{"entity":{"id":"sins-trial","kind":"trial","name":"SINS (surgical excision against imiquimod cream for basal cell carcinoma)","aka":["SINS","Surgery versus Imiquimod for Nodular and Superficial basal cell carcinoma","ISRCTN48755084"],"tldr":"The largest trial of a cream against an operation for the commonest cancer found the cream is worse, and stayed worse at five years. About one person in six treated with the cream still needed something else done, against one in fifty after surgery. It is still a reasonable choice for some people, but it is not equivalent.","summary":"SINS randomised 501 people at twelve United Kingdom centres between 2003 and 2007 to imiquimod 5 per cent cream or to surgical excision with a 4 mm margin, for primary nodular or superficial basal cell carcinoma at low-risk sites. It was designed as a non-inferiority trial with a pre-specified margin of a relative risk of 0.87, and it was pragmatic: the question was whether a cream a person applies at home can replace an operation.\n\nAt three years, 178 of 213 participants in the imiquimod group (84 per cent) were treated successfully against 185 of 188 (98 per cent) after surgery, a relative risk of 0.84 with a 98 per cent confidence interval of 0.78 to 0.91 and p<0.0001. That confidence interval lies below the non-inferiority margin, so imiquimod was shown to be inferior rather than merely not shown to be non-inferior. At five years the figures were 170 of 206 (82.5 per cent) against 173 of 177 (97.7 per cent), a relative risk of 0.84 (0.77 to 0.91, p<0.001).\n\nTwo findings soften the verdict. Patient-assessed cosmetic outcome did not clearly differ between the groups, and most imiquimod failures happened in the first year, so a lesion that has responded early is likely to stay away. The commonest adverse events were itching (211 against 129 participants) and weeping (160 against 81), and twelve people (5 per cent) withdrew from imiquimod because of side effects against four (2 per cent) from surgery.","status":"negative","asOf":"2026-09-25","links":[{"label":"ISRCTN48755084","url":"https://www.isrctn.com/ISRCTN48755084"},{"label":"ClinicalTrials.gov NCT00066872","url":"https://clinicaltrials.gov/study/NCT00066872"},{"label":"Three-year results (Lancet Oncology 2014)","url":"https://doi.org/10.1016/S1470-2045(13)70530-8"},{"label":"Five-year results (Journal of Investigative Dermatology 2017)","url":"https://doi.org/10.1016/j.jid.2016.10.019"},{"label":"Three-year results on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24332516/"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","skin-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["imiquimod"],"companies":[],"institutions":["nottingham-cancer-centre"],"pathways":[],"terms":["topical-and-destructive-treatment-bcc","surgical-margins-keratinocyte-cancer"],"trials":["mal-pdt-imiquimod-fluorouracil-superficial-bcc","scin-trial","mohs-versus-excision-facial-bcc"],"people":["hywel-williams"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"ISRCTN48755084","phase":"3","setting":"Primary nodular or superficial basal cell carcinoma at low-risk sites, excluding morphoeic and recurrent tumours and people with Gorlin syndrome: imiquimod 5 per cent cream once daily for six weeks (superficial) or twelve weeks (nodular) against surgical excision with a 4 mm margin, with clinical success at three years as the primary outcome and a non-inferiority margin of a relative risk of 0.87","sponsor":"University of Nottingham, funded by Cancer Research UK","result":"Clinical success at three years 84 per cent with imiquimod against 98 per cent with surgery (relative risk 0.84, 98 per cent confidence interval 0.78 to 0.91, p<0.0001), and at five years 82.5 against 97.7 per cent; imiquimod was inferior, not non-inferior.","yearReported":2017,"enrolled":501,"enrolledBasis":"randomised","enrolledNote":"501 participants were randomised at 12 United Kingdom centres between June 2003 and February 2007, 254 to imiquimod and 247 to surgery; the trial is registered as ISRCTN48755084 and also as NCT00066872, and neither record carries a final enrolment figure.","outcomes":[{"endpoint":"Clinical success at 3 years","primary":true,"unit":"%","arms":[{"name":"Imiquimod 5 per cent cream","n":213,"value":83.6,"note":"178 of 213 participants"},{"name":"Surgical excision, 4 mm margin","n":188,"value":98.4,"note":"185 of 188 participants"}],"p":"<0.0001","source":"https://doi.org/10.1016/s1470-2045(13)70530-8"},{"endpoint":"Clinical success at 5 years","unit":"%","arms":[{"name":"Imiquimod 5 per cent cream","n":206,"value":82.5,"note":"170 of 206 participants"},{"name":"Surgical excision, 4 mm margin","n":177,"value":97.7,"note":"173 of 177 participants"}],"p":"<0.001","source":"https://doi.org/10.1016/j.jid.2016.10.019"},{"endpoint":"Withdrawal because of adverse events","unit":"%","arms":[{"name":"Imiquimod 5 per cent cream","n":249,"value":5,"note":"12 participants"},{"name":"Surgical excision, 4 mm margin","n":229,"value":2,"note":"4 participants"}],"source":"https://doi.org/10.1016/s1470-2045(13)70530-8"}],"replication":"The Dutch three-arm trial reached the same place from the other side: imiquimod was the best of the non-surgical options for superficial basal cell carcinoma, and still left about one person in five with a tumour at five years."},"route":"/trials/sins-trial/","neighbours":{"cancer":[{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"imiquimod","kind":"drug","name":"Imiquimod","route":"/drugs/imiquimod/"}],"institution":[{"id":"nottingham-cancer-centre","kind":"institution","name":"Nottingham University Hospitals Cancer Centre (City Hospital)","route":"/institutions/nottingham-cancer-centre/"}],"term":[{"id":"topical-and-destructive-treatment-bcc","kind":"term","name":"Creams, light and cold for basal cell carcinoma","route":"/terms/topical-and-destructive-treatment-bcc/"},{"id":"surgical-margins-keratinocyte-cancer","kind":"term","name":"The margin in skin cancer surgery","route":"/terms/surgical-margins-keratinocyte-cancer/"}],"trial":[{"id":"mohs-versus-excision-facial-bcc","kind":"trial","name":"Mohs surgery against ordinary excision for facial basal cell carcinoma (Nijmegen trial)","route":"/trials/mohs-versus-excision-facial-bcc/"},{"id":"mal-pdt-imiquimod-fluorouracil-superficial-bcc","kind":"trial","name":"Photodynamic therapy against imiquimod against fluorouracil for superficial basal cell carcinoma","route":"/trials/mal-pdt-imiquimod-fluorouracil-superficial-bcc/"},{"id":"scin-trial","kind":"trial","name":"SCIN (curettage then imiquimod against excision for nodular basal cell carcinoma)","route":"/trials/scin-trial/"}],"person":[{"id":"hywel-williams","kind":"person","name":"Hywel Williams","route":"/people/hywel-williams/"}]}}