Cancer screening in solid organ transplant recipients: participation, barriers and facilitators, and strategies to improve routine screening.

Cancer in solid organ transplant recipients: Over the last few decades, there has been significant short and medium-term improvement in post-transplant graft and patient survival, owing to improved overall patient care. However, in the long term, transplant recipients suffer substantial complications, such as infections, cardiovascular disease (CVD) and cancer. Among these long-term complications, cancer incidence has risen due to enhanced cumulative immunosuppression exposure [1] and broadening transplant eligibility criteria for elderly recipients [2]. These factors increase the overall cancer risk by approximately 2-4 times in transplant recipients compared to the age and gender-matched general population. The cumulative survival after cancer diagnosis at 5- and 10-years post-transplant is only 50% and 20%, respectively [3]. Cancer is also the leading cause of death among solid organ transplant recipients. The cancer occurrence is due to the interplay of several potential mechanisms, such as altered DNA repair, chronic inflammation, impaired innate and adaptive immune function, and loss of immune surveillance secondary to chronic immunosuppression exposure. This leads to an enhanced predisposition for viral infection-mediated and immune-related cancers. The risk for these cancers is time, sex, and site dependent. For example, the cumulative risk for cancer occurrence after 15 years of transplant rises to 10 to 15%. Similarly, at least one skin cancer risk is around 60% in Europe, Australia, and New Zealand [4]. Likewise, the incidence of non-skin cancers is two-fold higher in women than men [5]. The cancer risk also varies with the type of organ affected, such as cervical cancer risk is about 5-10 times, and the risk of developing colorectal and lung cancer is at least two times higher in the SOTRs compared to the general population. However, the risk for breast and prostatic cancers is similar in both populations [6]. Cancer risk is also age-dependent, as older transplant recipients are more likely to get cancer [7, 8]. Compared to the general population, cancers tend to be more aggressive in the transplant population [9], owing to challenging cancer management in the transplant setting due to coexisting comorbidities and the higher treatment-associated risk of rejection and graft loss. Also, a lack of participation in cancer screening has led to the detection of more advanced-stage cancers, which are unamiable to effective management [1]. As a result, overall, the standardised mortality ratio for cancer is 2.7 for transplant recipients [8]. Cancer screening in the solid organ transplant recipients: Cancer screening is defined as earlier detection of cancer in an asymptomatic individual. It has strongly been advocated in the general population as trial-based evidence showed at least a 20% mortality benefit from breast, colorectal and cervical cancer screening. This mortality benefit is due to the availability of potentially curative anti-cancerous therapies for early-stage cancers. Also, the modelled economic evaluation and trial-based evidence reported that breast, colorectal, and cervical cancer screening are cost-effective in the general population [10]. This can be seen from published data, as the incremental cost-effective ratios (ICER) per life year saved for colorectal cancer screening was under 47000 AUD, irrespective of the type of cancer screening modality, among the Australian population [11]. Similarly, the ICER of $28,921 has been reported in the Canadian population with biennially mammographic screening in women aged 50-69 [12]. Also, human papillomavirus DNA testing on the cervical sample has shown to be cost-effective in developing countries, with a reduction in the lifetime risk of cervical cancer by around 25 to 36 per cent and a cost of less than $500 per life-year saved [13]. This has led to the routine adoption of cancer screening in the general population. While there is no trial-based evidence to support routine cancer screening in solid organ transplant recipients, data extrapolated from the general population and observational studies have suggested routine screening may be beneficial and cost-effective. Despite guideline recommendations, uptake for cancer screening remains poor [10, 14, 15]. For example, as seen from the Canadian data, the screening prevalence of colorectal, cervical and breast cancers was 61.6%, 63.4% and 59.9% in the general populations compared to only 22.5%, 30.2% and 8.6%, respectively, in the SOTRs. There may be many reasons that could impact cancer screening participation among SOTRs, which include ongoing health issues, like cardiovascular diseases and infections [16], fears of death after a cancer diagnosis [17], fears of invasiveness of screening tests and radiation exposure, lack of need for screening due to consideration of being healthy, lack of