Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression

Abstract

ImportanceCutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients.ObjectiveTo study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant–associated immunosuppressive treatment.Design, Setting, and ParticipantsThis population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022.ExposuresReceipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment.Main Outcomes and MeasuresAbsolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis.ResultsThe study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis.Conclusions and RelevanceIn this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study

“…Consistent with previous studies, 17–19 BWH stage and tumor location on the head and neck were predictive of poor CSCC outcomes in the multivariate analysis. While multiple previous studies have demonstrated an increased risk of poor outcomes in transplant and other immunosuppressed patients, 13,14,20–22 these analyses did not control for tumor stage. Recently, a multi-institutional retrospective cohort study demonstrated that immunosuppressed patients were not at an increased risk of poor CSCC outcomes after controlling for primary tumor stage.…”

Prognostic Outcomes of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Retrospective Comparative Cohort Study

“…This risk was significantly higher in immunosuppressed patients, especially in SOTRs, where up to 4% developed metastasis. Although most cSCC metastases occur within the first 2 years [16], SOTRs appear to have a latency period that can be longer, warranting extended follow-up in high-risk cSCC patients [23,24]. In a recent meta-analysis, the pooled risk of metastasis was significantly higher in SOTRs (7-11%) compared to immunocompetent patients (3.1-8.5%).…”

Effect of education on sun‐safe behaviour in kidney transplant recipients

“…However, in transplant patients, the presence of a skin tumour before transplantation was shown to be associated with a higher risk of subsequent skin tumour development, metastases, graft rejection and death. [16][17][18] To reduce the risk of developing skin tumours, it is essential to raise awareness of the increased risk of skin tumours among patients receiving long-term immunosuppression, as well as to educate them on proper sun protection and sunbathing habits. For preventive purposes, in 2016, we educated a group of kidney transplant patients at the Transplantation Unit of the Department of Surgery of the University of Debrecen about the increased risk of skin tumours, self-examination, adequate sun protection and sunbathing habits through a PowerPoint presentation that we gave in person.…”