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Review

Risk Factors and Diagnosis of Advanced Cutaneous Squamous Cell Carcinoma

Author Affiliation(s)

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer affecting humans. The combination of the increasing incidence and high mortality in advanced stages of the disease, defines cSCC as an emerging public health problem. Advanced disease includes metastatic and locally advanced cSCC. Metastatic disease refers to the presence of locoregional metastasis (in transit or to regional lymph nodes) or distant metastasis. Locally advanced disease has been defined as non-metastatic cSCC that is unlikely to be cured with surgery, radiotherapy, or combination treatment. While metastatic cSCC is easily diagnosed, locally advanced disease lacks consensus definition and diagnosis is made after multidisciplinary board consultation. Identifying patients with aggressive cSCC at highest risk for relapse may prevent the occurrence of advanced disease. Prognostic factors suggested by most guidelines include tumor diameter (>2 cm), localization on temple/ear/lip/area, thickness (>6 mm), or invasion beyond subcutaneous fat, poor grade of differentiation, desmoplasia, perineural invasion, bone erosion, immunosuppression, undefined borders, recurrence, growth rate, site of prior radiotherapy, and lymphatic or vascular involvement. Although risk factors associated with worse outcomes are well known, there is still a gap of knowledge on the precise risk of each factor taken individually. The aim of this review is to summarize cSCC prognostic factors and encompass the various staging systems to guide management and follow-up in cSCC patients at higher risk for local recurrence and metastasis. Finally, we describe the hallmarks of the advanced disease. Advanced cSCC diagnosis should be made by a multidisciplinary board considering patients’ performance status and disease characteristics

Keywords : advanced cutaneous squamous cell carcinoma, risk factors, prognostic factors, recurrence, metastasis

