrectomy in case of localized disease. For metastatic tumors, cessation of calcineurin inhibitors and mTOR inhibitor replacement satisfies both oncological and immunosuppressive targets. To our knowledge, a standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Written by: Iulia Andras,1 Teodora Telecan,2 Angelo Territo3 and Riccardo Campi4

  1. Servicio de Urología, Universidad de Medicina y Farmacia «Iuliu Hatieganu», Hospital Municipal Cluj-Napoca, Cluj-Napoca, Romania.
  2. Unidad de Cirugía Robótica Urológica y Trasplante Renal, Universidad de Florencia, Hospital de Careggi, Florencia, Italy; Grupo de Trasplante Renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU), Arnhem, The Netherlands.
  3. Grupo de Trasplante Renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU), Arnhem, The Netherlands; Servicio de Urología, Fundació Puigvert, Universidad Autónoma de Barcelona, Barcelona, Spain.
  4. Unidad de Cirugía Robótica Urológica y Trasplante Renal, Universidad de Florencia, Hospital de Careggi, Florencia, Italy; Grupo de trabajo de Cáncer Renal de la sección de Jóvenes Urólogos Académicos (YAU) de la Asociación Europea de Urología (EAU), Arnhem, The Netherlands; Departamento de Medicina Experimental y Clínica, Universidad de Florencia, Florencia, Italy.

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