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. 2021 May 17;2021(5):CD014590. doi: 10.1002/14651858.CD014590

Surgical excision methods for skin cancer involving the nail unit

Claire Hardie 1,✉, Ryckie G Wade 2, Justin CR Wormald 3, Brian Stafford 4, Faye Elliott 2, Julia Newton-Bishop 2, Donald Dewar 1
Editor: Cochrane Skin Group
PMCID: PMC8127530

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To assess the efficacy and safety of different methods of surgical excision for skin cancer involving the nail unit.

Background

Please see Table 1 for a glossary of terms. 

1. Glossary.

Term Definition
Acral lentiginous subtype Subtype of melanoma mainly occurring on the nailbeds, palms and soles (Bradford 2009)
Aetiology Cause or origin of a disease
Amelanotic Clinical appearances of little or no brown pigment on visual inspection (Pizzichetta 2004)
Breslow thickness Depth of melanoma tumour in millimetres (Breslow 1970)
Distal phalangeal joint Joint between distal and middle phalanx
Distal phalanx Bone at the tip of fingers and toes
Erythronychia Red streaks in the nail (de Berker 2004)
Germinal matrix Proximal nailbed that generates the nail plate (de Berker 2013)
Hyponychium Skin beneath the free edge of the nail plate
Leukonychia White discolouration of nails
Middle phalanx Middle bone of the fingers and toes
Neurovasculature Structures that supply sensation and blood flow
Paronychia Inflammation or infection of the skin around the finger or toenail
Periosteum A membrane on the surface of bones
Proximal phalangeal joint Joint between middle and proximal phalanx
Proximal phalanx Bone at the bottom of fingers and toes
Pyogenic granuloma Reactive proliferation of small blood vessels
Sterile matrix Nailbed
Subungual hyperkeratosis Scaling under the nail due to excess keratin production
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Description of the condition

Skin cancer arising on the digits of the hands or feet is rare, and occasionally affects the nail unit. The nail unit comprises the nail plate, which arises from the nail bed and is surrounded on all sides by supporting soft tissues and their neurovasculature. These structures are adherent to the periosteum of the distal phalanx and closely related to the insertion of the terminal extensor tendon (de Berker 2013; Shum 2000).

Squamous cell carcinoma (SCC) is believed to be the most common malignant tumour involving the nail unit, although it is rare and the exact incidence is unclear (Richert 2013). Nail unit SCC has been associated with human papillomavirus rather than ultraviolet (UV) light but the exact aetiology remains uncertain (Ashinoff 1991; Riddel 2011). SCC of the nail unit is typically slow growing and initial symptoms include leukonychia, subungual hyperkeratosis and erythronychia (Dalle 2007). It is poorly recognised and can mimic other conditions such as nail trauma or verruca vulgaris which can also lead to a delay between onset of symptoms and diagnosis (de Berker 1996). SCC is staged according to the eighth edition of the American Joint Committee on Cancer (AJCC) system (Amin 2017). Tumours involving the nail have a higher rate of recurrence than SCCs in other sites (Riddel 2011), however death from metastatic SCC originating on a digit is rare and only a few cases have been reported (Richert 2013).

Cutaneous melanoma involving the nail unit is a rare variant accounting for approximately 1% to 3% cases of melanoma in the white population (Banfield 1998; Blessing 1991). It is part of the acral lentiginous subtype, which typically presents late with a greater Breslow thickness, and is associated with poorer outcomes (Teramoto 2018). Breslow thickness is defined as the depth of the melanoma tumour, in millimetres (mm), from the most superficial part of the granular layer to the deepest tumour cell (Breslow 1970). The aetiology of acral melanoma is also unknown as it is not associated with UV light exposure (Cochran 2014). Given its prevalence on the weight‐bearing areas of the sole of the foot, chronic microtrauma is a suggested causative factor (Al‐Hassani 2017). Melanoma involving the nail unit may present as a brown or black streak under the nail plate extending into the hyponychium (O'Connor 2011; Quinn 1996), although it can also be amelanotic (Koch 2000). There is poor recognition of the condition by physicians and the general public (Levit 2000), which leads to delays in presentation and diagnosis (Dika 2016). Five‐year survival rates with this condition vary from 16% to 80% (Cochran 2014), with more recent studies demonstrating a median overall survival of 40 to 55 months (Ogata 2017; Reilly 2017). Melanoma is also staged according to the AJCC (Amin 2017).

