Australian organ transplant recipients (OTRs) are at increased risk of developing keratinocyte cancers (KCs) due to iatrogenic immunosuppression, with a high burden of disease.
Strategies for managing KC risk in patients who have undergone organ transplant include a combination of primary prevention and, treatment of established disease. Australian guidelines since 2008 have recommended that this care be provided in transplant-dedicated specialist clinics, where possible.
Specific treatment strategies include:
- systemic acitretin chemoprophylaxis
- reduction in immunosuppression
- treatment with mechanistic target of rapamycin kinase (MTOR) inhibitors.
Overview of evidence (non-systematic literature review)
Primary prevention of keratinocyte cancer
Skin cancer prevention in OTRs should begin before transplantation, with education about how immunosuppressive medication will raise their risk of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). This should emphasise the need constantly to protect themselves from high sun exposure after transplantation and include education about sun avoidance, especially in the middle of the day, sunscreen use and protective clothing.
A study conducted among OTRs in Queensland found that their use of sun protection measures was suboptimal. The findings of international and Australian studies show that ongoing advice and encouragement about sun protection, given in a clinical setting, appear to be especially effective in achieving behaviour change among people undergoing organ transplantation.
Chemopreventive medicines, including acitretin, capecitabine and vitamin B3 (nicotinamide), have been used to reduce KC risk in people undergoing organ transplantation. However, none of these are established as part of routine preventive care for OTRs.
Role of transplant-dedicated dermatology clinic
The importance of integrated specialist care in the management of skin cancer in organ transplant recipients has been widely recognised.
The various models of care described include:
- transplant-dedicated dermatology subspecialty clinics
- multidisciplinary transplant clinics
- existing dermatology clinics where transplant care is integrated
- high-throughput skin cancer surgery and surveillance clinics for high-risk OTRs
- nurse-led surveillance clinics with consultant dermatologist support
The type of clinic adopted is influenced by available resources.
The UK National Institute for Health and Care Excellence (NICE) recommends that all OTRs be followed up in transplant-dedicated specialist dermatology clinics. The transplant-dedicated dermatology clinic typically comprises dermatologists and dermatologic surgeons with consultation from plastic surgeons, head and neck surgeons, medical oncologists and radiation oncologists as needed. Transplant physicians may consult simultaneously in some clinical settings, and close collaboration with transplant physicians is essential in all clinic models, to co-ordinate care and negotiate adjustments to immunosuppression and commencement of systemic chemoprophylaxis, such as with oral acitretin.
Efficient scheduling of transplant-dedicated specialist clinics increases accessibility, accommodating timely excision of multiple lesions and access to emergency visits. Adequate time and staffing can be allocated to provide surgical management on the day of assessment when appropriate, streamlining care for patients who already commit a significant amount of time to medical appointments, and so facilitating adherence and follow-up (see: Importance of adherence to keratinocyte cancer screening, below).
Dermatology assessment prior to transplantation aims both to treat identified disease and to assess risk, guiding physicians in the timing of transplantation and determining when transplantation may be relatively contraindicated.
The regular surveillance and proactive approach adopted by these clinics promote early detection and treatment, with the aim of improving prognosis and minimising cost. A prospective cohort study of high-risk OTRs followed over 22 years determined that surveillance every 4 months was required to ensure <15% of cancers developed before the subsequent review. Recommendations from this study included 3-monthly reviews for patients who had developed two or more skin cancers and more frequent reviews for those with high-risk tumours or new cancers arising before 3 months, in agreement with other studies.  Patients who were cancer-free for 12 months could be reviewed annually.
Dedicated transplant dermatology clinics provide an opportunity for reinforcing tailored education regarding photoprotection and skin-self surveillance. Education early in the post-transplantation period using multiple methods has been shown to improve long-term retention and behavioural change.
Multidisciplinary care by a team of specialists who understand the unique care needs of OTRs allows for shared decision-making and continuity of care. These clinics also facilitate research and provide opportunities for teaching dermatology trainees who may provide care to OTRs in peripheral settings. 
Importance of adherence to keratinocyte cancer screening
Adherence to screening recommendations has an important effect on clinical outcomes among OTRs. A population-based cohort study of 10,183 OTRs in Canada reported that high adherence to annual dermatology assessments was associated with a 34% reduction in KC-related morbidity or death, compared with low adherence.
- Ng JC, Cumming S, Leung V, Chong AH. Accrual of non-melanoma skin cancer in renal-transplant recipients: experience of a Victorian tertiary referral institution. Australas J Dermatol 2014 Feb;55(1):43-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23808627.
- Ulrich C, Jürgensen JS, Degen A, Hackethal M, Ulrich M, Patel MJ, et al. Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study. Br J Dermatol 2009 Nov;161 Suppl 3:78-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19775361.
