British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020*

Abstract

Plain language summary available online The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous squamous cell carcinoma (cSCC). The document aims to The guideline is presented as a detailed review with highlighted recommendations for practical use in primary, secondary and tertiary care, in the clinic and in the appropriate skin cancer multidisciplinary team (MDT) meetings (see section 3.0). These may be either local skin MDTs (LSMDTs) or specialist skin cancer MDTs (SSMDTs), depending on the clinicopathological features of the SCC. Clinicians treating people with cSCC should be core members of the appropriate MDT or sanctioned by the MDT to treat the tumour.1 There is also an updated patient information leaflet available on the BAD website (https://www.skinhealthinfo.org.uk/a-z-conditions-treatments/). The guideline does not cover This set of guidelines has been developed using the BAD’s recommended methodology;5 further information can be found in Appendix J (see Supporting Information) with reference to the AGREE II instrument (www.agreetrust.org)6 and GRADE (https://www.gradeworkinggroup.org). Recommendations were developed for implementation in the UK National Health Service (NHS). The guideline development group (GDG) consisted of seven consultant dermatologists (representing England, Northern Ireland, Scotland and Wales), two consultant clinical oncologists (radiation oncologists), a consultant plastic surgeon, a consultant maxillofacial surgeon, a dermatopathologist, a general practitioner, a Macmillan dermatology clinical nurse specialist, two patient representatives and a technical team (consisting of an information scientist, a guideline research fellow and a project manager providing methodological and technical support). The GDG established several clinical questions pertinent to the scope of the guideline and a set of outcome measures of importance to patients, ranked according to the GRADE methodology7 (see section 2.1; and Appendix A; see Supporting Information). The GDG agreed to adopt the Royal College of Pathologists dataset for the histological reporting of cSCC.8 Along with Public Health England, this endorses the Union for International Cancer Control 8th edition (UICC8)9 (Tables 1 and 2), rather than the American Joint Committee on Cancer 8th edition cancer staging manual, which covers only head and neck cSCC.10 The GDG agreed that risk is part of a spectrum and not dichotomous, and the evidence from the literature searches supported a division based on low-, high- and very high-risk status. As shown in Figure 1, this division was achieved by integrating clinical, pathological, tumour–nodes–metastasis (TNM) staging and margin criteria. A systematic literature search of the PubMed, MEDLINE, Embase and Cochrane databases was conducted by the technical team to identify key articles on cSCC from 1 January 2007 to 30 January 2020; the search terms and strategies are detailed in Appendix K (see Supporting Information). Additional references relevant to the topic were also isolated from citations in the reviewed literature and the previous versions of the guidelines.11, 12 Data extraction, critical appraisal and data synthesis were performed by the technical team, who prepared the evidence summaries, lists of excluded studies and PRISMA diagram. Evidence from included studies was rated according to the GRADE system (high, moderate, low or very low quality). Recommendations are based on evidence drawn from systematic reviews of the literature pertaining to the clinical questions identified, following discussions with the entire GDG and factoring in all four factors that would affect their strength ratings according to the GRADE approach (i.e. balance between desirable and undesirable effects, quality of evidence, patient values and preferences, and resource allocation). All GDG members contributed towards drafting and/or reviewing the narratives and information in the guideline and supporting information documents. When there was insufficient evidence from the literature, informal consensus was reached based on the experience of the GDG. The summary of findings with forest plots (Appendix B), clinical evidence summary (Appendix C), tables Linking the Evidence To the Recommendations (LETR) (Appendix D), GRADE evidence profiles indicating the quality of evidence (Appendix E), summary of included studies (Appendix F), narrative findings for noncomparative studies (Appendix G), PRISMA flow diagram (Appendix H) and list of excluded studies (Appendix I) are detailed in the Supporting Information. The strength of recommendation is expressed by the wording and symbols shown in Table 3. The GDG established a number of clinical questions pertinent to the scope of the guideline (for a full review protocol see Appendix A in the Supporting Information). The GDG also established a set of outcome measures of importance to patients for each clinical question, which were ranked according to the GRADE methodology7 by the patient representatives. This uses a nine-point scale, with outcomes ranked 9 being those the patient representatives considered most important. Outcomes ranked 9, 8 or 7 are critical for decision-making; those ranked 6, 5 or 4 are important but not critical for decision-making; and those ranked 3, 2 or 1 are the least important for decision-making. Data on these outcome measures were extracted from the included studies (Appendixes B, C, E, F and G; see Supporting Information). Review question 1: treatment In people with ‘higher-risk’ primary cSCC, how clinically effective are surgical (standard and Mohs) and nonsurgical