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  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

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

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

Treatment Surgery Electrodessication and curettage Cryosurgery 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

High-Risk Squamous Cell carcinoma

Features of High-risk SCC When suspect high risk SCC- consider doing punch biopsy to determine depth Jennings, L and Schmults, J Clin Aesthetic Dermatol. 2010;3(4):39–48.

Tumor Location Arising in previously injured skin Ear Lip Anogenital 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.

Tumor Size ≥ 0.6 cm – “mask” or “H” area of face > 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

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

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.

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.

Perineural Invasion Courtesy of Memorial Sloan Kettering

Management and Treatment

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

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

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. Dermatol Surg 2006; 32: 1309-1321

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.

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

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

Treatment

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

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

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.

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

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

Surgery vs. 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

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

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

Follow Up Patient education Sun avoidance Sunscreens Local Disease Regional Disease 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 History and Physical Q 3-6 months for 2 years Q 6-12 months for 3 year Annual exam for life Patient education Sun avoidance Sunscreens Sun protective clothing Self skin examinations

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

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