A new UK clinical trial, known as SPOT-IT, is investigating whether existing treatments for pre-cancerous skin lesions could help prevent squamous cell carcinoma in people at particularly high risk due to being immunocompromised, as this horizon horizon-scanning feature explains.
Squamous cell carcinoma (SCC) accounts for most non-melanoma skin cancer-related disease. It is the second most common cutaneous malignancy after basal cell carcinoma, and its incidence is increasing worldwide.
While SCC in immunocompetent individuals is usually slow growing and rarely metastatic, people who are immunocompromised are more likely to develop multiple lesions and experience regional or distant spread.
Most cases can be treated surgically, yet repeated operations can have a particularly negative impact, with Professor Catherine Harwood, clinical professor of dermato-oncology at Queen Mary University of London, noting that the surgeries ‘can affect appearance, function and confidence, particularly when cancers occur on visible areas like the face and hands. Over time, this takes a real toll on people’s quality of life’.
This is what the Cutaneous Squamous Cell Prevention using Topical Therapy in Immunosuppressed Patients (SPOT-IT) trial aims to address.
The SPOT-IT trial: rationale and design
Funded by the charity Cancer Research UK and sponsored by Cardiff University, the SPOT-IT trial is led by Professor Harwood alongside Professor Rubeta Matin, associate professor of dermatology at the University of Oxford.
The team is specifically investigating whether earlier intervention against pre-cancerous actinic keratoses could reduce progression to invasive SCC in immunocompromised patients, who often develop recurrent lesions over time.
Such an approach could potentially reduce the need for repeated surgery and lessen cumulative skin damage and metastatic complications.
Current prevention advice for high-risk patients remains largely centred on rigorous sun protection, including regular sunscreen use, protective clothing and avoidance of excessive ultraviolet exposure. Organ transplant recipients are advised to use a broad-spectrum SPF 50 sunscreen that protects against both UVA and UVB rays year-round.
Due to concerns about treatment response and safety, immunocompromised people have often been under-represented in clinical trials, according to Professor Matin, resulting in prevention strategies that are frequently based on evidence from immunocompetent people.
The SPOT-IT trial will recruit immunocompromised participants who have had at least one SCC in the past five years. Participants will be randomised to one of three arms: standard of care daily sunscreen alone, topical 5-fluorouracil (5-FU) plus sunscreen, or 5-FU combined with calcipotriol plus sunscreen.
It follows an earlier feasibility study, published in 2022, which confirmed the rationale for further studies on topical 5-FU-based chemoprevention of SCC in organ transplant recipients.
The 5-FU group will receive treatment over three months, whereas the combination group will receive treatment over 20 days. The schedules will be repeated each year for three years, and the time to develop a new cutaneous SCC will be recorded during the treatment period and for up to four years of follow-up.
Side effects, including pain and redness, as well as quality of life and treatment acceptability, will be evaluated.
Implications for future SCC prevention
Cancer Research UK estimates that there are around 156,000 new non-melanoma skin cancer cases in the UK every year, with incidence rates increasing by 169% since the early 1990s and by 42% in the last decade.
And while non-melanoma skin cancer mortality rates are projected to decrease by 8% between 2023-25 and 2038-40, incidence rates are projected to rise by 14% in the UK during the same period.
This highlights an important unmet need in dermatological oncology: preventing repeated tumour development in patients who remain biologically vulnerable despite routine preventive advice.
SPOT-IT reflects a broader shift in oncology towards proactive cancer prevention in defined high-risk populations rather than relying solely on surveillance and early treatment. This may become increasingly relevant as the incidence of skin cancer continues to rise nationally.
‘What’s unusual about this study is that the outcomes won’t only benefit future patients, but potentially also the participants who are taking part in this trial later in their lives,’ Professor Harwood explains. ‘Because patients tend to develop more of these skin cancers over time, identifying the right prevention strategy really matters over the course of a lifetime.’
For now, standard preventive advice remains unchanged, but, if successful, SPOT-IT may help determine whether targeted treatment of pre-cancerous lesions can offer an additional preventive strategy for patients at greatest risk of aggressive SCC, paving the way for reducing the long-term burden of this disease.