SCC-AFTER - Adjuvant Radiotherapy in Patients with High-risk Primary Cutaneous Squamous Cell Carcinoma AFTER surgery (SCC-AFTER): An Open Label, Multicentre, Two-arm Phase III Randomised trial
Recipient organisationNIHR Nottingham Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Jul 2028
In plain English
AI plain-English summary
A third of people with aggressive skin cancers that have been surgically removed will see the cancer return in the same spot or nearby lymph nodes, often with devastating consequences. This trial tests whether giving radiotherapy immediately after surgery—rather than waiting to see if the cancer comes back—can prevent those recurrences. The problem is clear: once a high-risk cutaneous squamous cell carcinoma reappears, it becomes difficult to treat and causes severe pain, disfigurement, and loss of function. Radiotherapy is already used in some NHS hospitals for this purpose, but without solid evidence that it works or is worth its side effects. The trial directly compares outcomes for patients who receive adjuvant radiotherapy versus those who do not, settling a long-standing clinical uncertainty. If the research shows radiotherapy reduces recurrence, it would become standard practice across the NHS, sparing thousands of patients from debilitating local relapses and the treatments that follow. If it does not, the NHS can stop using an ineffective, potentially harmful treatment. Either way, the result will change clinical guidelines and directly affect how skin cancer is managed after surgery.
View original technical description
Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Although cSCC is usually cured by cutting it out surgically, it can reappear in the skin where it started and in the nearby lymph nodes. This is called loco-regional recurrence and it happens in about 1 in 3 people with high-risk cSCCs which are those where the cancer cells look very active under the microscope. Loco-regional recurrence can lead to serious problems such as pain, bleeding, ulceration, infections, disfigurement, loss of physical function, odour, emotional and social distress, and eventually leads to 75% of the deaths caused by cSCC.Loco-regional recurrence after surgery is often due to skin cancer cells having been unknowingly left behind or having broken away into the surrounding skin. One way to reduce the risk of this happening may be to use extra treatment such as radiotherapy in the area where the cancer was removed so that any remaining cancer cells are destroyed. However, we are not sure if using radiotherapy after surgery definitely reduces the risk of high-risk SCC reappearing. Finding out whether radiotherapy helps or not is important:1. To prevent loco-regional recurrence, as once the cancer reappears it is difficult to treat.2. Because radiotherapy is already used in some hospitals to try to reduce the chances of the cancer from returning from where it was removed. Although radiotherapy could be effective, if it is not effective or if it has too many side effects, then we should stop using it across the NHS. However, if effective it should be recommended more widely across the NHS in this way.We asked patients and carers and healthcare teams who look after people with cSCC and they all agree that locoregional recurrence is an important problem and that finding out whether radiotherapy helps or not is an important question.
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