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Squamous Cell Carcinoma: An update on Treatment and Management

Squamous Cell Carcinoma: An update on Treatment and Management. Ritu Saini, MD NY Medical Skin Solutions New York University Langone Medical Center. Epidemiology. 20% of all cutaneous cancers annually 200,000 new cases  30 00 deaths annually

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Squamous Cell Carcinoma: An update on Treatment and Management

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  1. Squamous Cell Carcinoma:An update on Treatment and Management Ritu Saini, MD NY Medical Skin Solutions New York University Langone Medical Center

  2. Epidemiology • 20% of all cutaneous cancers annually • 200,000 new cases  3000 deaths annually • Metastasis rate is 0.3-16% (mainly in high-risk SCC) • Lifetime risk • 14 % in Caucasian Males • 9% in Caucasian Females • Typical age of presentation age 70  highest incidence age 85 Holme SA et al. Br J Dermatol 2000; 143:1124-9 Veness MJ. Australian J Dermatol 2006; 47:28-33

  3. Risk Factors for Squamous Cell Cancer • Sun Exposure (pre-cancerous actinic keratosis lesions) • Chronic Wounds • Marjolin’s ulcers (burn scars/decubitii) • Diabetes • Venous disease • Arterial insufficiency • Immunopathy (organ transplants ↑14 % scc:bcc 5:1) • Other malignancies • Wound healing complications following surgery *Commonly seen in geriatric population

  4. Complete History and Physical • Etiology • Duration • Previous Treatment • History of similar wounds • Pain • History of skin cancer • Vascular • Neurological • Orthopedic

  5. Treatment • Surgery • Standard exision • Mohs surgery • Electrodessication and curettage • Cryosurgery • Topical chemotherapies (Imiquimod, Fluorouracil) • Radiation • Systemic chemotherapies (largely reserved for OTR’s) * In elderly population greater potential for developing high-risk tumors  Greater risk for metastasis

  6. High-Risk Squamous Cell carcinoma

  7. Features of High-risk SCC Jennings, L and Schmults, J Clin Aesthetic Dermatol. 2010;3(4):39–48.

  8. Tumor Location • Arising in previously injured skin • Burn site • Scar • Chronic wound • Ulcer • Ear • Lip • Anogenital • Recurrence rate of 58% • Overall 5 year survival of 52% • *9 and 14% risk of metastasis, respectively compared to other sun exposed sites • 15-74% increased risk * Rowe DE et al. J Am Acad Dermatol. 1992;26(6):976–990.

  9. Tumor Size • > 2 cm in size trunk and extremities • <2 cm in size • ≥ 1 cm – cheeks, forehead, scalp, neck ≥ 0.6 cm – “mask” or “H” area of face • Lip • Ear Higher recurrence (15% vs 7%) Metastatic rate(30% vs 9%) Review of 915 SCC risk of mets higher in tumors ≥ 1.5cm Prospective study of 266 patients with metastatic SCC, median size 1.5cm Moore BA et al. Laryngoscope. 2005; 115:1561-1567 Quaedvlig PJF et al. Histopathology. 2006

  10. Courtesy of Head and Neck Brown University, Dermatologic Surgery Dept of Univ. of Washington, South Texas Skin Cancer Center, and Medscape

  11. Histological Grade • 37% cure rate for poorly differentiated tumors • Desmoplastic (infiltrative) have high propensity for regional metastasis • 59% and 88% for moderately and well differentiated tumors, respectively • 22% vs 3.8% Lymph node metastasis • 27.4% vs. 2.6% local recurrence Mullen JT, et al. Ann Surg Oncol. 2006;13(7):902–909. Goepfert H, et al. Am J Surg. 1984;148(4):542–547.

  12. Perineural Invasion • Occurs in 7% of cutaneous SCC • High incidence of recurrence, metastasis, and death • Outcomes are worse for those with clinical symptoms of perineural invasion. • Ross et al. reported poorer outcomes for those with involvement of nerves 0.1 mm or larger (32% increased risk of death) Ross AS, Whalen FM, Elenitsas R. Dermatol Surg. 2009;35(12):1859–1866.

  13. Perineural Invasion Courtesy of Memorial Sloan Kettering

  14. Management and Treatment

  15. Staging • Regional Lymph node exam should be performed • Fine-needle aspiration or excisional biopsy for all enlarged nodes • + nodes should be resected • Adjuvant radiation  73 % five year survival

  16. Sentinel Lymph Node Biopsy: Is it warranted in the staging of high-risk squamous cell carcinoma?

  17. Sentinel Lymph Node Biopsy • Case reports and series – No controlled studies • Review of English literature • Anogenital and non-anogenital cases with clinically negative nodes analyzed separately • Percentage of (+) sentinel lymph node biopsy • False negative rates calculated • Local recurrence • Nodal and distant metastasis • Number of deaths from disease Ross AS, Schmults CD. DermatolSurg 2006; 32: 1309-1321

  18. Review of English Literature (SNLB) Anogenital Non-anogenital • 607 patients • 24% +SNLB • False Negative rate of 4% • 85 patients • 21% +SNLB • False Negative rate of 5% Controlled studies are needed to demonstrate whether early detection of subclinical nodal metastasis will lead to improved disease-free or overall survival for patients with high-risk SCC SLNB accurately diagnoses subclinical lymph node metastasis with few false-negative results and low morbidity.

