Assessment of kidney transplant suitability for patients with prior cancers: is it time for a rethink?

Abstract

Kidney transplant recipients have up to a 100-fold greater risk of incident cancer compared with the age/sex-matched general population, attributed largely to chronic immunosuppression. In patients with a prior history of treated cancers, the type, stage and the potential for cancer recurrence post-transplant of prior cancers are important factors when determining transplant suitability. Consequently, one of the predicaments facing transplant clinicians is to determine whether patients with prior cancers are eligible for transplantation, balancing between the accelerated risk of death on dialysis, the projected survival benefit and quality of life gains with transplantation, and the premature mortality associated with the potential risk of cancer recurrence post-transplant. The guidelines informing transplant eligibility or screening and preventive strategies against cancer recurrence for patients with prior cancers are inconsistent, underpinned by uncertain evidence on the estimates of the incidence of cancer recurrence and the lack of stage-specific outcomes data, particularly among those with multiple myeloma or immune-driven malignancies such as melanomas. With the advent of newer anti-cancer treatment options, it is unclear whether the current guidelines for those with prior cancers remain appropriate. This review will summarize the uncertainties of evidence informing the current recommendations regarding transplant eligibility of patients with prior cancers.

Post renal-transplant malignancy surveillance

“…Large population cohort studies consistently demonstrate a two to four-fold increased risk of cancer in kidney transplant recipients ABSTRACT compared with the age and gender matched general population, particularly for virus related cancers. 6,8,9 The increased risk of malignancy is type specific, with the greatest risk being for Kaposi's sarcoma (80-500 times more frequent), non-melanocytic and melanocytic skin cancers, non-Hodgkin lymphoma, colorectal cancer, renal cell cancer and cancers of the anogenital tract. 9 There is a moderately increased risk of lung cancer and multiple myeloma, but no increase in breast, ovarian, prostate and brain cancers (Table 1 ).…”

“…5,9 The prognosis of kidney transplant recipients who develop recurrent or de novo cancer is relatively poor compared with the general population. 8 Treatment is challenging in this cohort, as optimal management with intensive chemotherapy and surgery may be limited by comorbidities such as cardiovascular disease, and a hesitancy to reduce immunosuppression given the risk of graft rejection and loss. 1,11…”

“…6,14 Immunosuppression is considered the most important risk factor for post-transplant cancer development via multiple mechanisms, including decreased immune surveillance of cancers, decreased antiviral response facilitating unchecked replication of oncogenic viruses, interference with normal deoxyribonucleic acid repair mechanisms, and possibly direct carcinogenic effect of immunosuppressive agents such as ciclosporin and azathioprine. 5,6,8,11 Viral infections (reactivation of latent infection or primary infection) are implicated in several cancers in both the general population and the immunosuppressed. Viruses associated with carcinogenesis in the post-transplant setting include Epstein-Barr virus (EBV), human herpes virus 8 (HHV-8), human papillomavirus (HPV), Merkel cell polyomavirus, hepatitis B and hepatitis C (Table 2 ).…”

“…[4][5][6][7] The increased risk of malignancy is largely attributable to the effect of immunosuppression, which impairs T cell function, immunosurveillance and the immunological control of oncogenic viral infections. 6,8,9 Cancer related mortality rates are also higher in solid organ transplant recipients compared with the general population. 10 While there are clear cancer screening programmes for the general population in the UK, it is unclear how to optimally screen transplant recipients in terms of specific cancers and the frequency and modality of screening test.…”

“…1,11 Early diagnosis may improve outcomes in the transplant recipient, but treatment is often challenging. 1,5,8,9…”