Systematic review evidence
What factors need to be considered when determining the optimal surgical technique for those with basal cell carcinoma?
A systematic review was undertaken to answer this clinical question. The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.
A total of 24 studies were identified that reported on outcomes of surgical treatment for basal cell carcinoma (BCC) according to various risk factors. These included one randomised controlled trial (RCT), two case control studies, one prospective cohort study, five retrospective cohort studies and 15 case series.
Surgical techniques included surgical excision, Mohs micrographic surgery (MMS), and electrodessication and curettage.
Reported outcomes included completeness of excision, recurrence rates, and cure rates.
Studies reported recurrence rates for BCC according to the following treatment-related factors:
- surgical margin (two studies)
- treatment type (six studies)
- reconstruction technique (two studies).
Studies also reported recurrence rates for BCC according to a range of tumour-related factors:
- tumour histology (five studies)
- tumour location (12 studies)
- tumour size (two studies)
- tumour infiltration depth (one study).
No RCT investigated the relationship between excision margins and recurrence rates. However, some studies found associations between recurrence rate and histologic subtype or tumour location, which suggest that wider surgical margins and more judicious follow-up may be necessary when excising BCCs with higher-risk features such as aggressive histological subtype, the presence of pigment, unfavourable anatomical sites (e.g. H-zonethe area of the face that includes the central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, and ear of the face).
Surgical margins of 3mm were used in the RCT comparing surgical excision with Mohs micrographic surgery (MMS) for BCCs of the face. For primary BCCs, this study reported 10-year recurrence rates of 4.4% after MMS and 12.2% after surgical excision (statistically nonsignificant difference).[van Loo et al 2014] All recurrences appeared on the H-zonethe area of the face that includes the central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, and ear, and a high proportion (56%) of recurrences occurred after more than 5 years.
Overall aggressive histologic subtypes were found to be more likely to recur than non-aggressive types. Tumours on the nose eyes lips and ears were more likely to recur than elsewhere on the face or body.
Based on weak evidence (small non-randomised studies with inconsistent results), completeness of excision appears to be related to tumour histology and to location.Evidence from studies examining the relationship between excision margins and recurrence rate was inconsistent and of poor quality, as was evidence from studies examining the relationship between closure technique and recurrence rate.
Evidence summary and recommendations
|Basal cell carcinoma subtypes significantly associated with recurrence were aggressive, sclerodermiform and non-pigmented subtypes as well as those with infiltrative, metatypic-basaloid squamous cell-pleomorphic patterns, compared with less aggressive, nodular, adenoid, superficial and pigmented subtypes and subtypes with pilar differentiation.||II, III-2, III-3, IV||, , , , , , , , , |
|Basal cell carcinomas on the face and H-zonethe area of the face that includes the central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, and ear of the face were generally more likely to recur after surgical excision than those on the rest of the body, forehead, cheek and temple. However, only tumours located on the nose, lips, eyes and superior eyelid were found to have significantly higher rates of recurrence than those on the forehead, check, temple, medial and lateral canthus and lower eyelid.||II, III-2, III-3, IV||, , , , , , , , |
|There were no difference in recurrence rates between surgical margins 3,4 and ≥5mm on the nose. However, excision sizes >1.75cm2 were associated with significantly higher recurrence than excision sizes <1.75cm2 on the eyelid.||IV||, |
|No significant difference was found in the mean size of tumours which did and did not recur.||II, III-3||, |
|BCCs that had invaded deep structures were more likely to recur than BCCs that had invaded into the reticular dermis, hypodermis and papillary dermis.||IV|||
|Incomplete excision was generally found to be greater on the face and head than the rest of the body (trunk, legs and arms), and on the nose, eyelid and ears than the rest of the face and head.||III-2, III-3, IV||, , , , , , |
| Rates of incomplete excisions were found to be higher with undefined and mixed histology, fibrosing, adenoid, and non-pigmented BCCs than pigmented and superficial BCCs.
Rates of incomplete excision for nodular and infiltrative BCCs were mixed.
No significant difference in rates of incomplete excision was found between groups with some aggressive types of BCC (morpheaform [sclerosingscar-like (morphoeic)], infiltrative, nodulo-infiltrative) and non-aggressive (nodular, superficial, pagetoid) BCCs.
|III-2, III-3, IV||, , , , , |
| There was no significant association between completeness of excision for BCCs when comparing margin widths of ≤2mm, 3mm, 4mm, and ≥5mm.
There was no significant association between completeness of excision comparing BCCs excised with 2mm and 4mm margins versus inspected healthy margins.