Basal cell carcinoma (BCC) of the nail unit is the most rare, with only case reports available in the literature (Forman 2007). The most significant aetiological factors for BCCs are reported as UV radiation and genetic disposition (Gailani 1996), but additionally trauma has been suggested as an aetiological factor in nail unit BCC (Bandyopadhyay 2011). The most common presenting complaint is ulceration, which is present in over half of cases (Martinelli 2006). Again, it is a poorly recognised condition and diagnosis is frequently delayed (de Giorgi 2005; Kim 2000). It often initially misdiagnosed as benign conditions such as trauma to the nail, chronic paronychia or pyogenic granuloma and may also mimic malignant conditions including SCC and melanoma (Martinelli 2006). Metastasis of any BCC is extremely rare (Ting 2005) and rates of recurrence for BCCs of the nail unit are not reported.

Description of the intervention

The principle treatment for both cutaneous SCC, melanoma and BCC is surgical excision. However, several different methods of surgery are utilised for skin cancer involving the nail unit. The options can be challenging to resolve for patients and surgeons, due to the desire to preserve the length of the digit and the conflicting need for wide excision in the form of an amputation (Zaiac 2001). Overall, these options can be simplified into surgery that preserves the digit or amputation. There are no consensus statements nor guidelines which explicitly deal with the surgical techniques for treating SCC of the digit and consequently, the ideal surgical margin which balances disease‐free survival and morbidity remains unclear. The treatment of cutaneous melanoma is wide excision; however, the required margins remain a matter of active research interest (Moncrieff 2018) and there are also no clear guidelines concerning melanoma of the digit. Similarly for BCC, there are no guidelines specifically for treating this condition in the nail unit.

Digit‐sparing surgery

Wide excision

For malignancies involving the nail unit, surgeons may elect to remove the tumour and subcutaneous tissues but spare the skeleton and major structures of the digit (tendons, nerves, vessels, etc.). The recommended margins for SCC are 4 mm for low‐risk tumours and 6 mm for high‐risk tumours or tumour with histological thickness of more than 6 mm (Motley 2002). For cutaneous melanoma the recommended peripheral excision margin depends on the Breslow thickness of the tumour; in the UK, the following clinical margins for excision are advised (Marsden 2010).

  • In‐situ disease: 5 mm margin.

  • Tumours less than 1 mm: 1 cm margin.

  • Tumours between 1.01 mm and 2 mm: 1 cm to 2 cm margin.

  • Tumours between 2.1 mm and 4 mm: 2 cm to 3 cm margin.

  • Tumours over 4 mm: also 2 cm to 3 cm margin.

However, excision margins remain strongly debated and most of the studies concerning peripheral margins excluded tumours on the extremities (Lens 2007). The recommended margins for BCC are 4 mm for low‐risk tumours and up to 15 mm for high‐risk tumours (Telfer 2008). 

Mohs surgery

Mohs micrographic surgery is a margin‐controlled excision technique which uses intraoperative stepwise histological examination of the margins by the operating surgeon (Mohs 1941). It aims to achieve histological clearance whilst sparing the maximal amount of normal tissue. Typically, the malignancy can be completely excised and reconstructed in one day, although the procedure can be lengthy and there can be difficulty preparing the sections for analysis of melanocytic tumours (Erickson 2010). When digit‐sparing surgery is performed (whether by conventional wide excision or micrographic surgical means) the aim is to enable reconstruction by means of skin graft(s) or flap(s) to retain a useful digit.