- Iannacone MR, Pandeya N, Isbel N, Campbell S, Fawcett J, Soyer HP, et al. Sun Protection Behavior in Organ Transplant Recipients in Queensland, Australia. Dermatology 2015;231(4):360-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26418864.
- Hartman RI, Green AC, Gordon LG, Skin Tumours and Allograft Recipients (STAR) Study.. Sun Protection Among Organ Transplant Recipients After Participation in a Skin Cancer Research Study. JAMA Dermatol 2018 Jul 1;154(7):842-844 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29874380.
- Papier K, Gordon LG, Khosrotehrani K, Isbel N, Campbell S, Griffin A, et al. Increase in preventive behaviour by organ transplant recipients after sun protection information in a skin cancer surveillance clinic. Br J Dermatol 2018 Jun 8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29885042.
- Otley CC, Stasko T, Tope WD, Lebwohl M. Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg 2006 Apr;32(4):562-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16681667.
- Endrizzi B, Ahmed RL, Ray T, Dudek A, Lee P. Capecitabine to reduce nonmelanoma skin carcinoma burden in solid organ transplant recipients. Dermatol Surg 2013 Apr;39(4):634-45 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23379978.
- Chen AC, Martin AJ, Dalziell RA, McKenzie CA, Lowe PM, Eris JM, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol 2016 Nov;175(5):1073-1075 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27061568.
- Christenson LJ, Geusau A, Ferrandiz C, Brown CD, Ulrich C, Stockfleth E, et al. Specialty clinics for the dermatologic care of solid-organ transplant recipients. Dermatol Surg 2004 Apr;30(4 Pt 2):598-603 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15061842.
- Otley CC. Organization of a specialty clinic to optimize the care of organ transplant recipients at risk for skin cancer. Dermatol Surg 2000 Jul;26(7):709-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10886290.
- Papier K, Gordon LG, Khosrotehrani K, Isbel N, Campbell S, Griffin A, et al. Management of organ transplant recipients attending a high-throughput skin cancer surgery and surveillance clinic in Queensland. Br J Dermatol 2018 Jul 13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/30005137.
- Maurice PD, Fenton T, Cross N, Thomson IA, Rennie SC, van Rij AM. A dedicated dermatology clinic for renal transplant recipients: first 5 years of a New Zealand experience. N Z Med J 2013 Feb 15;126(1369):27-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23463107.
- Ali FR, Samarasinghe V, Russell SA, Lear JT. Increasing capacity for skin surveillance in a transplant review clinic. Transplantation 2014 Apr 27;97(8):e48-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24732901.
- Reece SM, Harden PN, Smith AG, Ramsay HM. A model for nurse-led skin cancer surveillance following renal transplantation. Nephrol Nurs J 2002 Jun;29(3):257-9, 267 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12164075.
- National Institute for Health and Clinical Excellence. Improving outcomes for people with skin tumours, including melanoma: The Manual. NHS:National Institute for Health and Clinical Excellence 2006 Abstract available at http://guidance.nice.org.uk/csgstim/?c=91528.
- O'Reilly Zwald F, Brown M. Skin cancer in solid organ transplant recipients: advances in therapy and management: part II. Management of skin cancer in solid organ transplant recipients. J Am Acad Dermatol 2011 Aug;65(2):263-279 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21763562.
- Hofbauer GF, Anliker M, Arnold A, Binet I, Hunger R, Kempf W, et al. Swiss clinical practice guidelines for skin cancer in organ transplant recipients. Swiss Med Wkly 2009 Jul 25;139(29-30):407-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19680830.
- Harwood CA, Mesher D, McGregor JM, Mitchell L, Leedham-Green M, Raftery M, et al. A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population. Am J Transplant 2013 Jan;13(1):119-29 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23072567.
- Ismail F, Mitchell L, Casabonne D, Gulati A, Newton R, Proby CM, et al. Specialist dermatology clinics for organ transplant recipients significantly improve compliance with photoprotection and levels of skin cancer awareness. Br J Dermatol 2006 Nov;155(5):916-25 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17034519.
- Patel PH, Bibee K, Lim G, Malik SM, Wu C, Pugliano-Mauro M. Evaluating Retention of Skin Cancer Education in Kidney Transplant Recipients Reveals a Window of Opportunity for Re-education. Transplant Proc 2017 Jul;49(6):1318-1324 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28736001.
- Leung VKY, Dobbinson SJ, Goodman DJ, Kanellis J, Chong AH. Skin cancer history, sun-related attitudes, behaviour and sunburn among renal transplant recipients versus general population. Australas J Dermatol 2018 May;59(2):e106-e113 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28332195.
- Chan AW, Fung K, Austin PC, Kim SJ, Singer LG, Baxter NN, et al. Improved keratinocyte carcinoma outcomes with annual dermatology assessment after solid organ transplantation: Population-based cohort study. Am J Transplant 2018 Jun 13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29900669.