Numerically higher rates of complete excision were reported for BCCs with 4-mm margins versus 3-mm and 5-mm margins, but these results were not statistically analysed.
|III-2, IV||, , , |
|BCCs that stopped before the reticular dermis had significantly higher rates of complete excision than those that had spread to the hypodermis, muscle, cartilage, bone and nerve.||III-3|||
|There was no significant associated between mean diameter of tumours which were completely excised versus incompletely excised. However tumour size >3cm was associated with more complete excisions than <0.5cm.||III-2, III-3||, |
|The 5-year cure rate was over 97% for BCCs surgically excised on the face in areas such as the nose, eyelid, temple, forehead, and cheek.||IV||, |
|EBR 7.3.1. Patients with high-risk recurrent facial basal cell carcinomas should be offered wide surgical excision or Mohs micrographic surgery. Regular follow-up should be provided.||C|
|EBR 7.3.2. Non-surgical treatment modalities can be considered for patients with basal cell carcinomas assessed to have a low risk of recurrence based on favourable histological type (e.g. superficial or nodular types) and favourable anatomic locations (away from unique structures).||C|
Notes on the recommendations
Follow-up of patients after treatment is individually tailored according to patient factors, tumour factors, anatomic site and the perceived adequacy of treatment.
Current literature supports the use of wide surgical excision or Mohs surgery for primary high-risk facial BCCs. The RCT reported no significant difference between 10-year recurrence rates for primary BCCs treated by MMS or surgical excision. For recurrent BCCs, however, MMS achieved higher 10-year cure rates than surgical excision.
Recent US guidelines for the management of BCC[Bichakjian et al 2018] recommend surgical excision for low-risk primary BCCs and selected high-risk BCCs, but make a stronger recommendation for MMS in high-risk tumours (defined according to National Comprehensive Cancer Network stratification[ref] to include all H-zonethe area of the face that includes the central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, and ear facial tumours as well as tumours that are large, poorly defined, recurrent, showing aggressive growth pattern or perineural invasion, at radiation therapy sites, or in immunosuppressed patients). The US working group based its recommendation for MMS in both primary and recurrent BCC mainly on the only available RCT, but noted that ‘these findings cannot necessarily be extrapolated beyond the scope of the study population with facial BCC.’ The US working group further noted that the lack of availability of tissue blocks for molecular testing or further histological examination is a limitation of MMS, and suggested that this limitation should be minimised by careful selection of MMS candidates based on initial biopsy results.
Our recommendation was made after considering these same limitations, as well as the availability of MMS in Australia. MMS has a statistically significant advantage for high risk recurrent facial BCC, but not for primary at this stage.
- Surgical treatment – Introduction
- Considerations before selecting a surgical treatment modality
- Optimal primary excision techniques:
- Post-surgical care and interpretation of the pathology report
- Protocol to manage incompletely resected basal cell carcinoma
- Protocol to manage rapidly growing tumours
- Criteria for choosing Mohs micrographic surgery in preference to other surgical techniques
- Surgical management of advanced cutaneous squamous cell carcinoma
- Surgical treatment – Health system implications and discussion
|PICO question SX2||Evidence statement form SX2||Systematic review report SX2|
- Mosterd K, Krekels GA, Nieman FH, Ostertag JU, Essers BA, Dirksen CD, et al. Surgical excision versus Mohs' micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years' follow-up. Lancet Oncol 2008 Dec;9(12):1149-56 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19010733.
- van Loo E, Mosterd K, Krekels GA, Roozeboom MH, Ostertag JU, Dirksen CD, et al. Surgical excision versus Mohs' micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10 year follow-up. Eur J Cancer 2014 Nov;50(17):3011-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25262378.
- Mueller CK, Nicolaus K, Thorwarth M, Schultze-Mosgau S. Multivariate analysis of the influence of patient-, tumor-, and management-related factors on the outcome of surgical therapy for facial basal-cell carcinoma. Oral Maxillofac Surg 2010 Sep;14(3):163-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20349095.
- Unlü RE, Altun S, Kerem M, Koç MN. Is it really necessary to make wide excisions for basal cell carcinoma treatment? J Craniofac Surg 2009 Nov;20(6):1989-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19881375.
- Chren MM, Torres JS, Stuart SE, Bertenthal D, Labrador RJ, Boscardin WJ. Recurrence after treatment of nonmelanoma skin cancer: a prospective cohort study. Arch Dermatol 2011 May;147(5):540-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21576572.
- Chren MM, Linos E, Torres JS, Stuart SE, Parvataneni R, Boscardin WJ. Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2013 May;133(5):1188-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23190903.
- Stuart SE, Schoen P, Jin C, Parvataneni R, Arron S, Linos E, et al. Tumor recurrence of keratinocyte carcinomas judged appropriate for Mohs micrographic surgery using Appropriate Use Criteria. J Am Acad Dermatol 2017 Jun;76(6):1131-1138.e1 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28365039.
- Armstrong LTD, Magnusson MR, Guppy MPB. Risk factors for recurrence of facial basal cell carcinoma after surgical excision: A follow-up analysis. J Plast Reconstr Aesthet Surg 2017 Dec;70(12):1738-1745 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28579037.
- Codazzi D, Van Der Velden J, Carminati M, Bruschi S, Bocchiotti MA, Di Serio C, et al. Positive compared with negative margins in a single-centre retrospective study on 3957 consecutive excisions of basal cell carcinomas. Associated risk factors and preferred surgical management. J Plast Surg Hand Surg 2014 Feb;48(1):38-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23731130.