Amputation

When preservation of the digit is not desired or possible, amputation may be performed. Indeed, such surgery is recommended by many groups for both primary SCC (Dalle 2007) and melanoma involving the nail unit (de Berker 1996; Dasgupta 1965; Heaton 1994). Shortening digits may confer cosmetic and functional impairment but offers improved chances for complete excision (Cohen 2008). The digit can be amputated at various levels (typically disarticulation at the distal or proximal interphalangeal joints) depending on the desired margin of clearance, expected residual function and the patient’s wishes.

How the intervention might work

Digit‐sparing surgery may be effective in treating malignancies involving the nail unit without the associated morbidity of amputation. There is conflicting evidence regarding the risk of recurrence for both SCC and melanoma when digit‐sparing surgery is used, compared to amputation (Dalle 2007; Neczyporenko 2014). The concern with digit‐sparing surgery over amputation is that the narrower margins used may be associated with increased risk of recurrence (Thomas 2004). Digit‐sparing surgery also significantly reduces the deep margin due to the paucity of soft tissue between the nail unit and distal phalanx (Kim 2011), although it has been reported that the nail matrix is more resistant to tumour invasion than typical dermis so digit‐sparing surgery may still be appropriate (Shin 2014). Although BCC of the nail unit is rare, digit‐sparing surgery seems to be used more frequently (Forman 2007); this is likely because of the slow growing nature of this tumour (Telfer 2008).

Why it is important to do this review

Skin cancer of the nail unit is associated with significant morbidity and melanoma has a high mortality rate. There is a diversity in practice in the management of these cancers involving the nail unit and there are increasing rates of digit‐sparing surgery reported in the literature. However, any difference in outcomes between digit‐sparing surgery and amputation are not clear, nor is it clear how these interventions affect patients' quality of life. These are important considerations for patients and clinicians when deciding on treatment for these conditions, and by undertaking this Cochrane Review we wish to provide a comprehensive summary of the treatment options and associated outcomes.

Objectives

To assess the efficacy and safety of different methods of surgical excision for skin cancer involving the nail unit.

Methods

Criteria for considering studies for this review

Types of studies

We are aware of the limited evidence from randomised controlled trials (RCTs) in this clinical area, hence we are considering more than one study design. All assessment and reporting will be carried out separately for each study design. We will include the following studies, without restriction on language or publication status.

  • Randomised controlled trials, including quasi‐ and cluster‐RCTs. Cross‐over trials will be excluded as this design is inappropriate for the clinical condition under examination.

  • Non‐randomised controlled studies of surgical management of nail unit cancers.

  • Longitudinal observational studies directly comparing digit‐sparing surgery to amputation. These will include observational studies of prospective cohort or those of nested case‐control design with an appropriate comparator group. Case series and case reports will be excluded. 

Types of participants

We will include all participants (all ages and ethnic groups) with histologically proven primary cutaneous SCC, melanoma or BCC of the finger, toe or thumb, which is associated with the nail unit. Tumours of all histological thicknesses (AJCC stage 0, I, II, or IIIa; Amin 2017) will be included, and those without documented histological thickness will be considered. Tumours without a defined histological thickness are common in the nail unit as the initial incision biopsy can disrupt measurement.

Types of interventions

The interventions of interest for nail tumours are wide local excision, Mohs surgery and amputation. Studies comparing any of the three interventions will be considered.

Types of outcome measures

Primary outcomes

  1. Overall survival, defined as from date of diagnosis to date of any cause death at five years (or the closest time point to five years)

  2. Progression free survival, defined as from date of diagnosis to date of any disease progression or any cause death at five years (or the closest time point to five years)

  3. Adverse events/outcomes, to include any wound problem within 30 postoperative days (e.g. infection, wound breakdown, need for reoperation)

Secondary outcomes

  1. Quality of life (e.g. measured using the EuroQol EQ‐5D (Rabin 2001), Medical Outcomes Study Short‐Form Health Survey (SF‐36) (Ware 1992), Sickness Impact Profile (SIP) (Bergner 1981) or Quality of Well‐Being (QWB) scale (Kaplan 1993)). Quality‐of‐life outcomes will be assessed at six months (or the closest time point to six months)

Search methods for identification of studies

We aim to identify all relevant trials, regardless of language or publication status (published, unpublished, in press, or in progress).