treatments (radiotherapy and electrochemotherapy) compared with each other? Review question 2: treatment In people with low-risk primary cSCC how clinically effective are surgical (standard excision, Mohs, curettage and cautery, cryosurgery and carbon dioxide laser) and nonsurgical treatments (topical therapies, photodynamic therapy or radiotherapy) compared with each other or with no treatment (observation)? (Radiotherapy includes brachytherapy where appropriate.) Review question 3: surgical margin In people with cSCC who undergo standard surgical excision, what surgical margin and surgical plane should be used? Review question 4: involved margins In people with cSCC who undergo excision of the primary tumour and where histological analysis shows either one or more involved or clear-but-close margins (< 1 mm), what is the appropriate subsequent management? Review question 5: adjuvant radiotherapy In people with primary cSCC following surgical excision with clear histological margins, what is the role of adjuvant radiotherapy in reducing the risk of local recurrence? [‘Adjuvant’ in the guidelines refers to any treatment (radiotherapy) after primary treatment (surgery).] Review question 6: metastatic squamous cell carcinoma In people with any metastasis from cSCC how clinically effective are standard surgical and nonsurgical treatments (chemotherapeutic therapy, radiotherapy, immunotherapy) compared with each other or with no treatment (observation)? (Radiotherapy includes brachytherapy where appropriate.) Review question 7: follow-up In people with a diagnosed higher-risk cSCC what is the appropriate follow-up period following treatment? Note: in Mohs surgery the tumour is curetted or surgically debulked, and the defect usually excised with a small (1–2 mm) margin of surrounding skin. The patient waits with a dressed wound pending histological confirmation by the Mohs surgeon that the tumour has been completely removed. If residual tumour is identified, a further layer of tissue is removed, and the process repeated until the surgical wound is confirmed to be tumour free. The wound is then repaired by conventional surgical techniques. There are few randomized controlled trials (RCTs) to support the following guidelines for the management of cSCC. The following recommendations and ratings were agreed upon unanimously by the core members of the GDG and patient representatives. The recommendations cover suspected and diagnosed cSCC. All recommendations would also generally relate to children, young people and adults, unless specified otherwise. Those under 24 years of age with cSCC should be managed by the SSMDT but must additionally be referred to the appropriate children’s, teenagers’ or young adults’ service for their specific expertise. These guidelines do not include specific recommendations for subungual or periungual SCCs. For further information on the wording used for recommendations and strength of recommendation ratings see Table 3. The evidence for recommendations is based on the studies as listed (for details and discussion of the evidence see Appendixes B–F in the Supporting Information). The GDG recommendations relating to referral pathways are based on discussion and clinical experience, as evidence-based details are not available at the time of writing. The GDG is aware of the lack of high-quality evidence for some of these recommendations, and therefore strong recommendations with an asterisk (*) are based on available evidence, as well as consensus and specialist experience. Good practice point (GPP) recommendations are derived from informal consensus. R1 (↑↑) Obtain histological confirmation of cSCC lesions in the event of diagnostic uncertainty, before planning definitive treatment. This must be a representative sample of the tumour; in most instances, this will be a full-thickness incisional biopsy ideally incorporating both the peripheral and the deep margins. R2 (GPP) Offer discussion on the risks and benefits of all treatment options (outcomes, function, cosmesis) to people with cSCC and their families or carers and make the treatment decision together. R3 (↑↑) Record the maximum clinical cSCC lesion dimension prior to any diagnostic or treatment procedure (usually diameter, in millimetres), the plane of the deep-excision margin, whether it is a recurrent tumour or in field of previous radiotherapy, and the immune status of the patient, on the specimen request form for the pathologist. R4 (GPP) Take a good-quality clinical photograph of the cSCC lesion for the patient record to aid future management and assessment of the area after healing. In multisite disease the lesions to be treated should ideally be marked on the photograph to limit the risk of wrong-site procedures. R5 (↑↑) Offer* standard surgical excision as the first-line treatment option to people with resectable primary cSCC. R6 (↑↑) Peripheral tumour margins should be determined under bright lighting and magnification or dermoscopy. Excise* with a clinical peripheral surgical margin of For definition of the levels of risk see Figure 1.13-18 R7 (↑↑) Ensure at least a 1-mm histological clearance of cSCC excisions at all margins by including sufficient peripheral and deep tissues (see R6 for appropriate standard surgical excision margins). R8 (↑↑) Manage and report excised cSCC specimens according to the Royal College of Pathologists dataset.8 R9 (GPP) Document the risk status of cSCC tumour as low risk, high risk or very high risk in the patient notes (Figure 1). R10 (↓↓) T1 cSCC tumours excised with histologically clear margins of at least 1 mm, in the absence of other high-risk factors, do not need routine discussion at an MDT (Figure 1). R11 (↑↑) Review the histology of people with cSCC with one or more involved or clear-but-close margins (< 1 mm) at an appropriate skin MDT (Figure 1). R12 (↑) Consider the risk factors for the patient and the margin, site and tumour stage in people with cSCC with one or more clear-but-close margins (< 1 mm). Consider observation in immunocompetent people with cSCC with a low-risk tumour (Figure 1). R13 (↑↑) Offer further wide local excision (with likely delayed reconstruction), Mohs micrographic surgery, or adjuvant radiotherapy to people with cSCC with one or more involved margins, or close margins (< 1 mm), where patient or tumour factors confer higher risk. R14 (GPP) Offer active treatment to immunosuppressed people with cSCC with one or more clear-but-close (< 1 mm) or involved margins with structured follow-up and surveillance. R15 (↑↑) Discuss at an SSMDT people with cSCC with symptomatic perineural invasion and/or radiological evidence of perineural invasion. If discussed at a skin MDT, skull base or head and neck MDT opinion may be required. Aggressive surgical excision of the involved nerve should be the first step, where technically possible, followed by consideration of adjuvant radiotherapy. R16 (↑) Consider Mohs micrographic surgery in selected people with cSCC following SSMDT discussion, particularly where tumour margins are difficult to delineate or in sites where tissue conservation is important for function. R17 (↑↑) Discuss people with histologically proven cSCC being considered for radiotherapy at an MDT (LSMDT or SSMDT) with a clinical oncologist present. R18 (↑↑) Offer primary radiotherapy R19 (↑) Consider adjuvant radiotherapy in people with cSCC R20 (↑↑) Offer adjuvant radiotherapy to people with incompletely excised cSCC, where further surgery is not possible (or is not chosen by the patient) and in those at high risk of local recurrence R21 (↓↓) Do not offer postoperative radiotherapy to people with completely excised T1 or T2 cSCC and with microscopic, dermal-only, nerve diameter < 0·1 mm perineural invasion. R22 (↑) Consider conformal radiotherapy including the entire course of the involved nerve in people with cSCC with symptomatic perineural invasion and/or radiological evidence of perineural invasion when surgery is inappropriate, after carefully weighing the benefits and side-effects from radiotherapy to such an extensive radiotherapy treatment field. R23 (GPP) Inform younger people with cSCC (age < 60 years), especially if they are an organ transplant recipient, of the very low risk of radiation-induced, in-field malignancy in the future. Take this risk into account when making any treatment decision. R24 (↑) Consider curettage and cautery with curative intent in immunocompetent people with small (< 1 cm), well-defined, nonrecurrent, clinically low-risk cSCC. R25 (GPP) Review the histology of cSCC removed by curettage and cautery to identify high-risk or very high-risk features. If these are identified, the case should be discussed at an appropriate MDT regarding further management. R26 (GPP) Do not routinely offer imaging of the draining nodal basin to people with cSCC in the absence of suspected or clinically detectable nodal high-risk such as or cSCC, a high risk of metastasis and consideration can be to of the in the clinically (↑↑) an and imaging treatment for people (GPP) assessment of the of a primary cSCC including in the (GPP) biopsy for high-risk of primary cSCC in the of a clinical or SSMDT (GPP) Offer to people with cSCC with clinically If they are and this can be core or histology may be required. (GPP) imaging of the involved area in people with cSCC with in metastasis or perineural invasion of Discuss with a if is metastasis is a of metastasis in which skin cancer a and to between the area of previous treatment and the nodal (↑↑) Offer to people with head and neck cSCC with is a surgical procedure in which the that the site of the tumour are removed to an that has rather than diagnostic or The tissue is under the for of is to the of and to identify metastatic disease see The head and neck imaging should include or and imaging of the as a The surgery should be performed by a surgeon who is a core of the SSMDT and with (↑↑) Offer to people with and neck cSCC with in or other peripheral draining is to the of and to identify metastatic disease see In the imaging should include the and as a and the surgery should include levels In the imaging should include the and to and the surgery should include and deep (↑↑) Offer adjuvant radiotherapy following to people with cSCC with high-risk two or more and by as (GPP) Consider surgical (with or adjuvant radiotherapy) or primary radiotherapy in people with recurrent cSCC. (GPP) Consider or basin in selected people with cSCC for disease in the of especially in those treatment. (↑) Consider immune treatment in people with cSCC where curative surgery or radiotherapy is not or those with metastatic cSCC, patients with organ or those who (↑) Consider or in people with metastatic cSCC with to immune are generally and is in and and consideration for should be are for cSCC in the (GPP) Consider in people with cSCC in if other local or are not (↑↑) Offer to a key to people with cSCC, ideally a clinical nurse specialist, as part of an treatment information on the and management of cSCC. (GPP) people with cSCC by the skin and and with any other appropriate clinical (GPP) people with cSCC on and and by providing appropriate and information (GPP) Offer people with low-risk cSCC a where to skin and nodal and patient on and of at the information on the risk of further cSCC and on how to a including the into the system if they a (GPP) Offer people with