Keratinocyte cancer

7.4 Considerations when planning surgical treatment for cutaneous squamous cell carcinoma

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Systematic review evidence[edit source]

In patients undergoing surgical treatment for cutaneous squamous cell carcinoma, which surgery-related factors (margin width, depth of excision) or tumour-related factors (size, histological features, anatomical site) influence clinical outcomes (cure rate, local recurrence, regional lymph node involvement, metastasis)?

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.

Fourteen studies were identified that reported outcomes of surgical treatment for cSCCs based on various risk factors. These included three case control studies[1][2][3] and 11 case series.[4][5][6][7][8][9][10][11][12][13][14] There were no randomised controlled trials (RCTs).

Two case series had a moderate risk of bias[4][6] and the remainder of studies all had a high risk of bias.

Surgical techniques included excision, Mohs micrographic surgery (MMS), biopsy and lymph node dissection.

Reported outcomes included local recurrence, regional recurrence, metastasis and death.

No studies were identified that examined the influence of surgical technique of other surgery-related factors on clinical cancer outcomes.

Studies reported recurrence rates according to a range of tumour-related factors:

Only one study reported recurrence rate according to surgical margin.[10]

Studies reported rates of metastasis according to a range of tumour-related factors:

Overall, aggressive histologic subtypes (spindle cell, poorly differentiated, fibrosing) and large tumours were found to be more likely to recur or metastasise than non-aggressive types or smaller tumours.[1][2][3][4][5][6][7][8][9][11]

Evidence for an association between anatomical site and risk of recurrence or metastasis was less certain, with no significant differences reported.[3][4][6][8][9][11][12][13] Variation in surgical technique and competence may be a confounding factor influencing the relationship between anatomical site and risk.

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Evidence summary and recommendations[edit source]

Evidence summary Level References
Anatomical site

Two studies found there was no statistically significant correlation between recurrence and the site of the excised cSCC, while the other studies did not test for significance.

IV [4], [8], [9], [12], [14]
Histology: fibrosing (‘desmoplastic’)

One study found that desmoplasia (desmoplastic cSCCs compared with non-desmoplastic cSCCs) was a significant risk factor for recurrence.

IV [4]
Histology: poorly differentiated/spindle cell carcinoma

Two out of three studies found a significant association between poorly differentiated cSCCs and recurrence, while one found no correlation.

IV [4], [5]
Tumour size (diameter)

Two studies observed that tumours <20mm recurred less than tumours ≥20 mm (although one study observed no recurrence among tumours >40 mm). Neither study performed statistical analysis.

Another study reported that tumour diameter >20 mm (compared with ≤20 mm) was associated with a significantly higher risk of recurrence after excision on univariate analysis, but not on multivariate analysis when other factors (e.g. tumour thickness, number of SCCs, anatomical site and immune status) were considered.

IV [4], [9], [11]
Surgical margin

Only one study reported on recurrence based on surgical excision margins but did not test their results for significance.

IV [10]
Anatomical site

There was inconsistent evidence on the relationship between risk of metastasis and the anatomical site of the excised SCC.

IV, III-3 [3], [4], [6], [8], [9], [11], [12], [13]
Histology: fibrosing (‘desmoplastic’)

One study found desmoplastic cSCCs were significantly more likely to metastasise than non-desmoplastic cSCCs.

IV [4]
Histology: poorly differentiated/spindle cell carcinoma

The evidence for the relationship between risk of metastasis and histological finding of tumour differentiation/spindle cell carcinomas was mostly consistent; poorly differentiated SCCs metastasised more (7% to 82%) than well differentiated SCCs (0% to 56%), although only one study reported outcomes based on spindle cell carcinoma.

IV, III-3 [1], [3], [4], [5], [6], [7], [8], [9], [11]
Tumour size (diameter)

The studies almost consistently found that larger (≥20mm in diameter) tumours had higher rates of metastasis (12% to 57%) than small (<20mm in diameter) tumours (0% to 19%).

IV, III-3 [2], [4], [6], [9], [11]

Practice pointQuestion mark transparent.png

PP 7.4.1. Referral to a multidisciplinary team or to a specialist for assessment and treatment should be considered for patients with cutaneous squamous cell carcinomas with poor prognostic features (e.g. poorly differentiated, fibrosing or ≥20mm).

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Notes on these recommendations[edit source]

There is insufficient evidence on which to base evidence-based recommendations.

