These patients are 11 times more likely to die from skin cancer than the general population, with keratinocyte cancer driving the excess mortality despite declining death rates over time.
Kidney transplant recipients in Australia and New Zealand remain at markedly increased risk of dying from skin cancer despite three decades of advances in prevention and treatment, according to a large population-based study that highlights the need for ongoing surveillance and rapid treatment pathways.
Researchers linked data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) with national death registries to examine skin cancer mortality among 21,503 people who received their first kidney transplant between 1990 and 2019.
Results have been published in the British Journal of Dermatology.
It is well understood that transplant recipients have an increased incidence of skin cancer and death from skin cancer, but the extent to which demographics and geography impact excess skin cancer mortality among transplant recipients relative to the general population was unknown, the researchers wrote.
Previous studies have shown transplant recipients have up to a 60-fold higher incidence of keratinocyte cancer than the general population, but data on mortality have been limited.
“Cancer is an important cause of death after transplant, accounting for 27% of deaths in recipients with a functioning kidney transplant in Australia and New Zealand,” the researchers wrote.
“Transplant recipients are at increased risk of most cancers, due to long-term immunosuppression to prevent transplant rejection, which increases susceptibility to oncogenic viruses, and alters T-cell immunity, DNA replication and repair.”
The cohort studied by the researchers contributed more than 212,000 person-years of follow-up, providing one of the largest analyses of skin cancer mortality in transplant recipients undertaken in high ultraviolet (UV) exposure settings.
During follow-up, 251 recipients died from skin cancer, including 82 deaths from melanoma and 169 from keratinocyte cancers.
Overall skin cancer mortality was 118.2 deaths per 100,000 person-years, with melanoma accounting for 38.6 deaths per 100,000 person-years and keratinocyte cancers 79.6 deaths per 100,000 person-years.
Compared with the general population, kidney transplant recipients had an 11.1-fold higher risk of dying from skin cancer.
The excess risk varied by tumour type, with recipients 4.5 times more likely to die from melanoma and 34.5 times more likely to die from keratinocyte cancer.
The researchers said the findings reinforced that keratinocyte cancers, which were relatively uncommon causes of death in immunocompetent people, represented a major source of mortality in transplant recipients receiving long-term immunosuppressive therapy.
Although men experienced higher absolute mortality than women, with skin cancer mortality rates of 149.1 versus 70.1 deaths per 100,000 person-years, the relative increase in mortality compared with the general population was greater among women.
Women had a standardised mortality ratio (SMR) of 12.7 compared with 10.7 for men, with the difference driven largely by keratinocyte cancer mortality.
The researchers noted that clinicians should not assume female transplant recipients were at lower risk simply because skin cancer mortality is generally lower among women in the broader population.
“It is important that clinicians recognize that keratinocyte cancer in a transplant recipient does not have the same mortality risk as an age- and sex-matched person from the general population in which death is rarer, particularly in younger people,” they wrote.
“However, it is important to note that all kidney transplant recipients had higher relative mortality compared with the general population, so all transplant recipients should be considered to be at high risk.”
Age-related findings also challenged assumptions about risk. Absolute mortality increased with age, but excess mortality relative to the general population was seen across every age group and was particularly pronounced among younger and middle-aged recipients.
Keratinocyte cancer mortality relative to the general population was highest in recipients aged 30-49 years at death, while melanoma mortality was greatest in those aged 50-59 years.
No skin cancer deaths occurred in recipients younger than 30 years during follow-up, although numbers in this group were small.
Geography also influenced outcomes. Absolute mortality was highest in Queensland, Tasmania, Western Australia, and New Zealand, while excess mortality compared with the general population peaked in Queensland, Western Australia, and New Zealand. Queensland recipients had the highest overall SMR at 14.8, followed by Western Australia at 13.1, and New Zealand at 11.0.
The researchers suggested the findings reflected the influence of high ambient UV radiation, although they noted that skin cancer mortality remained substantially elevated across every Australian jurisdiction and New Zealand.
Importantly, the mortality gap did not close over the three decades studied. Absolute skin cancer mortality declined over time, but mortality also declined in the general population, leaving transplant recipients with persistently elevated relative risks.
The highest excess mortality occurred during 2000-2009 but remained substantially increased in the most recent decade of follow-up.
The researchers suggested improvements in public awareness of sun protection, advances in melanoma treatment and changes in immunosuppressive regimens have benefited transplant recipients to some extent, but not enough to eliminate the disparity with the general population.
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Nearly all skin cancer deaths occurred in White recipients, who accounted for 98% of fatalities, consistent with the well-established burden of skin cancer in fair-skinned populations living in Australia and New Zealand.
The median interval from transplantation to death was seven years for melanoma and 10 years for keratinocyte cancer, highlighting the prolonged period during which recipients remain vulnerable to aggressive skin malignancies.
The researchers said the findings support intensive prevention strategies throughout the transplant journey, including education on sun protection, regular dermatological surveillance and prompt access to specialist skin cancer treatment.
They said clinicians should recognise that keratinocyte cancers in transplant recipients behave far more aggressively than in immunocompetent patients and required early diagnosis and timely management.
The persistence of excess mortality among women, younger recipients and those living in regions with high UV exposure also suggests these groups warrant particular clinical attention rather than being considered relatively low risk, they reiterated.
“Our findings that women, young and middle-aged kidney transplant recipients have excess skin cancer mortality supports close surveillance and prompt treatment after diagnosis remains critical to address excess skin cancer mortality in transplant recipients who might otherwise be considered lower-risk groups in the general population,” they concluded.
“Future work may explore how changing therapeutics for skin cancer treatment since 2019 has affected mortality rates.”