high-risk cSCC when several risk factors follow-up at for 12 then at for a further 12 The follow-up should be with to skin and patient on may be with other to and skin according to local by the appropriate skin (GPP) Offer people with very high-risk cSCC follow-up at for 24 then at for a further 12 The follow-up should be with to skin and patient on may be with other to and skin according to local by the appropriate skin who a high risk of further primary cSCC, such as organ transplant should under skin surveillance. (GPP) Offer people with metastatic cSCC follow-up at for 24 then at for a further with review on patient should be performed on the of clinical with SSMDT discussion if There is insufficient evidence to support any recommendation for or in the treatment of cSCC. The following list future research recommendations should identify which clinicopathological or factors which a system for risk. need to include more people with cSCC, with of the by risk skin cancer clinical studies need to outcomes by (i.e. or cell and for primary cSCC reporting recurrence quality of and and effects, including and All future cSCC need to report outcome measures time to to and of data A the and resource of treatment options for people with cSCC in the UK strategies for people with cSCC, not to radiotherapy, or metastatic cSCC in immune are There is a need for a review of the treatments of cSCC in those who are at risk of those with or The role of biopsy in the staging of very high-risk cSCC the of these tumours to The recommendations, discussions in the (Appendix see Information) and consensus specialist experience were used to the and of 2 and cutaneous squamous cell carcinoma is a tumour that from the of the or is and has the to The of skin cancer is at least higher than that of the most tumour in the which is evidence that this is an for skin cancer to cSCC is the most cancer in the and to not only in the UK but also in other This will an on planning for and on is usually to and is therefore especially in people with and may also be for the of these may as a of previous to and or such as or or or from lesions such as in 24 A high of cSCC is found in with where it is a of In the of cSCC is not with immune function, for those following organ or for and those with or are at risk of this are with The risk of cSCC with the (for or has to be There is evidence with that from the use of and to support use of and effective in the of and These measures are particularly important for people who therapy for skin may also be at higher cSCC may also in patients who are being treated with for with organ are at high risk of cSCC. to and and measures to cSCC, should be part of their routine In patients with or high-risk consideration should be to and the use of which may also be in other high-risk should also be considered in this such as and and photodynamic may in skin and therefore the risk of skin in high-risk transplant but evidence is usually as an or tumour that may or it may as an evidence of All patients in there is a of a cSCC should be referred to an specialist who is to an usually in their local dermatology skin cancer The of skin cancer specimens and their and reporting should to the Royal College of Pathologists dataset for primary cSCC.8 The Royal College of Pathologists and Public Health for the staging of and skin In the patients with cSCC is there clear for or evidence of the The surgical margins of excision and see Note: these are 4 mm for mm for high-risk and mm for very high-risk cSCC. margins in all following standard surgical Note: these are as clear 1 mm), clear but close (< 1 mm) or involved mm). follow-up and see by members of the MDT, including clinical nurse Note: follow-up are one for and a follow-up 4 in the first then in the and very a follow-up 4 in the first and then in the The recommendation of is to in the to a patient and between (Appendix see Supporting Information). The document and Supporting were available to the BAD the Royal College of the Royal College of Pathologists the Royal College of the of and the of and the of and the for the the of Cancer and the The were considered by the GDG. further the was for review by the of the BAD of the prior to for This document has been prepared on of the BAD and is based on the data available when the document was is that under it may be to from the guidelines and that the of future studies may some of the recommendations to be to to these guidelines should not be considered should to these recommendations a a of the review to and references was a decision but the this may some important information in other The for this set of recommendations is for where important will be updated on the BAD are very to for on the and and for their at the of these the patient representatives and for their in the clinical of the reviewing the evidence and the recommendations, as well as all of those who on the the Data Data Data Data Data Data Data Data J Data Data Data Data A Data Data analysis The following were the of the guideline Cancer and and research and for of the and of the guidelines development group for cSCC of the skin cancer of the skin cancer has in a general of the Cancer of the of the skin cancer clinical for appraisal of for cSCC for of the of the skin cancer Cancer prior to on for Royal College of Pathologists on Cancer and they no of Appendix A Review Appendix Appendix evidence Appendix Linking Evidence To Recommendations Appendix GRADE evidence Appendix F of included Appendix findings for Appendix PRISMA Appendix excluded from Appendix J Appendix K Appendix data and data The is not for the or of any supporting information by the than should be to the for the