{"registry": "ISRCTN", "registryId": "ISRCTN54806122", "source": "https://www.isrctn.com/ISRCTN54806122", "apiSource": "https://www.isrctn.com/api/trial/ISRCTN54806122/format/default", "fetchedAt": "2026-10-07T17:01:29.051027Z", "license": "CC BY 4.0", "licenseSource": "https://www.isrctn.com/page/faqs#licence-to-post", "study": {"title": "The SCC-AFTER research study aims to find out whether it is better to use radiotherapy or not to prevent high-risk skin cancer from coming back after it has been removed by surgery", "scientificTitle": "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", "acronym": "SCC-AFTER", "hypothesis": "Following complete excision of high-risk primary cutaneous squamous cell carcinoma (HR cSCC) is adjuvant radiotherapy (ART) plus standard clinical follow up superior in reducing loco-regional recurrence compared with standard clinical follow up alone?", "primaryOutcome": "Loco-regional recurrence (LRR)-free survival time, time to LRR is defined as the time from randomisation to date of clinical detection of what is subsequently confirmed to be local, regional, or loco-regional recurrent disease, measured using physical examination at a skin clinic at 4, 8, 16, 12, 24, and 36 months following randomisation until the end of the study", "secondaryOutcome": "1. Quality of life (QOL) measured using EORTC QLQ C30, skin-specific Skin Cancer Index, Picker Patient Experience 15 questionnaire and EQ-5D at 4, 12, 24, and 36 months post-randomisation\n2. Distant metastasis-free survival, defined as days from randomisation to the date of distant metastasis or death from any cause, measured using data reported by completion of recurrence CRF from randomisation until the point of recurrence is confirmed or death\n3. Overall survival, defined as days from randomisation to death for any reason, measured using data reported by completion of a death CRF at the date of death\n4. Safety/toxicity as assessed by common terminology criteria for adverse events (CTCAE) V5.0 scoring system and serious adverse events, including patient-reported outcomes version of the CTCAE, measured using adverse event CRFs at 4, 8, 16, 24, 26 months post-randomisation\n5. Cost-effectiveness measured using health utility using EQ-5D-5L and recording health resource use at 4, 12, 24, and 36 months post-randomisation. The primary economic outcome is cost per quality-adjusted life year (QALY). The secondary economic outcome is resource use and costs.", "intervention": "\n\tThis study aims to find out whether using radiotherapy in people who have had high-risk skin cancer removed by surgery reduces the chances of their skin cancer coming back, or whether radiotherapy is not necessary and only close clinical follow-up is required. This is an open-label, multicentre, two-arm, phase III randomised control trial to evaluate superiority, cost-effectiveness, and effects on quality of life (QoL) of adjuvant radiotherapy (ART) in completely resected high-risk (BWH T2b/3) primary cutaneous squamous cell carcinoma (cSCC). \n\nPatients will be randomised to either the ART followed by close clinical follow-up (ART arm) or close clinical follow-up only (comparator arm and current standard care). Patients will be assessed following UK guidance at baseline, mid-ART (ART arm only), 4 monthly for 2 years, then 6-monthly for year 3. During the follow-up period, QoL and Health Economics (HE) will be assessed twice for year 1, and annually in years 2 and 3. Progression and survival data will be collected throughout the trial.\n\nParticipants will be randomised using unweighted minimisation with a 20% random element. The stratification/balancing variables are detailed below. \nSTRATIFICATION/BALANCING VARIABLES\nThe balancing factors will be:\n•\tAge\no\tLess than 65\no\t>=65 to <80\no\t80 or over\n•\tStage of cancer BWH classification\no\tT2b\no\tT3\n•\tImmunocompromised\no\tYes\no\tNo\n•\tTime since surgery (months)\no\t< Three months\no\tThree to ≤ four months\n•\tPerineural invasion (nerve diameter >=0.1mm)\no\tYes\no\tNo\nEach factor will have equal weighting.