The EADV sponsored the SCOPE-ITSCC metastases study for the years 2016 and 2017. This long-term multi-centre prospective observational study started in 2013 and will finish in 2020. The study was initiated by SCOPE (Skin Care in Organ Transplant Patients Europe, http://www.scopenetwork.org/) in close collaboration with her American sister organisation ITSCC (International Transplant Skin Cancer Collaborative, http://www.itscc.org/).
The burden of cutaneous squamous cell carcinoma (cSCC) is very high among organ transplant recipients (OTR). Many of these patients develop multiple cSCC and some of them develop even more than 100 cSCC. cSCC has the potential to metastasise. This risk varies in the literature between 0.1% and 9.9% per patient. Approximately, 90% of the cSCC metastases will appear within 1 to 2 years after the initial diagnosis of the cSCC. In the immunocompetent population, various criteria are determined which carry a higher risk of regionally or systemically metastases. These variables include tumour localization, size, thickness and histological grade and perineural tumour invasion.
Immunosuppression is often mentioned as a risk factor for developing metastases. In one study the metastatic rate of cSCC is estimated at 13% in the presence of immunosuppression. According to the literature cSCC found in OTR often have a higher proportion of histological high-risk features compared to controls. OTR develop 60- to 100-fold more cSCC than immunocompetent patients.
No prospective clinical studies are available to estimate the role of immunosuppression in metastatic behaviour of a cSCC in OTR. Therefore we planned a study to estimate the cumulative incidence of and risk factors for cSCC metastases in these patients.
The first objective of this study is to estimate the cumulative incidence of metastases of cSCC in OTR during a 2-year follow-up period of the index cSCC.
The second objective is to assess possible risk factors for metastases in these patients such as tumour localisation, tumour size, thickness and grade, perineural tumour invasion and patient-related risk factors such as sex and age, skin type, sun exposure, smoking, number of previous cSCC, immunosuppressive regimen.
Since 2013, 26 centres in 16 countries in Europe (Netherlands, Switzerland, France, Belgium, Italy, Spain, Portugal, England, Scotland, Poland, Turkey, Czech Republic, Austria), USA, Canada and Brazil participate in the study. Until September 2017 we included 417 OTR with 450 SCC. The average age of these patients is 67, with a mean age at transplantation of 48. Most tumours (61%) are located in the head and neck area. Mean tumour size is 2.8 cm, with a range of 0.2-8 cm. Eighty-two percent of the tumours are well or moderate differentiated, while poor or undifferentiated grade is present in 13%. No invasion beyond the dermis is seen in 75% of the SCC.
From the 417 patients, 213 already have reached the minimum of two years of follow-up. From 152 patients with 170 SCC, follow-up data were preliminary analysed. So far, seven patients (5%) had developed a metastasis and 18 patients died during follow-up, of which 4 due to metastasis. Organ metastasis was present in 2 patients (1 lung and 1 bone metastasis). Immune regime during follow up stayed the same in 57.2% of the patients Changes were seen in dose reduction (10.1%), switch or stop of immunosuppressive drug (24.6%) or both (8.0%).
Our goal is to include patients until the summer of 2018. Then the inclusion will stop, and subsequent follow-up will last for two more years. At the end of the study in 2020, we hope to have over more than 500 cSCC included, so that we can properly estimate the cumulative incidence of cutaneous SCC metastases in OTR. This cohort provides prospectively collected data about cSCC. This gives us the opportunity to perform a nested case-control study, with metastasised cSCC and matched non-metastasised cSCC to asses risk factors for metastasis.
Authors: Jan Nico Bouwes Bavinck, Roel Genders and Stella de Jong