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.

Research summary

Research question In patients who have a high-risk primary cutaneous squamous cell carcinoma (HR-cSCC) surgically excised with clear margins,is adjuvant radiotherapy plus close clinical follow-up superior in reducing the risk of loco-regional recurrence compared with close clinical follow-up alone,and if so,is it cost-effective? Background cSCC is the second most common skin cancer in the UK,with annual incidence exceeding 52,000,increasing by 6% p.a (1,2). Treatment,usually surgery,is curative in 95% (3,4). However,5% of patients develop loco-regional recurrence (LRR) which causes 75% of cSCCspecific mortality,substantial morbidity and reduced quality of life (QoL) (5,6). Approximately 10% of cSCC are high-risk (T2b or T3,BWH classification: 5000 p.a. in the UK) (2),with LRR rates of 20-30% and 50%,respectively (7-11). LRR treatments have limited efficacy and recently approved anti-PD1 immunotherapy for advanced cSCC has complete response rates of 20% (12,13). Adjuvant radiotherapy (ART) after complete excision of HR-cSCC is used to prevent LRR despite evidence limited to non-randomised studies (14-18). Our feasibility surveys of UK specialist skin cancer multidisciplinary teams (SSMDTs) found widespread but variable use of ART in HR-cSCC and simulated case-based discussions in 25 SSMDTs identified consistent clinical equipoise for its use and support for SCC-After (19,20). Interviews and focus groups with patients and their carers have also confirmed the importance of cSCC recurrence and its prevention. Aims / objectives SCC-AFTER is an open label,multi-centre,two-arm,phase III,pragmatic group sequential RCT to evaluate superiority,cost effectiveness and QoL impact of ART after surgery compared to surgery alone in completely resected high-risk (BWH T2b/3) primary cSCC. Methods • Population: Patients (n=840) with completely excised high-risk primary cSCC (T2b/T3 by BWH staging criteria) recruited from 25 UK specialist skin cancer multidisciplinary teams (SSMDTs). • Intervention: ART followed by close clinical follow up • Comparator: close clinical follow up • Inclusion criteria: Adults aged 18 years or older,ECOG ≤3*,fit to receive RT,life expectancy >6 months,including immunocompromised patients and people with multiple long-term conditions (MLTC) (24) • Exclusion criteria: cSCC on anatomic sites which interfere with suitability for ART; any clinical or histological evidence of loco-regional cSCC. • Primary outcome: LRR-free survival time (time from randomisation to date of clinical detection of what is subsequently confirmed to be local,regional or loco-regional recurrent disease). This reflects the natural progression and morbidity of cSCC and its importance is highlighted in the recent core outcomes set for cSCC (21). • Secondary outcomes: QoL; cost-effectiveness; disease free survival; distant metastasis-free survival; overall survival; safety/toxicity. *ECOG 3 must be not due to skin cancer diagnosis An internal pilot targeting recruitment of 100 patients within the first 12 months will determine feasibility. Recruitment prediction is based on site interest and experience on speed of site opening. Two interim analyses after 77 and 115 events (600-760 randomised) trigger early stopping if the log-rank statistic is larger than +/- 3.36 and +/- 2.68 respectively. Stopping for efficacy means fewer participants and shorter follow-up. Otherwise,the trial will be analysed when at least 194 events have been reported. A QuinteT Recruitment Intervention (QRI) and INCLUSION Study within a Project (SWAP) are included to optimise recruitment and inclusion of people with MLTC and other under-served groups,address clinician equipoise and identify organisational barriers

Principal Investigator

Dr Rebecca Shakir

Contact us

Email: latephaseoncology@ouh.nhs.uk

IRAS number

331136