Ongoing equipoise contributes to unchanged outcomes and significant morbidity following post-transplant cutaneous squamous cell carcinoma: A Multicentre Cohort Study

IntroductionCutaneous squamous cell carcinoma (CSCC) is the most common post-transplant malignancy, ultimately affecting up to half of all recipients. Historical cohort studies indicate that up to 25% of recipients develop further post-transplant CSCC within 12 months of their first. Post-transplant CSCC incurs doubled risk of metastasis and death compared to the general population and there is uncertainty regarding optimal secondary prevention strategies. Despite evolution of transplant cohort demographics and immunosuppressive regimens, there are no recent studies investigating outcomes after post-transplant CSCC. MethodsA multi-centre retrospective cohort study was undertaken to evaluate current management practices and outcomes following first CSCC in kidney transplant recipients (KTR). Endpoints included development of further CSCC and adverse events including graft loss, solid-organ malignancy, metastatic CSCC, or death with a functioning graft. Multivariate survival modelling identified factors associated with immunosuppression reduction and increased risk of further CSCC and other adverse outcomes. Results136 KTR from eight UK centres with first-ever CSCC diagnosed between 2016 and 2020 were identified. Median (IQR) follow-up was 39 (26-52) months, during which 48.5% developed further CSCC; these data were comparable to those from an international validation cohort. During follow up, 23.3% died, with malignancy being the most common cause of death. Post-CSCC management varied widely within and between centres, with 28.7% of KTR undergoing immunosuppression reduction. ConclusionOur findings demonstrate that outcomes after a first CSCC remain unchanged compared with historical studies, highlighting the urgent need for prospective interventional trials to establish the optimal secondary prevention strategies in this high-risk population. Lay SummaryCutaneous squamous cell carcinoma (CSCC), a type of skin cancer, is the most common cancer in organ transplant patients. Some patients develop more cancers or spread to other organs, but little is known about how best to manage transplant patients after CSCC to prevent further problems. To explore this, we studied a modern-day group of kidney transplant patients from eight UK hospitals after their first CSCC, reviewing how they were treated and what happened afterwards. We found that up to half developed another CSCC within three years. There was no consistent treatment between hospitals, showing that there is uncertainty about the best way to care for these patients. Many patients died or had other serious health problems. These results are similar to older studies from the past 20 years, suggesting little improvement in outcomes. We conclude that transplant patients with their first CSCC remain at high risk of further cancers and other complications. More research is urgently needed to reduce these risks and improve care. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/25328493v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1e335d7org.highwire.dtl.DTLVardef@1e3d80corg.highwire.dtl.DTLVardef@17d1256org.highwire.dtl.DTLVardef@3f0b70_HPS_FORMAT_FIGEXP M_FIG C_FIG