Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period

Simple Summary Solid-organ transplant recipients are known to be at higher risk of developing several cancer types, mainly virus-related malignancies. Monitoring trends in the incidence of post-transplant cancers among individuals who received solid organ transplantation helps to improve preventive measures and outcomes. This cohort study aimed to examine, over a 25-year period in Italy, variations in the occurrence of post-transplant cancers among 11,418 recipients of kidney transplantation (KT). Cancer incidence over three periods (1997–2004; 2005–2012; and 2013–2021) was analyzed within the cohort and in comparison with the general population. After multivariate adjustment, both approaches highlighted reduced risks of Kaposi’s sarcoma, whereas no statistically significant changes over time in the incidence of other cancers were noted. Accordingly, the results of this study highlighted the need to sustain and strengthen cancer-preventive actions in KT recipients. Abstract This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997–2004 to 21.0 in 2013–2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76–1.07 in 2005–2012; IRR = 0.72, 95% CI: 0.60–0.87 in 2013–2021 vs. 1997–2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi’s sarcoma (KS; IRR = 0.37, 95% CI: 0.24–0.57 in 2005–2012; IRR = 0.09, 95% CI: 0.04–0.18 in 2013–2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26–2.85 in 1997–2004; SIR = 1.99, 95% CI: 1.83–2.16 in 2013–2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

[1]  Yawen Hou,et al.  Individual dynamic prediction and prognostic analysis for long-term allograft survival after kidney transplantation , 2022, BMC Nephrology.

[2]  K. Lemström,et al.  Cancer risk and mortality after solid organ transplantation: A population‐based 30‐year cohort study in Finland , 2022, International journal of cancer.

[3]  Marco Fiorentino,et al.  The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients , 2021, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  A. Wiseman,et al.  Long-Term Immunosuppression Management: Opportunities and Uncertainties. , 2021, Clinical journal of the American Society of Nephrology : CJASN.

[5]  D. Al-Adra,et al.  De Novo Malignancies after Kidney Transplantation , 2021, Clinical journal of the American Society of Nephrology : CJASN.

[6]  D. O. Dahle,et al.  Renal Cell Carcinoma and Kidney Transplantation: A Narrative Review , 2021, Transplantation.

[7]  H. Welch,et al.  The Rapid Rise in Cutaneous Melanoma Diagnoses. , 2021, The New England journal of medicine.

[8]  Alla Turshudzhyan Post-renal transplant malignancies: Opportunities for prevention and early screening. , 2020, Cancer treatment and research communications.

[9]  K. Budde,et al.  De-novo malignancies after kidney transplantation: A long-term observational study , 2020, PloS one.

[10]  E. Engels,et al.  Changes in cancer incidence and outcomes among kidney transplant recipients in the United States over a thirty-year period. , 2020, Kidney international.

[11]  P. Morris,et al.  Declining incidence of keratinocyte carcinoma in organ transplant recipients , 2019, The British journal of dermatology.

[12]  P. Morris,et al.  Post‐transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group , 2019, Clinical transplantation.

[13]  D. Serraino,et al.  Decreased incidence of Kaposi sarcoma after kidney transplant in Italy and role of mTOR‐inhibitors: 1997–2016 , 2019, International journal of cancer.

[14]  A. Steffan,et al.  Dissecting the Multiplicity of Immune Effects of Immunosuppressive Drugs to Better Predict the Risk of de novo Malignancies in Solid Organ Transplant Patients , 2019, Front. Oncol..

[15]  A. Teixeira-Pinto,et al.  Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney Transplant. , 2019, Journal of the American Society of Nephrology : JASN.

[16]  S. Tang,et al.  An update on cancer after kidney transplantation. , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  R. Pfeiffer,et al.  Risk of Kaposi sarcoma after solid organ transplantation in the United States , 2018, International journal of cancer.

[18]  S. Acuna Etiology of increased cancer incidence after solid organ transplantation. , 2018, Transplantation reviews.

[19]  J. Chapman,et al.  Cancer in kidney transplant recipients , 2018, Nature Reviews Nephrology.

[20]  T. Karlsen,et al.  Decreasing incidence of cancer after liver transplantation—A Nordic population‐based study over 3 decades , 2018, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[21]  S. Kim,et al.  Cancer evaluation in the assessment of solid organ transplant candidates: A systematic review of clinical practice guidelines. , 2018, Transplantation reviews.

[22]  P. Gjersvik,et al.  Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study , 2017, JAMA dermatology.

[23]  E. Engels Cancer in Solid Organ Transplant Recipients: There Is Still Much to Learn and Do , 2017, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  J. Krisl,et al.  Chemotherapy and Transplantation: The Role of Immunosuppression in Malignancy and a Review of Antineoplastic Agents in Solid Organ Transplant Recipients , 2017, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[25]  J. D. de Fijter,et al.  Cancer and mTOR Inhibitors in Transplant Recipients. , 2017, Transplantation.

[26]  L. Moore,et al.  Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[27]  D. Serraino,et al.  Epidemiology of de novo malignancies after solid-organ transplantation: immunosuppression, infection and other risk factors. , 2014, Best practice & research. Clinical obstetrics & gynaecology.

[28]  A. Webster,et al.  Cancer in the transplant recipient. , 2013, Cold Spring Harbor perspectives in medicine.

[29]  G. Edgren,et al.  Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—A Swedish population‐based study , 2013, International journal of cancer.

[30]  D. Serraino,et al.  Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009. , 2013, European journal of cancer.

[31]  A. Israni,et al.  Spectrum of cancer risk among US solid organ transplant recipients. , 2011, JAMA.

[32]  T. Schulz Cancer and viral infections in immunocompromised individuals , 2009, International journal of cancer.

[33]  R. Alloway,et al.  De Novo Cancers Arising in Organ Transplant Recipients are Associated With Adverse Outcomes Compared With the General Population , 2009, Transplantation.

[34]  K. Chou,et al.  De novo malignancies after kidney transplantation. , 2007, Urology.

[35]  L. A. García-Astudillo,et al.  Human herpesvirus-8 infection and Kaposi's sarcoma after liver and kidney transplantation in different geographical areas of Spain. , 2006, Transplant immunology.

[36]  S. Franceschi,et al.  Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients , 2005, British Journal of Cancer.

[37]  K Ulm,et al.  A simple method to calculate the confidence interval of a standardized mortality ratio (SMR) , 1990, American journal of epidemiology.

[38]  M. Gail Statistical methods in cancer research. Volume II. The design and analysis of cohort studies. N. E. Breslow and N. E. Day, Oxford University Press for International Agency for Research on Cancer, 1987. No of pages: xii + 406. Price: £30 , 1989 .

[39]  Norman E. Breslow,et al.  The design and analysis of cohort studies , 1987 .