- Goto M, Kai Y, Arakawa S, Oishi M, Ishikawa K, Anzai S, et al. Analysis of 256 cases of basal cell carcinoma after either one-step or two-step surgery in a Japanese institution. J Dermatol 2012 Jan;39(1):68-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21951151.
- Pereira CT, Kruger EA, Sayer G, Kim J, Hu J, Miller TA, et al. Mohs versus surgical excision in nonmelanoma skin cancers: does location matter? Ann Plast Surg 2013 Apr;70(4):432-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23486132.
- van der Eerden PA, Prins ME, Lohuis PJ, Balm FA, Vuyk HD. Eighteen years of experience in Mohs micrographic surgery and conventional excision for nonmelanoma skin cancer treated by a single facial plastic surgeon and pathologist. Laryngoscope 2010 Dec;120(12):2378-84 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21046543.
- de Godoy CAP, de Oliveira Neta AL, de Souza Leão SS, Lima Dantas R, Carvalho VOF, Freire da Silva S. Evaluation of surgical margins according to the histological type of basal cell carcinoma*. An. Bras. Dermatol. 2017 [cited 2018 Apr 3] Abstract available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429110/.
- Demirseren DD, Ceran C, Aksam B, Demirseren ME, Metin A. Basal cell carcinoma of the head and neck region: a retrospective analysis of completely excised 331 cases. J Skin Cancer 2014;2014:858636 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24864212.
- Fatigato G, Capitani S, Milani D, Grassilli S, Alameen AA, Candiani M, et al. Risk factors associated with relapse of eyelid basal cell carcinoma: results from a retrospective study of 142 patients. Eur J Dermatol 2017 Aug 1;27(4):363-368 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28524055.
- Hansen C, Wilkinson D, Hansen M, Soyer HP. Factors contributing to incomplete excision of nonmelanoma skin cancer by Australian general practitioners. Arch Dermatol 2009 Nov;145(11):1253-60 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19917954.
- Ito Y, Kurata M, Hioki R, Suzuki K, Ochiai J, Aoki K. Cancer mortality and serum levels of carotenoids, retinol, and tocopherol: a population-based follow-up study of inhabitants of a rural area of Japan. Asian Pac J Cancer Prev 2005 Jan;6(1):10-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15780024.
- Konopnicki S, Hermeziu O, Bosc R, Abd Alsamad I, Meningaud JP. Nasal basal cell carcinomas. Can we reduce surgical margins to 3mm with complete excision? Ann Chir Plast Esthet 2016 Aug;61(4):241-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26879668.
- Lawrence CM, Haniffa M, Dahl MG. Formalin-fixed tissue Mohs surgery (slow Mohs) for basal cell carcinoma: 5-year follow-up data. Br J Dermatol 2009 Mar;160(3):573-80 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19210500.
- Levin F, Khalil M, McCormick SA, Della Rocca D, Maher E, Della Rocca RC. Excision of periocular basal cell carcinoma with stereoscopic microdissection of surgical margins for frozen-section control: report of 200 cases. Arch Ophthalmol 2009 Aug;127(8):1011-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19667338.
- Lin SH, Cheng YW, Yang YC, Ho JC, Lee CH. Treatment of Pigmented Basal Cell Carcinoma with 3 mm Surgical Margin in Asians. Biomed Res Int 2016;2016:7682917 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27652267.
- Malik V, Goh KS, Leong S, Tan A, Downey D, O'Donovan D. Risk and outcome analysis of 1832 consecutively excised basal cell carcinomas in a tertiary referral plastic surgery unit. J Plast Reconstr Aesthet Surg 2010 Dec;63(12):2057-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20226750.
- Paoli J, Daryoni S, Wennberg AM, Mölne L, Gillstedt M, Miocic M, et al. 5-year recurrence rates of Mohs micrographic surgery for aggressive and recurrent facial basal cell carcinoma. Acta Derm Venereol 2011 Oct;91(6):689-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21681360.
- Pua VS, Huilgol S, Hill D. Evaluation of the treatment of non-melanoma skin cancers by surgical excision. Australas J Dermatol 2009 Aug;50(3):171-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19659977.
- Sartore L, Lancerotto L, Salmaso M, Giatsidis G, Paccagnella O, Alaibac M, et al. Facial basal cell carcinoma: analysis of recurrence and follow-up strategies. Oncol Rep 2011 Dec;26(6):1423-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21922143.
- Ullah H, Tahir M, Khan M, Naz S. Frequency of incomplete excision of low risk facial basal cell carcinoma with a safety margin of three millimetre. Pakistan Journal Of Surgery Abstract available at http://www.pjs.com.pk/journal_pdfs/jan_mar18/72.pdf.
- Wetzig T, Woitek M, Eichhorn K, Simon JC, Paasch U. Surgical excision of basal cell carcinoma with complete margin control: outcome at 5-year follow-up. Dermatology 2010;220(4):363-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20484877.