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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.
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Immunosuppression plays a central role in pathogenesis in addition to other transplant-related and traditional risk factors.
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Nonmelanoma skin cancer is the most common malignancy, followed by posttransplant lymphoproliferative disorder and solid organ tumors.
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De novo malignancies in transplant recipients are more
De Novo Malignancies After Transplantation: Risk and Surveillance Strategies
Section snippets
Key points
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
References (121)
- et al.
Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases
Am J Transplant
(2013) - et al.
The clinical course of kidney transplant recipients after 20 years of graft function
Am J Transplant
(2015) - et al.
Long-term probability of and mortality from de novo malignancy after liver transplantation
Gastroenterology
(2009) - et al.
Comparison of the incidence of malignancy in recipients of different types of organ: a UK registry audit
Am J Transplant
(2010) - et al.
Cancer incidence among Canadian kidney transplant recipients
Am J Transplant
(2007) - et al.
Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009
Eur J Cancer
(2013) - et al.
Increased cancer risk after liver transplantation: a population-based study
J Hepatol
(2001) - et al.
Malignancy after liver transplantation: cumulative risk for development
Transplant Proc
(2009) - et al.
2202 kidney transplant recipients with 10 years of graft function: what happens next?
Am J Transplant
(2008) - et al.
De novo cancer-related death in Australian liver and cardiothoracic transplant recipients
Am J Transplant
(2013)
Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study
Am J Transplant
Cancer mortality in kidney transplantation
Am J Transplant
Malignancies after kidney transplantation: Hong Kong renal registry
Am J Transplant
Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study
Am J Transplant
Comparison of the incidence of de novo malignancy in liver or kidney transplant recipients: analysis of 2673 consecutive cases in a single center
Transplant Proc
Malignancy-related mortality following kidney transplantation is common
Kidney Int
Racial/ethnic differences in cancer risk after kidney transplantation
Am J Transplant
De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases
Transplant Proc
Risk factors associated with the development of skin cancer after liver transplantation
Liver Transpl
Subsequent nonmelanoma skin cancer after liver transplantation
Transplant Proc
Kidney transplant recipients with cutaneous squamous cell carcinoma have an increased risk of internal malignancy
J Invest Dermatol
Incidence of de novo nonmelanoma skin tumors after liver transplantation for alcoholic and nonalcoholic liver diseases
Transplant Proc
Cutaneous malignant melanoma in the Swedish organ transplantation cohort: a study of clinicopathological characteristics and mortality
J Am Acad Dermatol
The impact of preexisting or acquired Kaposi sarcoma herpesvirus infection in kidney transplant recipients on morbidity and survival
Am J Transplant
Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas
Am J Transplant
Who is at risk for post-transplant lymphoproliferative disorders (PTLD) after liver transplantation?
J Hepatol
Epstein-Barr virus infection and posttransplant lymphoproliferative disorder
Am J Transplant
Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation
Blood
De novo internal neoplasms after liver transplantation: increased risk and aggressive behavior in recent years?
Am J Transplant
Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients
Am J Transplant
Monitoring infection with Epstein-Barr virus among seromismatch adult renal transplant recipients
Am J Transplant
Noncutaneous head and neck cancer in solid organ transplant patients: single center experience
Oral Oncol
Extensive surveillance promotes early diagnosis and improved survival of de novo malignancies in liver transplant recipients
Am J Transplant
HPV-related cancers after solid organ transplantation in the United States
Am J Transplant
Characteristics of thoracic malignancies that occur after solid-organ transplantation
J Thorac Oncol
Native renal cysts and dialysis duration are risk factors for renal cell carcinoma in renal transplant recipients
Am J Transplant
The effect of sirolimus on prostate-specific antigen (PSA) levels in male renal transplant recipients without prostate cancer
Am J Transplant
Risk of hepatobiliary cancer after solid organ transplant in the United States
Clin Gastroenterol Hepatol
Spectrum of cancer risk among US solid organ transplant recipients
JAMA
Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection
Liver Transpl
Cancer risk following organ transplantation: a nationwide cohort study in Sweden
Br J Cancer
Liver transplantation and subsequent risk of cancer: findings from a Canadian cohort study
Liver Transpl
Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008–a Swedish population-based study
Int J Cancer
Risk of malignant neoplasms after liver transplantation: a population-based study
Liver Transpl
Long-term cancer risk of immunosuppressive regimens after kidney transplantation
J Am Soc Nephrol
De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population
Transplantation
De Novo neoplasia after liver transplantation: an analysis of risk factors and influence on survival
Liver Transpl
Cancer incidence before and after kidney transplantation
JAMA
Risk of cancer in liver transplant recipients: a look into the mirror
Liver Transpl
Cancer in the transplant recipient
Cold Spring Harb Perspect Med
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Disclosure: All authors report no conflict of interest.