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 % (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 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

7. High-Risk Squamous Cell carcinoma

8. 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.

9. 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.

10. 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:
Quaedvlig PJF et al. Histopathology. 2006

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

12. 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.

13. 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.

14. Perineural Invasion
Courtesy of Memorial Sloan Kettering

16. Management and Treatment

17. 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

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

19. 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:

20. 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.

21. 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

22. 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

24. Treatment

25. 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

26. 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 National Comprehensive Cancer Network (nccn.org

27. 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.

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

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