References

Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatology. 2015;151(10):1081–6. DOI: 10.1001/jamadermatol.2015.1187.PMID: 25928283. 2. Muzic JG, Schmitt AR, Wright AC, Alniemi DT, Zubair AS, Olazagasti Lourido JM, et al. Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma. Mayo Clin Proc. 2017;92(6):890–8. DOI: 10.1016/j.mayocp.2017.02.015. PMID: 28522111 3. Hillen U, Leiter U, Haase S, Kaufmann R, Becker J, Gutzmer R, et al. Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns—Results of a non-interventional study of the DeCOG. Eur J Cancer. 2018;96:34–43. DOI: 10.1016/j.ejca.2018.01.075. 4. 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;9(8):713–20. DOI: 10.1016/S1470-2045(08)70178-5. PMID: 18617440. 5. Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: A 10-year, single-institution cohort study. JAMA Dermatology. 2013;149(5):541–7. DOI: 10.1001/jamadermatol.2013.2139. PMID: 23677079. 6. Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer. 2020;128:60–82. DOI: 10.1016/j.ejca.2020.01.007. PMID: 32113941. 7. Murphy GF, Beer TW, Cerio R. et al. Squamous cell carcinoma. In: Elder DE, Massi D, Scolyer RA, Willemze R eds. WHO Classification of Tumours, 4th Edition. Lyon:IARC; 2018: 35-45. 8. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM ML. AJCC cancer staging manual. Eighth Edition. Switzerland: Springer; 2017. 171–81. 9. Brierley JD, Gospodarowicz MK WCU for ICC. TNM Classification of Malignant Tumours Eighth Edition. Oxford: WILEY Blackwell; 2017. 131–138. 10. Keohane SG, Proby CM, Newlands C, Motley RJ, Nasr I, Mohd Mustapa MF, et al. The new 8th edition of TNM staging and its implications for skin cancer: a review by the British Association of Dermatologists and the Royal College of Pathologists, U.K. Br J Dermatol. 2018;179(4):824–8. DOI: 10.1111/bjd.16892. 11. Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, Hwang W-T, Gelfand JM, Whalen FM, et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatology. 2013;149(4):402–10. DOI: 10.1001/jamadermatol.2013.2456. PMID: 23325457. 12. Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment. Eur J Cancer. 2020;128:83–102. DOI:10.1016/j.ejca.2020.01.008. PMID: 32113942. 13. NCCN. Squamous cell skin cancer Version 1.2021. Medlin Med Encycl. 2021; Accessed July 13, 2021. https://www.nlm.nih.gov/medlineplus/ency/article/000829.htm 14. Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk Factors for Cutaneous Squamous Cell Carcinoma Recurrence, Metastasis, and Disease-Specific Death: A Systematic Review and Meta-analysis. JAMA dermatology. 2016;152(4):419–28. DOI: 10.1001/jamadermatol.2015.4994 . PMID: 26762219. 15. Karia PS, Morgan FC, Califano JA, Schmults CD. Comparison of Tumor Classifications for Cutaneous Squamous Cell Carcinoma of the Head and Neck in the 7th vs 8th Edition of the AJCC Cancer Staging Manual. JAMA dermatology. 2018;154(2):175–81. DOI: 10.1001/jamadermatol.2017.3960. PMID: 29261835. 16. Trosman SJ, Zhu A, Nicolli EA, Leibowitz JM, Sargi ZB. High-Risk Cutaneous Squamous Cell Cancer of the Head and Neck: Risk Factors for Recurrence and Impact of Adjuvant Treatment. Laryngoscope. 2021;131(1):E136–43. DOI: 10.1002/lary.28564. PMID: 32065413. 17. Wang DM, Kraft S, Rohani P, Murphy GF, Besaw RJ, Karia PS, et al. Association of nodal metastasis and mortality with vermilion vs cutaneous lip location in cutaneous squamous cell carcinoma of the lip. JAMA Dermatology. 2018;154(6):701–7. DOI: 10.1001/jamadermatol.2018.0792. PMID: 29801066. 18. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. DOI: 10.3322/caac.21388. PMID: 28094848. 19. Erkan S, Savundra JM, Wood B, Acharya AN, Rajan GP. Clinical perineural invasion of the trigeminal and facial nerves in cutaneous head and neck squamous cell carcinoma: Outcomes and prognostic implications of multimodality and salvage treatment. Head Neck. 2017;39(7):1280–6. DOI: 10.1002/hed.24607. PMID: 28474414. 20. Harris BN, Pipkorn P, Nguyen KNB, Jackson RS, Rao S, Moore MG, et al. Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck. JAMA Otolaryngol Head Neck Surg. 2019;145(2):153–8. DOI: 10.1001/jamaoto.2018.3650. PMID: 30570645. 21. Broders A. Squamous cell cancer of the lip: a study of five hundred and thirty‐seven cases. JAMA Dermatology. 1920;74:656‐664. DOI: 10.1001/jama.1920.02620100016007. 22. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):237–47. DOI: 10.1016/j.jaad.2017.08.059. DOI: 10.1016/j.jaad.2017.08.059. PMID: 29332704. 23. Breuninger H, Schaumburg-Lever G, Holzschuh J, Horny HP. Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly malignant subtype of skin cancer. Cancer. 1997 ;79(5):915–9. DOI: 10.1002/(sici)1097-0142(19970301)79:5<915::aid-cncr7>3.0.co;2-a. PMID: 9041153. 24. Cañueto J, Martín-Vallejo J, Cardeñoso-Álvarez E, Fernández-López E, Pérez-Losada J, Román-Curto C. Rapid growth rate is associated with poor prognosis in cutaneous squamous cell carcinoma. Clin Exp Dermatol. 2018;43(8):876–82. DOI: 10.1111/ced.13570. PMID: 29756221. 25. Harris BN, Bayoumi A, Rao S, Moore MG, Farwell DG, Bewley AF. Factors Associated with Recurrence and Regional Adenopathy for Head and Neck Cutaneous Squamous Cell Carcinoma. Otolaryngol neck Surg Off J Am Acad Otolaryngol Neck Surg. 2017;156(5):863–9. DOI: 10.1177/0194599817697053. PMID: 28322123. 26. Rowe DE, Carroll RJ, Day CLJ. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. 1992;26(6):976–90. DOI: 10.1016/0190-9622(92)70144-5. PMID: 1607418. 27. Manyam B V, Gastman B, Zhang AY, Reddy CA, Burkey BB, Scharpf J, et al. Inferior outcomes in immunosuppressed patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with surgery and radiation therapy. J Am Acad Dermatol. 2015;73(2):221–7. DOI: 10.1016/j.jaad.2015.04.037. PMID: 26028524. 28. Garrett GL, Blanc PD, Boscardin J, Lloyd AA, Ahmed RL, Anthony T, et al. Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States. JAMA dermatology. 2017;153(3):296–303. DOI: 10.1001/jamadermatol.2016.4920. PMID: 28097368. 29. Xu MJ, Lazar AA, Garsa AA, Arron ST, Ryan WR, El-Sayed IH, et al. Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy. Head Neck. 2018;40(7):1406–14. DOI: 10.1002/hed.25114. PMID: 29524273. 30. Migden MR, Khushalani NI, Chang ALS, Lewis KD, Schmults CD, Hernandez-Aya L, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020;21(2):294–305. DOI: 10.1016/S1470-2045(19)30728-4. PMID: 31952975. 31. Eigentler TK, Leiter U, Häfner HM, Garbe C, Röcken M, Breuninger H. Survival of Patients with Cutaneous Squamous Cell Carcinoma: Results of a Prospective Cohort Study. J Invest Dermatol. 2017;137(11):2309–15. DOI: 10.1016/j.jid.2017.06.025. PMID: 28736229. 32. Deilhes F, Boulinguez S, Pagès C, Paul C, Meyer N. Advanced Cutaneous Squamous Cell Carcinoma Is Associated with Suboptimal Initial Management in a Cohort of 109 Patients. Dermatology. 2019;235(6):516–21. DOI: 10.1159/000500636.

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