Electronic searches

The Cochrane Skin Information Specialist will search the following databases for relevant trials, with no restriction by date. A draft search strategy for MEDLINE (Ovid) has been devised, which is displayed in Appendix 1. This will be used as the basis for search strategies for the other databases listed.

  • The Cochrane Skin Specialised Register.

  • The Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library.

  • MEDLINE via Ovid (from 1946 onwards).

  • Embase via Ovid (from 1974 onwards).

Trial registers

We (CMH, RGW) will search the following trials registers/portals using the terms: nail and (cancer or tumo/ur or neoplasm or melanoma or carcinoma).

  • The World Health Organization International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).

  • ClinicalTrials.gov (www.clinicaltrials.gov).

Searching other resources

References from published studies

The references of relevant systematic reviews and reports of included studies will be searched for further references to relevant studies.

Unpublished literature

We will contact experts in the management of skin cancer to enquire if they are aware of additional relevant trials.

Correspondence with trialists/experts/organisations

We will contact original authors for clarification and further data if trial reports are unclear.

Conference proceedings

We will search Web of Science's Conference Proceedings Citation Index. Conference abstracts from the following meetings will be handsearched if they are not already included in the Cochrane Skin Specialised Register or Embase.

  • Journal of Plastic, Reconstructive and Aesthetic Surgery (European Society of Plastic and Reconstructive Surgery conference).

  • British Association of Plastic and Reconstructive Surgery abstract archives.

  • American Society of Plastic Surgery abstract archives (Plastic Surgery: The Meeting).

  • Canadian Journal of Plastic Surgery (Canadian Society of Plastic Surgery Annual Meeting).

Adverse effects

We will not perform a separate search for adverse effects of different surgical excision methods for skin cancer of the nail unit. We will consider adverse effects described in included studies only.

Data collection and analysis

Selection of studies

The titles and abstracts of deduplicated references will be downloaded to Covidence systematic review software (Covidence), which will be used for the primary screening. All titles and abstracts will be screened by two independent review authors (CMH and RGW). Full texts will be downloaded for all potentially relevant studies and two independent review authors will determine final eligibility (CMH and RW). Any disagreements will be resolved by consensus or with input from a third review author (JCRW). Serial publications from the same dataset will be excluded. The number of included and excluded studies will be presented in a study flow diagram. Reasons for excluding full texts will be provided in the study flow diagram and in the 'Characteristics of excluded studies' tables.

Data extraction and management

Data pertaining to SCC, melanoma and BCC will be collected and analysed separately as they are distinct clinical entities. For included studies the following information will be collected and entered into the 'Characteristics of included studies' table: study design and methods; participant characteristics (age, sex); study setting; tumour characteristics (type of malignancy, site, size depth, invasion, ulceration); participant immunosuppression; intervention (wide local excision, Mohs surgery or amputation, including details of margins obtained/level of amputation); duration and timing of follow‐up; details of the primary outcomes and method of analysis. Details of any variables the authors have adjusted for will also be collected.

These items will be collected on a customised pro forma which will be piloted. Two independent review authors(CMH and RGW) will extract the data which will then be checked by a third author (JCRW) and entered into Cochrane's review‐writing software, RevMan Web (RevMan Web 2020). Authors will not be blinded to the study authors, institution or journal.

Assessment of risk of bias in included studies

We will assess the risk of bias of included studies using the guidance from appropriate sections of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). We will assess risk of bias for the results included in the 'Summary of findings' tables (see section 'Summary of findings and assessment of the certainty of the evidence').

