Incidence of Nonmelanoma Skin Cancer Varies by Treatment Modality in Transplant Recipients

The most common form of cancer in recipients of solid organ transplants is nonmelanoma skin cancer (NMSC), which is reportedly more common in recipients of renal transplants than in patients receiving maintenance dialysis. Patients on maintenance dialysis are also at increased risk of NMSC, including patients with high comorbidity and those on the active transplant waiting list.

There are few data available on whether the increased NMSC risk varies by treatment modality for kidney failure. Donal J. Sexton, MD, PhD, and colleagues conducted a retrospective data analysis to determine whether the incidence of NMSC is attenuated during periods of graft loss of function and return to dialysis versus during periods of functioning grafts in recipients of multiple kidney transplants. Results of the analysis were reported online in JAMA Dermatology [doi:10.1001/jamadermatol.2018.4660].

The analysis utilized data from 1994 to 2014 from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry. The analysis was conducted from January 10, 2018, to March 31, 2018. Using Irish census data as the denominator, standardized incidence ratios were calculated for incidence of NMSC in comparison with the general population in Ireland. Poisson regression was used to calculate incidence rates of NMSC and rate ratios. Incidence of NMSC was calculated with modality of treatment for end-stage renal disease varying over time. Disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis.

The primary outcomes of interest were incidence rates per 1000 patient years and incident rates of NMSC following kidney transplant.

The analysis included 3821 individual recipients of living or deceased donor kidney transplant. All participants had a functioning transplanted kidney on January 1, 1994, or received a transplant after that date up to December 31, 2014. Of the total cohort, 37.2% (n=1422) were female, 3215 recipients had one transplant, 522 had a second transplant, and 84 had three kidney transplants. The total exposure time of observation was 35,297 years. Post-transplant, there were 1401 reported cases of NMSC (808 squamous cell carcinoma, 569 basal cell carcinoma, and 24 other/unspecified NMSC), for an incidence rate of 39.69 per 1000 patient-years overall.

The incidence of NMSC diagnosis was higher during periods of treatment with a functioning transplant compared with intervening periods of dialysis (adjusted incidence rate ratio [aIRR], 2.19; 95% confidence interval [CI], 1.56-3.07; P<.001). The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant.

Other risk factors for NMSC in the fully adjusted model were male sex (aIRR, 2.34; 95% CI, 2.05-2.67; P<.001), number of transplants (aIRR, 1.17; 95% CI, 1.04-1.32; P=.01), and patient age (graduated aIRR with increasing age; data not reported).

There was an association between use of tacrolimus and lower incidence of NMSC (aIRR, 0.38; 95% CI, 0.34-0.43; P<.001) compared with use of cyclosporin. The median duration of the dialysis period between the first and second transplants was 2.2 years; between the second and third transplants, the median duration of dialysis was 2.77 years. Median exposure time (exposure to a functioning transplant and the accompanying immunosuppression) for the period of the first transplant was 7.49 years; for the second transplant, 7.47 years; and for the third transplant, 7.37 years.

In analysis with a mixed effects model, there was an independent association between time with a functioning transplant as a covariate and development of NMSC in the fully adjusted model (coefficient, 0.77; 95% CI, 0.68-0.86; P<.001).

The researchers cited some limitations to the analysis, including the retrospective design that made it difficult to capture the effect of the lag between exposure, development of cancer, presentation, and diagnosis, which may vary by treatment period. Further, because kidney transplant clinics tend to have a greater focus on surveillance for skin cancer, the incidence calculations may have been affected by an element of ascertainment bias. However, the researchers noted, patients on maintenance dialysis are also followed closely, so that it is reasonable to expect that clinically significant lesions would be detected in that population as well.

“While the risk of NMSC varies between intervals of graft function and failure, the risk remains high during periods of failure. In addition, in the present study, the elevated incidence of invasive cancer overall in comparison with that of the general population persisted throughout the initial kidney transplant intervals and did not display the sawtooth pattern observed with NMSC incidence. These observations serve to highlight the importance of continued cancer surveillance during periods of graft failure in kidney transplant recipients,” the authors said.

Takeaway Points

  1. Researchers in Ireland conducted a retrospective analysis to determine whether the risk for nonmelanoma skin cancer (NMSC) varies as the end-stage renal disease treatment varies between dialysis and transplant.
  2. A total of 3821 transplant recipients who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2104, were included in the analysis.
  3. There was an association between periods of treatment with a functioning allograft and a higher incidence of NMSC diagnosis compared with periods of graft failure (adjusted incidence rate ratio, 2.19; 95% confidence interval, 1.56-3.07; P<.001).