CHAPTER 74: Malignancies After Transplantation

NOTE

• We detail malignancies in organ transplant recipients as a whole.

• Observations that apply exclusively to kidney recipients are specifically mentioned.

GENERAL OBSERVATIONS

• Increased incidence of cancers (two to four times) and cancer-related deaths among kidney transplant recipients when compared to the general population^1,13

• The risk is especially marked for malignancies associated with oncogenic viruses such as:

  • Epstein-Barr Virus (EBV, causing Post Transplant Lymphoproliferative Disease, PTLD)

  • Human Herpes Virus 8 (HHV-8, associated with Kaposi Sarcoma, KS)

  • Human Papilloma Virus (HPV, causing nonmelanoma skin cancers and anogenital cancers)¹³

• Malignancies are a major cause of death with functioning grafts among kidney transplant recipients beyond 12 months after transplantation¹

• Cancers account for 8–10% of kidney transplant recipient deaths in the United States (2.6 deaths/1000 patients)¹

• Non-melanoma skin cancers (especially squamous cell carcinoma) are the most frequent malignancy in solid organ transplant recipients^1,13

  • This incidence is as high as 30% in Australia (5/1000 patients)¹

• Genitourinary cancers are the second malignancy in terms of frequency after skin cancers among kidney transplant recipients¹

• Kidney transplant recipients show variation among types of cancers:¹

  • Increased incidence:

    • Lung

    • Colon

    • Liver

    • Lymphoma

    • Melanoma

    • Nonmelanoma skin cancers

  • No reported increased incidence:

    • Prostate

    • Ovarian

    • Brain

    • Cervical cancers

  • Possible reduced incidence

    • Breast cancer

• Increased risk among both dialysis patients and kidney transplant recipients:

  • Thyroid Cancer

  • Myeloma

  • Urinary tract cancers

• Increased risk among transplant recipients than wait list candidates2

  • Nonmelanoma skin cancers

  • Melanoma

  • Kaposi sarcoma

  • Non-Hodgkin lymphoma

  • Mouth cancers

  • Skin cancers

• Lower risk in transplant recipients than among wait list candidates:^1,2

  • Ovarian cancer

  • Prostate cancer

• Diagnosis of malignancy after transplantation:¹

  • Age 40 (average)

  • Within 3–5 years after transplantation

    • Lymphomas and Kaposi sarcomas occur earlier

    • Epithelial cancers occur later

• Renal cancers (85% papillary type, 15% clear cell) occur almost always in the native kidney/s (rather in the transplanted kidney)^1,3:

  • Usually small

  • Can be managed with ablation therapy and no reduction in immunosuppression

• The greater incidence of cardiovascular disease, chronic kidney disease, and infections among transplant recipients increases the risk of potential complications, morbidity, and mortality associated with medical and surgical oncologic interventions.⁴

• Immunosuppressive agents may have a direct carcinogenic power that associates them with malignancies rather than an indirect effect via immunosuppression.⁴

RISK FACTORS^1,3,5

• Risk factors predisposing to malignancies:

  • Age

  • Donor type (from highest to lowest risk)

    • expanded criteria deceased > standard deceased > live donors

  • Immunosuppression

    • Also inclusive of use prior to transplantation for nontransplant indications

  • Length of pretransplant dialysis (increased risk with increased dialysis time)

  • Pretransplant cancers

    • 1.92 hazard ratio of developing de novo malignancies (for solid organ transplant recipients in general)^1,5

  • Rejection

  • Sun exposure

    • Sun blockers and nicotinamide reduce risk of nonmelanoma skin cancers

  • Viral infections

    • Epstein-Barr virus (EBV; Hodgkin and non-Hodgkin lymphomas)

    • Human herpesvirus 8 (HHV-8; Kaposi sarcoma)

    • Human papillomavirus (HPV; cervix, vulva, vagina, anus, and some oropharynx cancers)

    • Merkel cell polyomavirus (Merkel ...