For randomised studies, we will use version 2 of the 'Risk of bias' tool (RoB 2) (Sterne 2019), which provides algorithms and signalling questions to assess risk of bias. The effect of interest is assignment to treatment. The domains in the RoB 2 tool are: bias arising from the randomisation process; bias due to deviations from intended intervention; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported results (Higgins 2019). We will answer a number of signalling questions resulting in the tool algorithm classifying each domain as 'high risk of bias', 'low risk of bias', or 'some concerns'. The tool algorithm will also decide whether the overall risk of bias is 'high risk', 'low risk' or 'some concerns'.  To undertake these assessments we will use the RoB 2 Excel Tool. Consensus decisions for the signalling questions will be made available as supplemental files. We do not anticipate finding any cluster‐RCTs, but if these are included then we will still use RoB 2 but we will add a domain specific to cluster‐RCTs from the archived version of the tool (Domain 1b ‐ 'Bias arising from the timing of identification and recruitment of participants') (Eldridge 2016). We will also make use of the guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).

For non‐randomised studies we will use the ROBINS‐I (Risk Of Bias In Non‐randomised Studies) tool (Sterne 2016). We will examine all the domains of ROBINS‐I, which are: bias due to confounding; bias in participant selection; bias in classification of interventions; bias due to deviation from intended interventions; bias due to missing data; bias in measurement of outcomes and bias in selection of the reported result (Sterne 2016). The study will be classified as: no information on which to make a judgement, or low, moderate, high, or critical risk of bias. If any studies reach critical risk of bias in any domain we will not continue with the assessment as those studies will be excluded from the main effects analysis, according to ROBINS‐I guidance.

Covariates can be an issue in non‐randomised studies and can occur when variables (or factors) may be involved in predicting the initial intervention received (Sterne 2016). In this study we will consider tumour stage/Breslow thickness to be covariates due to possible preferences of treating patients with early disease more conservatively. The healthcare systems participants are treated in will also be considered as covariates due to potential differences in stage of diagnosis and local treatment preferences. These were defined following discussion with experienced clinicians and review of the literature. There are no cointerventions of interest to consider here.

Assessment of risk of bias will be performed by two independent review authors (CMH and RGW). Any disagreements will be resolved by consensus or with input from a third author (JCRW). To summarise the assessment, the risk of bias will be presented in a ‘Risk of bias’ graph and a narrative summary will be provided. Outcomes may be measured at different time points between the studies and this will need to be discussed. Analysis of outcomes at fixed time points should help to address this.

Measures of treatment effect

Depending on the quality and type of data available we will report hazard ratios (HRs) and 95% confidence intervals (CIs), for the outcomes of disease‐specific survival and overall survival. If either adjusted or unadjusted HRs are not available, we will attempt to extract any available data for the estimation of odds ratios (ORs) or risk ratios (RRs) and 95% CIs. For continuous outcomes or outcomes measured in scales (such as pain) we will express the mean difference (MD) and standard deviation. If different scales are reported, then the standardised mean difference (SMD) shall be calculated, where appropriate. For analysis of adverse events we will use RRs and 95% CIs. 

Unit of analysis issues

Following advice from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019), we will consider combining groups for single pair‐wise comparisons, e.g. digit‐sparing surgery compared to amputation. For participants who initially had digit‐sparing surgery then subsequently went on to have amputation for any reason, we will consider the primary surgery as the intervention and the amputation as an adverse outcome. We expect no cluster‐RCTs but if they are included the appropriate adjustments will be made if the required information is available, according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019).

Dealing with missing data

We will contact the authors of papers or abstracts with missing data to request additional information.

Assessment of heterogeneity

There is likely to be heterogeneity between the studies due to the variation between tumours and the use of varying surgical techniques. This will be discussed in the review. We will describe potential sources of clinical heterogeneity and downgrade the certainty of evidence according to GRADE criteria (Guyatt 2011). If pooling of studies is feasible, between‐study heterogeneity will be visually inspected on a forest plot for outlying studies and variability of estimated effects between studies, alongside a Chi2 statistic with CIs. A low P value (i.e. less than 0.10) will be used as significant evidence of heterogeneity (Higgins 2019). We will also assess statistical heterogeneity using the  I2 statistic. We will interpret heterogeneity as potentially unimportant if the I2 statistic is 0% to 40%; likely to be moderate if the value is from 50% to 80%; and substantial if the value is above 80%. If the I2 statistic is high (over 80%) we will explore this further and consider not pooling the data, after checking the direction of the effect (Higgins 2019).