  19. Imaging • Standard method to determine subnodal spread • Gold standard modality not well established in SCC • Can extrapolate using body of data from oro-nasopharyngeal tumors • Variable sensitivity and specificity for CT, MRI, PET • Survey study of 117 mohs surgeons • 35 % seldom image High-risk SCC patients • 54% - CT, 36% -MRI, 15%- PET

  20. Imaging Computed Tomography Magnetic Resonance Imaging • Central nodal necrosis • Extracapsular Spread • Skull-based Invasion • Cartilage involvement • Neurotrophic tumors (advance perineural invasion) • Defines tissue planes • Distinguishes dense connective tissue from Muscle Imaging poses little risk and can be beneficial in preoperative planning and nodal staging if extensive tissue involvement is suspected

  21. Treatment

  22. Treatment of high-risk SCC • Trunk and Extremities > 2cm (no other high risk factors) • Wide Excision with 1 cm margins • If margins negative • Follow up clinically • If margins positive • Mohs surgery for better margin control • Resection with complete circumferential peripheral and deep margin assessment with frozen or permanent sections

  23. Treatment of High-risk SCC • Head and neck tumors with Palpable regional nodes or abnormal nodes on imaging • Perform Fine Needle Aspiration (FNA) • If FNA (-) • Re-evaluate clinically • Repeat FNA • Lymph node removal • If FNA (+)  Head/neck Surgical consultation • Lymph node resection for surgical candidates • Adjuvant radiation therapy may be indicated • Radiation therapy for non-surgical candidates Practice Guidelines in Oncology – V.1. 2009 National Comprehensive Cancer Network (nccn.org

  24. Adjuvant Radiation • Recommended for high-risk SCC especially in setting of perineural invasion • Review comparing high-risk SCC treated with surgery alone vs. surgery and adjuvant radiation therapy (ART) Jambusaria-Pahlajani A et al. Dermatol Surg. 2009;35(4):574–585.

  25. Surgery vs. Surgery + ART • Primary outcomes assessed: • Local recurrences • Nodal Metastasis • Distant Metastasis • Disease-Specific Death • Methods/Subjects • No controlled studies found • 2449 cases of non-anogenital SCC • 2358 cases treated with surgery only • 91 cases treated with surgery and ART

  26. Surgery vs. Surgery + ART • ART played the greatest role in cases of perineural invasion- with size of nerve being most important • <0.1 mm in diameter • Only 5% recurrence rate (n=1/22) • No metastasis • No disease-specific death • ≥ 0.1 mm in diameter • 50% risk of local recurrence • 38% risk of regional nodal metastasis • 32% distant metastasis with disease-specific death

  27. Surgery vs. Surgery + ART • Surgery + ART • 19% regional metastasis • 13% distant metastasis • Surgery Alone • 10% regional metastasis • 4% distant metastasis • Data were not controlled for tumor stage • Likely more advanced disease • Clear surgical margins were not documented

  28. Surgery vs. Surgery + ART • Clear Surgical Margins • 943 cases – clear surgical margins documented • 5% risk local recurrence • 5% regional mets • 1% distant mets • 1% disease specific death • Outcomes significantly better than in cases (1,506) when margin status not reported

  29. Surgery vs. Surgery + ART • Conclusion • Cure rates are high when surgical margins are clear • It is not clear just which patients and to what extent they will benefit from adjuvant radiation therapy • May be indicated in certain situations • Named nerves or nerves > 0.1 mm • Uncertain or positive surgical margins • Inoperable cases • In-transit metastasis

  30. Follow Up Local Disease Regional Disease • History and Physical • Q 3-6 months for 2 years • Q 6-12 months for 3 year • Annual exam for life • History and Physical • complete skin and regional lymph node exam • Q 1-3 months for 1 year • Q 2-4 months for 2nd year • Q 4-6 months for 3rd-5th year • Q6-12 months for life Patient education Sun avoidance Sunscreens Sun protective clothing Self skin examinations

  31. Conclusions • Management of high-risk squamous cell carcinoma is complicated • Lack of prognostic and treatment guidelines make management nebulous • Best practice regimens based on retrospective studies • Controlled prospective studies needed for clarity

  32. Conclusions • Early detection • Surgical treatments with clear margins when possible • Staging of draining nodal basins • Adjuvant radiation when indicated • Close follow up

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