What is the management approach for cancer transmission via kidney transplant?

Management of Cancer Transmission via Kidney Transplant

The management of cancer transmission via kidney transplant requires mandatory screening of all deceased and living potential donors for malignancies, followed by a structured approach to diagnosis and treatment when transmission occurs, with reduction of immunosuppression being the primary intervention strategy.1

Epidemiology and Risk Assessment

• Cancer transmission from donors is rare, with an estimated rate of 1-2 cases per 10,000 organ transplant recipients, though these figures may underrepresent actual incidence due to reporting bias 1
• Transmission risk varies by cancer type, ranging from less than 0.1% for non-invasive in situ cancers to more than 10% for malignant cancers such as melanomas 1
• The median time from transplantation to cancer diagnosis is approximately 8 months (interquartile range 3-13 months), though this varies by cancer type 1
• Recipients with transmitted lung cancers and melanomas have the worst prognosis, with fewer than 50% surviving 2 years after diagnosis 1, 2
• Recipients with transmitted renal cancers have better outcomes, with over 70% surviving at least 24 months after transplantation 2

Prevention Strategies

Donor Screening Requirements

• It is mandatory that all deceased and living potential donors undergo comprehensive screening for transmissible diseases including malignancies 1
• Multiple organizations have developed policies for donor screening, including:
  • Organ Procurement and Transplantation Network/United Network for Organ Sharing
  • British Transplantation Society
  • European Directorate for the Quality of Medicines and Health Care
  • Transplantation Society of Australia and New Zealand 1
• Despite these recommendations, variations in practice exist across transplant centers 1

Risk Communication and Shared Decision-Making

• Patients should be well-informed about the projected risk of disease transmission with higher-risk donors relative to the risk of premature death on dialysis 1
• A structured, personalized, shared decision-making approach should be implemented to improve the value of care to potential transplant recipients 1
• Given the annual death rate of approximately 5% on the kidney transplant waitlist, maximizing the utilization of available donor organs remains imperative 1

Management of Transmitted Cancer

Diagnosis and Monitoring

• Vigilant post-transplant monitoring is essential, particularly during the first year when most transmitted cancers are diagnosed 1
• The diagnosis of donor-transmitted cancer should be suspected when a recipient develops cancer within the first two years post-transplant, especially if the cancer type is unusual for the recipient's age or risk factors 2

Treatment Approach

• Reduction of overall immunosuppression is the primary intervention strategy for transplant recipients diagnosed with cancer 1, 3
• Mammalian target of rapamycin inhibitors (sirolimus and everolimus) may have a promising role in managing cancer after transplantation due to their simultaneous immunosuppressive and anticancer effects 1, 3
• Treatment is generally less effective in transplant recipients than in the general population, requiring careful balance between cancer therapy and graft preservation 1, 4
• Management requires a multidisciplinary approach involving nephrology, hematology/oncology, and transplant specialists, as well as pharmacists 1

Special Considerations for Immunotherapy

• New targeted anti-cancer therapies including checkpoint inhibitors have shown greater efficacy than standard cytotoxic therapies in the general population 1
• However, the use of anti-PD1, cytotoxic T-lymphocyte–associated antigen 4, and other immune modulators in transplant recipients can lead to acute allograft rejection 1
• The safety and efficacy profiles of these agents in immunosuppressed populations remain largely unknown, as most intervention trials have excluded transplant recipients 1, 5

Long-term Follow-up and Surveillance

• Post-transplantation cancer screening should be tailored to the individual patient 1
• Screening for kidney cancer, post-transplant lymphoproliferative disease, and lung and skin cancer should be implemented in transplant centers worldwide 1
• Current clinical practice relies heavily on evidence from observational studies and registry analyses, highlighting the need for improved data collection and quality 1

Research Priorities

• Development of a global registry for donor surveillance and vigilance 1
• Creation of prediction and simulation models to assess:
  • Risk of transmission from specific donors
  • Risk of death/survival after cancer transmission
  • Risk of death on dialysis versus risk of death after malignancy in kidney transplant recipients 1
• Further research into the mechanisms of cancer pathogenesis, utility of cancer screening, and effects of different immunosuppression regimens 1