\n\nAn internal pilot targeting the recruitment of 100 patients within the first 12 months will determine feasibility. 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-ups. Otherwise, the trial will be analysed when at least 194 events have been reported. \n\nA Quintet Recruitment Intervention (QRI) and INCLUSION Study Within a Project (SWAP) are integrated within the trial to optimise recruitment and inclusion of people with multiple long-term conditions, safeguard informed consent, address clinician equipoise, and identify organisational barriers.\n\tProcedure/Surgery\n\t\n\t\n      ", "condition": "\n\tAdjuvant radiotherapy in patients with high-risk primary cutaneous Squamous Cell Carcinoma (a non-melanoma skin cancer) after surgery\n\tCancer\n\t\n      ", "studyDesign": "Multicentre interventional open-label two-arm Phase III randomized controlled trial", "overallEndDate": "2031-01-01T00:00:00.000Z", "clinicalTrialsGovNumber": "", "lastUpdated": "2026-08-26T08:08:13.208658143Z", "eligibility": {"inclusion": "Current inclusion criteria as of 20/08/2026:\n1. High-risk primary cSCC (T2b/T3 by BWH staging criteria) excised with histologically clear peripheral and deep margins (≥1 mm by RCPath criteria). Surgical excision margins should be consistent with BAD guidelines (peripheral and deep) and will be recorded. \nIf, after surgical excision with curative intent (either wide local excisions with predetermined margins or Mohs micrographic surgery) the deep histological margin is <1 mm, the patient is eligible if ALL of the following are met:\n1.1. For scalp cases only:  the galea aponeurotica (or galeal aponeurosis) must be resected with no evidence of tumour infiltration. If infiltration of the galea is present, the deep histological excision margin must be ≥1 mm).\n1.2. All cases: the MDT is in agreement that surgical treatment is complete;\n1.3. All cases: the pathological size of the deep margin is recorded\n2. Time since excision surgery <3 months (<4 months acceptable only if necessary)\n3. ECOG performance status of 0, 1, 2, or 3 at enrolment (Appendix 1)\n4. Aged 18 years or older at time of consent\n5. Fit for ART and able to attend radiotherapy outpatient appointments\n6. Life expectancy >6 months\n7. Informed Consent obtained* which must be prior to any mandatory study-specific procedures, sampling, and analyses\n\n* Patients should be provided with additional support and adjustments where needed (e.g., layering of information, involvement of a family member/friend as a support person, provide witnessed informed consent if unable to confirm informed consent in writing).\n\nNote: this will include those patients who are elderly, frail and have multiple long-term chronic conditions who are a group at particular risk for cSCC. It will also include immunocompromised patients who are excluded from most clinical trials but have high rates of cSCC.\n\nPrevious inclusion criteria as of 18/02/2026:\n1. High-risk primary cSCC (T2b/T3 by BWH staging criteria) excised with histologically clear peripheral and deep margins (≥1 mm by RCPath criteria*). Surgical excision margins should be consistent with BAD guidelines (peripheral and deep) and will be recorded.