motivation, primary focus on general and graft health maintenance [10, 17], and less awareness about higher cancer risk with a transplant and screening modalities [18]. Additionally, screening is not entirely benign; it can be invasive and detect low-grade cancer that may not cause any symptoms or problems in the future. Overdiagnosis is defined as screen-detected cancer or pre-cancerous condition that would not have progressed clinically during the person's lifetime and would not be harmful if left undetected. It leads to psychological distress and unnecessary investigations like biopsies [10]. Also, transplant recipients experience competing health risks such as chronic comorbidities, high competing death rates, health priorities, the burden of ongoing long-term treatment and certain complications like infections, impacting further their quality of life and survival [19]. Understanding patients' preferences and perspectives on cancer screening is crucial for a shared decision-making process and provides the basis for an individualized approach to cancer screening; both may facilitate cancer screening participation. While discussing cancer screening strategies and options, the importance of providing balanced information about the benefits and potential harms of screening, risks of cancer-related death, and treatment burden have also been stressed to ensure recipient’s ownership of their clinical care and may facilitate improving their cancer screening compliance [19]. Why is it important to do this review: Current observational data highlights potential barriers and facilitators for the low screening uptake in solid organ transplant recipients. Still, a comprehensive review of the reasons, factors, potential interventions, and strategies to improve cancer screening uptake is lacking. In this scoping review, we aim to identify and summarize all the available evidence to gather information about barriers and facilitators for cancer screening participation, performance characteristics of a cancer screening tool, and potential interventional strategies needed to improve cancer screening participation in SOTRs. Knowledge and understanding of the available evidence on the key aspects of cancer screening participation and factors affecting it will enable identifying the core components necessary to propel meaningful changes at the individual, provider, and organizational levels. References: 1. Chapman JR, Webster AC, Wong GJCSHpim. Cancer in the transplant recipient. 2013;3(7):a015677. 2. Gallagher MP, Kelly PJ, Jardine M, Perkovic V, Cass A, Craig JC, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. 2010;21(5):852-8. 3. Viecelli AK, Lim WH, Macaskill P, Chapman JR, Craig JC, Clayton P, et al. Cancer-specific and all-cause mortality in kidney transplant recipients with and without previous cancer. 2015;99(12):2586-92. 4. Al-Adra D, Al-Qaoud T, Fowler K, Wong GJCJotASoN. De novo malignancies after kidney transplantation. 2022;17(3):434-43. 5. Buxeda A, Redondo-Pachon D, Perez-Saez MJ, Bartolome A, Mir M, Pascual-Dapena A, et al. Gender differences in cancer risk after kidney transplantation. Oncotarget. 2019;10(33):3114-28. 6. Au E, Wong G, Chapman JR. Cancer in kidney transplant recipients. Nat Rev Nephrol. 2018;14(8):508-20. 7. Geissler EKJNRCO. Post-transplantation malignancies: here today, gone tomorrow? 2015;12(12):705-17. 8. Au EH, Chapman JR, Craig JC, Lim WH, Teixeira-Pinto A, Ullah S, et al. Overall and site-specific cancer mortality in patients on dialysis and after kidney transplant. 2019;30(3):471-80. 9. Miao Y, Everly JJ, Gross TG, Tevar AD, First MR, Alloway RR, et al. De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population. 2009;87(9):1347-59. 10. Wong G, Howard K, Tong A, Craig JC, editors. Cancer screening in people who have chronic disease: the example of kidney disease. Seminars in Dialysis; 2011: Wiley Online Library. 11. O'LEARY BA, Olynyk JK, Neville AM, Platell CF. Cost‐effectiveness of colorectal cancer screening: comparison of community‐based flexible sigmoidoscopy with fecal occult blood testing and colonoscopy. Journal of gastroenterology and hepatology. 2004;19(1):38-47. 12. Pataky R, Phillips N, Peacock S, Coldman AJ. Cost-effectiveness of population-based mammography screening strategies by age range and frequency. Journal of cancer policy. 2014;2(4):97-102. 13. Goldie SJ, Gaffikin L, Goldhaber-Fiebert JD, Gordillo-Tobar A, Levin C, Mahé C, et al. Cost-effectiveness of cervical-cancer screening in five developing countries. New England Journal of Medicine. 2005;353(20):2158-68. 14. Kerkhoff BA, O'Connor T, Plant WD, Higgins JR. Poor uptake of reproductive health screening services by female renal transplant recipients. Irish medical journal. 2006;99(3):78-80. 15. Low ESL, Gow PJ, Testro A, Sinclair M. Low participation in preventative health measures in a cohort of liver transplant recipients: A cross-sectional analysis. Clin Transplant. 2021;35(5):e14257. 1

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