De Novo Malignancies After Transplantation: Risk and Surveillance Strategies

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Key points

  • De novo malignancies are one of the most common late complications in transplant recipients with functioning graft with 2 to 4 times higher incidence than that in the general population.

  • Immunosuppression plays a central role in pathogenesis in addition to other transplant-related and traditional risk factors.

  • Nonmelanoma skin cancer is the most common malignancy, followed by posttransplant lymphoproliferative disorder and solid organ tumors.

  • De novo malignancies in transplant recipients are more

Incidence and mortality

When compared with the general population, the overall incidence of de novo malignancies is 2- to 4-fold greater in all solid organ transplantation (SOT) recipients.4, 5, 6, 7, 8, 9 Standardized incidence ratio (SIR) for any cancer ranges between 2.4 and 6.5 for RTRs and 1.9 and 3.4 for LTRs (Table 1).4, 5, 6, 7, 8, 10, 11, 12 The reported 5-, 10-, and 15-year cumulative incidence of any de novo malignancy in LTRs is 6.0% to 11.9%, 20.0% to 21.7%, and 55.0%3, 13 and for nonskin cancers 6.7% to

Risk factors for all malignancies

The pivotal role of immunosuppression for development of de novo malignancies has been demonstrated in a study comparing cancer incidence in the same cohort before and after kidney transplantation.24 Immunosuppression may facilitate carcinogenesis by lowering immunosurveillance mechanisms and directly damaging host DNA.25 Another mechanism is the potentiation of the effect of pro-oncogenic viruses, such as human herpes virus type 8 (HHV-8) for Kaposi sarcoma, Epstein-Barr virus (EBV) for PTLD,

Skin Cancer

Nonmelanoma skin cancer (NMSC) is the most common and usually the first detected de novo malignancy in both LTRs and RTRs.4, 11, 32 NMSC is more common in RTRs (SIR 16.6–57.7 for kidney and 6.6–38.5 for liver recipients),4 which may relate to the higher immunosuppression needs of RTRs compared with LTRs. In addition, an observed baseline higher risk has been noted patients with kidney failure when compared with patients with other chronic diseases awaiting SOT.32 Squamous cell carcinoma (SCC)

Surveillance strategies

Based on the guidelines from the AST and ERBPAB,54, 95 the AASLD’s practice guideline,56 the present data, and the recommendations from the general population guidelines, Table 3 summarizes the recommendations for cancer screening.

Two European, retrospective, single-center studies including LTRs have assessed the efficacy of more intensive screening protocols.85, 120 More cancers were detected at earlier stages, and the cancer detection rate increased significantly from 4.9% to 13.0%.85 Both

Summary

Significant progress in surgical techniques, better management strategies, and advances in immunosuppression led to improved overall survival of both LTRs and RTRs. Despite these advances, de novo malignancies remain one of the leading causes of late mortality. Immunosuppression plays a central role for cancer development, although many other transplant-related and traditional risk factors are also involved. More study is needed for optimal immunosuppression regimens that can reduce the risk of

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    Disclosure: All authors report no conflict of interest.

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