Assessment of reporting biases

If more than 10 studies are included in a meta‐analysis a funnel plot will be used to assess publication bias (Sterne 2011).

Data synthesis

Any data synthesis will be carried out and reported separately for all considered study designs. Data pertaining to SCC, melanoma and BCC will be analysed separately as they are distinct clinical entities. This will be done for each of the four outcomes comparing digit‐sparing surgery (wide local excision or Mohs surgery) to amputation (total 12 comparisons). 

Prior to any pooling of data, the bias of included studies will be assessed and the effects only pooled if participants of included studies are clinically homogeneous. Meta‐analysis will be performed for studies with comparable participants and methodology that are not at critical risk of bias (Sterne 2019), using RevMan Web (RevMan Web 2020). We will only pool similar effect measures where sufficient data are available.

For time‐to‐event outcomes we will use either generic inverse variance modelling using hazard ratios (DerSimonian 1986) or comparison of dichotomous outcomes (Maentel‐Hanzel). We will prefer the adjusted HRs if there is similarity between the studies in their chosen adjusting variables, otherwise the unadjusted HRs will be used.

We expect the outcome data to be presented in various formats, from simple proportions through to time‐to‐event data; we will attempt to recover as much data as possible, as explained above. We expect the quality‐of‐life data to be reported as a scalar value; if the same scales are used then mean differences (MDs) between groups will be presented. If different quality‐of‐life tools are reported, then between‐group differences will be presented using the standardised mean difference (SMD). We anticipate clinical heterogeneity and will use random‐effects models in all analyses. If there is substantial heterogeneity which cannot be explained using subgroup or sensitivity analyses (or both), or the studies are at critical risk of bias, then a meta‐analysis will not be performed and instead the original data will be presented in tables.

Subgroup analysis and investigation of heterogeneity

To explore heterogeneity, we will undertake an analysis stratified by tumour stage, in accordance with AJCC staging (Amin 2017). For melanoma, we will use four categories according to Breslow thickness: less than 1.0 mm; 1 mm to 2 mm; 2 mm to 4 mm; and more than 4 mm. For SCCs and BCCs, we will use four categories according to tumour dimension: 2 cm or less; greater than 2 cm to below 4 cm; 4 cm or greater with minimal erosion of bone; and tumours with extensive bone involvement. Subgroup analysis will also be undertaken for local, regional and distant recurrence. If other unexplained heterogeneity occurs we will consider subgroup analysis by participant age and for those with SCC we will also consider subgroup analysis based on immunosuppression.

Sensitivity analysis

We will perform sensitivity analysis for risk of bias, by temporarily removing from the pooled analysis studies at high risk of bias.

Summary of findings and assessment of the certainty of the evidence

We will present two separate 'Summary of findings' tables for SCC and melanoma, for the comparison of digit‐sparing surgery versus amputation. The content of each will reflect the synthesis of each of our study outcomes: 1) overall survival at five years (or the closest time point to five years); 2) progression‐free survival at five years (or the closest time point to five years); 3) adverse events (wound problems) up to 30 days postoperatively; and 4) quality of life at six months (or the closest time point to six months). BCC will not be included in the 'Summary of findings' tables due to the rarity of the condition. Ideally, RCT data only will be used for each outcome in the tables but non‐randomised data will be presented if limited RCT data are available. 

The GRADE approach will be used to assess the certainty of evidence for each outcome. GRADE includes the assessment of five factors: study limitations (risk of bias), inconsistency of results, indirectness of evidence, imprecision, and publication bias (Schunemann 2013). Each outcome can be downgraded by one or two levels for each domain, and the overall certainty will be classed as either high, moderate, low or very low. Two review authors (CH and RGW) will perform the GRADE assessments independently, and any disagreement will be resolved via discussion or input from a third review author (JCRW). We will use GRADEpro GDT to create the 'Summary of findings' tables (GRADEpro GDT 2015).