Reported associations between recurrence rate, metastases and histologic subtype suggest that wider surgical margins and more judicious follow-up may be necessary in the surgical treatment of SCCs with high-risk features.

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Appendices[edit source]

Jutta's magnifying glass icon.png PICO question SX3 View Evidence statement form SX3 Evidence statement form SX3 View Systematic review report SX3Systematic review report SX3

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References[edit source]

  1. 1.0 1.1 1.2 1.3 1.4 Jensen V, Prasad AR, Smith A, Raju M, Wendel CS, Schmelz M, et al. Prognostic criteria for squamous cell cancer of the skin. J Surg Res 2010 Mar;159(1):509-16 Available from:
  2. 2.0 2.1 2.2 2.3 Peat B, Insull P, Ayers R. Risk stratification for metastasis from cutaneous squamous cell carcinoma of the head and neck. ANZ J Surg 2012 Apr;82(4):230-3 Available from:
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Toll A, Gimeno-Beltrán J, Ferrandiz-Pulido C, Masferrer E, Yébenes M, Jucglà A, et al. D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: a marker of metastatic risk. J Am Acad Dermatol 2012 Dec;67(6):1310-8 Available from:
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008 Aug;9(8):713-20 Available from:
  5. 5.0 5.1 5.2 5.3 5.4 5.5 Brinkman JN, Hajder E, van der Holt B, Den Bakker MA, Hovius SE, Mureau MA. The Effect of Differentiation Grade of Cutaneous Squamous Cell Carcinoma on Excision Margins, Local Recurrence, Metastasis, and Patient Survival: A Retrospective Follow-Up Study. Ann Plast Surg 2015 Sep;75(3):323-6 Available from:
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 2012 Dec;106(7):811-5 Available from:
  7. 7.0 7.1 7.2 7.3 Clark RR, Soutar DS, Hunter KD. A retrospective analysis of histological prognostic factors for the development of lymph node metastases from auricular squamous cell carcinoma. Histopathology 2010 Jul;57(1):138-46 Available from:
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 Dormand EL, Ridha H, Vesely MJ. Long-term outcome of squamous cell carcinoma of the upper and lower limbs. J Plast Reconstr Aesthet Surg 2010 Oct;63(10):1705-11 Available from:
  9. 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 Hutting KH, Bos PG, Kibbelaar RE, Veeger NJGM, Marck KW, Mouës CM. Effective excision of cutaneous squamous cell carcinoma of the face using analysis of intra-operative frozen sections from the whole specimen. J Surg Oncol 2018 Mar;117(3):473-478 Available from:
  10. 10.0 10.1 10.2 Jenkins G, Smith AB, Kanatas AN, Houghton DR, Telfer MR. Anatomical restrictions in the surgical excision of scalp squamous cell carcinomas: does this affect local recurrence and regional nodal metastases? Int J Oral Maxillofac Surg 2014 Feb;43(2):142-6 Available from:
  11. 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 Krediet JT, Beyer M, Lenz K, Ulrich C, Lange-Asschenfeldt B, Stockfleth E, et al. Sentinel lymph node biopsy and risk factors for predicting metastasis in cutaneous squamous cell carcinoma. Br J Dermatol 2015 Apr;172(4):1029-36 Available from:
  12. 12.0 12.1 12.2 12.3 12.4 12.5 Roozeboom MH, Lohman BG, Westers-Attema A, Nelemans PJ, Botterweck AA, van Marion AM, et al. Clinical and histological prognostic factors for local recurrence and metastasis of cutaneous squamous cell carcinoma: analysis of a defined population. Acta Derm Venereol 2013 Jul 6;93(4):417-21 Available from:
  13. 13.0 13.1 13.2 13.3 Szewczyk M, Pazdrowski J, Golusiński P, Dańczak-Pazdrowska A, Marszałek S, Golusiński W. Analysis of selected risk factors for nodal metastases in head and neck cutaneous squamous cell carcinoma. Eur Arch Otorhinolaryngol 2015 Oct;272(10):3007-12 Available from:
  14. 14.0 14.1 14.2 14.3 Vasconcelos L, Melo JC, Miot HA, Marques ME, Abbade LP. Invasive head and neck cutaneous squamous cell carcinoma: clinical and histopathological characteristics, frequency of local recurrence and metastasis. An Bras Dermatol 2014 Jul;89(4):562-8 Available from:

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