\n2. Time since excision surgery < 3 months (< 4 months acceptable only if necessary)\n3. ECOG performance status of 0, 1, 2, or 3 at enrolment (Appendix 1)\n4. Aged 18 years or older at time of consent\n5. Fit for ART and able to attend radiotherapy outpatient appointments\n6. Life expectancy >6 months\n7. Informed Consent obtained** which must be prior to any mandatory study-specific procedures, sampling, and analyses\n\n*For SCC on the scalp, a deep histological margin of 0.8 mm - <1 mm is  eligible if the deep margin of excision was confirmed to have resected either galea or galea and periosteum or galea, periosteum and bone; the galea is not infiltrated by tumour; the peripheral histological margins are 1mm or greater; the SSMDT assesses that surgical treatment is complete\n\nPrevious inclusion criteria:\n1. High-risk primary cSCC (T2b/T3 by BWH staging criteria) excised with adequate peripheral and deep surgical margins (according to BAD guidelines) with histologically clear margins (≥1 mm by Royal College of Pathology criteria\n2. Time since excision surgery < 3 months (<2 months is preferred)\n3. ECOG performance status of 3 or less at enrolment\n4. Aged 18 years or older at time of consent\n5. Fit for ART and able to attend radiotherapy outpatient appointments\n6. Life expectancy >6 months\n7. Informed Consent obtained* which must be prior to any mandatory study-specific procedures, sampling, and analyses", "exclusion": "Current exclusion criteria as of 20/08/2026:\n1. Any current clinicopathological evidence of loco-regional recurrence of the index tumour\n2. Previous (within 2 years) or current non-index primary cSCC in skin drained by the same lymph node basin**\n3. cSCC on anatomical sites which interfere with suitability for ART (such as vermilion lip, eyelids, breast, anogenital area)\n4. Patients with evidence of regional or distant disease at time of primary cSCC diagnosis\n5. Previous radiotherapy to the same area\n6. Patients with reproductive potential who are not willing to use contraception for the duration from trial consent until the last dose of radiotherapy if they are randomised to the ART arm.\n7. Unable to lie still unattended for the duration of ART (estimated to be around 5 minutes)\n8. Participation in another interventional clinical study that may affect the recurrence of cSCC\n9. History of another malignancy where metastasis could cause diagnostic uncertainty or patients receiving active systemic anti-cancer treatment (excluding hormonal treatment for prostate or breast cancer) or radiotherapy***\n\n**Please consider discussing all patients with multiple cSCC draining to the same nodal basin as the index cSCC with the SCC-After trial team including those within the last 3 years.  \n***Please discuss patients with malignancy of concern with the SCC-After trial team  \n\nPrevious exclusion criteria:\n1. Any current clinicopathological evidence of loco-regional recurrence of the index tumour\n2. Previous (within 3 years) or current non-index primary cSCC in skin drained by the same lymph node basin\n3. cSCC on anatomical sites which interfere with suitability for ART (such as vermilion lip, eyelids, breast, anogenital area)\n4. Patients with evidence of regional or distant disease at time of primary cSCC diagnosis\n5. Previous radiotherapy in the same area\n6. Patients with reproductive potential who are not willing to use contraception for the duration from trial consent until the last dose of radiotherapy if they are randomised to the ART arm\n7. Unable to lie still unattended for the duration of ART (estimated to be around 5 minutes)\n8. Participation in another interventional clinical study that may affect the recurrence of cSCC (primary endpoint)\n9. History of another malignancy where metastasis could cause diagnostic uncertainty or patients receiving active systemic anti-cancer treatment (excluding hormonal treatment for prostate or breast cancer) or radiotherapy", "ageRange": "Mixed", "gender": "All", "participantType": "Patient"}, "recruitment": {"recruitmentStart": "2024-07-31T00:00:00.000Z", "recruitmentEnd": "2027-06-14T00:00:00.000Z", "recruitmentStatusOverride": "", "recruitmentStartStatusOverride": "", "targetEnrolment": "840", "totalFinalEnrolment": "0"}, "countries": ["United Kingdom", "England", "Northern