Acknowledgements

We thank Cochrane Skin for their advice and support.

The Cochrane Skin editorial base wishes to thank Michael Bigby for acting as Dermatology Editor for this protocol; the Statistical Editor, Ben Carter; the Methods Editor, Ching‐Chi Chi; and the clinical referee, Tracey Vlahovic. We would also like to thank Ann Littlewood, who reviewed the search methods, and Jessica Sharp, who copy‐edited the protocol.

Appendices

Appendix 1. Draft strategy for MEDLINE (Ovid)

1. exp Nail Diseases/
2. exp Nails/
3. (digit or digits or thumb$ or toe$ or finger$ or toenail$ or fingernail$ or nail$1 or thumbnail$).ti,ab.
4. (subungual or ungual or ungula or periungual or ungueal or unguium).ti,ab.
5. 1 or 2 or 3 or 4
6. exp Carcinoma, Basal Cell/
7. exp Carcinoma, Squamous Cell/
8. exp Skin Neoplasms/
9. squamous cell carcinoma$.ti,ab.
10. scc.ti,ab.
11. (melanoma$ or malignan$ or cancer$ or neoplasm$ or tumor$ or tumour$ or carcinoma$).ti,ab.
12. or/6‐11
13. excision$.ti,ab.
14. exp Mohs Surgery/
15. exp dermatologic surgical procedures/
16. mohs.ti,ab.
17. digit sparing surger$.ti,ab.
18. micrographic surger$.ti,ab.
19. exp "margins of excision"/
20. surgical margin$.ti,ab.
21. exp Amputation/
22. amputat$.ti,ab.
23. terminali$.ti,ab.
24. 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23
25. 5 and 12 and 24

Contributions of authors

CMH was the contact person with the editorial base.
CMH co‐ordinated the contributions from the co‐authors and wrote the final draft of the protocol.
CMH, RGW, JNB and BS worked on the Methods section.
CMH and RGW drafted the clinical sections of the Background and responded to the clinical comments of the referees.
CMH, FE and RGW responded to the methodological and statistical comments of the referees.
CMH, RGW, JCRW, FE, JNB, DD and BS contributed to writing the protocol.
BS was the consumer co‐author and checked the protocol for readability and clarity. He also ensured that the outcomes are relevant to consumers.

Disclaimer

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to Cochrane Skin. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Sources of support

Internal sources

  • No sources of support provided

External sources

  • The National Institute for Health Research (NIHR), UK

    The NIHR, UK, is the largest single funder of Cochrane Skin.

Declarations of interest

Claire Hardie: none known.
Ryckie G Wade: none known.
Justin CR Wormald: none known.
Brian Stafford: none known.
Faye Elliott: none known.
Julia Newton‐Bishop: my institution has received a grant from Cancer Research UK to carry out research looking at melanoma survival. Daily fees were paid to me when I was Clinical Lead at the National Institute for Health and Care Excellence (NICE) for the Clinical Melanoma Guideline. I have been reimbursed for travel expenses when asked to give talks at academic meetings. None of these were paid from identifiable commercial entities; conference organisers commonly pool funding sources including commercial companies. I have done legal work for clinical negligence claims in the past and the last case is now coming to an end. These fees were primarily used to support the research group but I did receive one fee from one client personally. My research group is in receipt of a number of research grants from Cancer Research UK, the Medical Research Council, Melanoma Focus, Melanoma Research Alliance and the National Institutes of Health that are for research unrelated to this Cochrane work. A single honorarium was accepted for a talk in 2019; paid to my institution. I receive very small royalties for a textbook published many years ago. I am invited to around three meetings per year where my travel costs are paid by the conference organisers. I have not travelled to meetings where the costs are paid directly by a drug company. I have listed grants and travel expenses paid to enable me to complete my research but I do not believe that they reflect a conflict of interest with respect to this Cochrane work.
Donald Dewar: none known.

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References

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