Ireland", "Scotland", "Wales"], "locations": [{"name": "The Christie", "city": "Manchester", "state": "", "country": "England", "zip": "M20 4BX"}, {"name": "Kings Mill Hospital", "city": "Sutton-in-Ashfield", "state": "", "country": "England", "zip": "NG17 4JL"}, {"name": "Velindre Cancer Centre", "city": "Cardiff", "state": "", "country": "Wales", "zip": "CF14 2TL"}, {"name": "Nottingham University Hospitals NHS Trust - City Campus", "city": "Nottingham", "state": "", "country": "England", "zip": "NG5 1PB"}, {"name": "Sheffield Teaching Hospitals NHS Foundation Trust", "city": "Sheffield", "state": "", "country": "England", "zip": "S5 7AU"}, {"name": "Tayside", "city": "Dundee", "state": "", "country": "Scotland", "zip": "DD1 9SY"}, {"name": "Cambridge University Hospitals NHS Foundation Trust", "city": "Cambridge", "state": "", "country": "England", "zip": "CB2 0QQ"}, {"name": "Clatterbridge Cancer Centre", "city": "Wirral", "state": "", "country": "England", "zip": "CH63 4JY"}, {"name": "James Cook University Hospital", "city": "Middlesbrough", "state": "", "country": "England", "zip": "TS4 3BW"}, {"name": "Barking, Havering and Redbridge University Hospitals NHS Trust", "city": "Romford", "state": "", "country": "England", "zip": "RM7 0AG"}, {"name": "East Lancashire Hospitals NHS Trust", "city": "Blackburn", "state": "", "country": "England", "zip": "BB2 3HH"}, {"name": "Maidstone & Tunbridge Wells NHS Trust Hq", "city": "Maidstone", "state": "", "country": "England", "zip": "ME16 9QQ"}, {"name": "Churchill Hospital", "city": "Oxford", "state": "", "country": "England", "zip": "OX3 7LE"}, {"name": "Barts and the London NHS Trust", "city": "London", "state": "", "country": "England", "zip": "E1 1BB"}, {"name": "Singleton Hospital", "city": "Swansea", "state": "", "country": "Wales", "zip": "SA2 8QA"}, {"name": "Mount Vernon Cancer Centre", "city": "Northwood", "state": "", "country": "England", "zip": "HA6 2RN"}, {"name": "Norfolk and Norwich University Hospitals NHS Foundation Trust", "city": "Norwich", "state": "", "country": "England", "zip": "NR4 7UY"}, {"name": "Northampton General Hospital", "city": "Northampton", "state": "", "country": "England", "zip": "NN1 5BD"}, {"name": "Queen Elizabeth Hospital", "city": "Birmingham", "state": "", "country": "England", "zip": "B15 2TH"}, {"name": "Royal Surrey NHS Foundation Trust", "city": "Guildford", "state": "", "country": "England", "zip": "GU2 7XX"}, {"name": "Derriford Hospital", "city": "Plymouth", "state": "", "country": "England", "zip": "PL6 8DH"}, {"name": "University Hospitals Dorset NHS Foundation Trust", "city": "Poole", "state": "", "country": "England", "zip": "BH15 2JB"}, {"name": "Musgrove Park Hospital", "city": "Taunton", "state": "", "country": "England", "zip": "TA1 5DA"}, {"name": "Beatson West of Scotland Cancer Centre", "city": "Glasgow", "state": "", "country": "Scotland", "zip": "G12 0YN"}, {"name": "Glan Clywd Hospital", "city": "Rhyl", "state": "", "country": "Wales", "zip": "LL18 5UJ"}, {"name": "Belfast City -Northern Ireland Cancer Centre", "city": "Belfast", "state": "", "country": "Northern Ireland", "zip": "BT9 7JL"}, {"name": "Royal Sussex County Hospital", "city": "Brighton", "state": "", "country": "England", "zip": "BN2 5BE"}, {"name": "Sussex Partnership NHS Foundation Trust", "city": "Worthing", "state": "", "country": "England", "zip": "BN13 3EP"}, {"name": "Royal Berkshire NHS Foundation Trust", "city": "Reading", "state": "", "country": "England", "zip": "RG1 5AN"}], "sponsors": [{"organisation": "Cardiff University", "sponsorType": "University/education", "rorId": "https://ror.org/03kk7td41"}], "funders": [{"name": "National Institute for Health and Care Research", "fundRef": "http://dx.doi.org/10.13039/501100000272"}]}, "studySha256": "d9c128d2e745b6a50e38f611529b0f9d7e5f1479b62ee9cba36cdd276bcb3b02"}