Ritu Saini, MDNY Medical Skin Solutions

New York University Langone Medical Center

Epidemiology20% 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 Males9% in Caucasian Females

Typical age of presentation age 70 highest incidence age 85

Holme SA et al. Br J Dermatol 2000; 143:1124-9Veness MJ. Australian J Dermatol 2006; 47:28-33

Risk Factors for Squamous Cell Cancer

Sun Exposure (pre-cancerous actinic keratosis lesions)

Chronic WoundsMarjolin’s ulcers (burn scars/decubitii) Diabetes Venous diseaseArterial insufficiencyImmunopathy (organ transplants ↑ 14 % scc:bcc 5:1)Other malignanciesWound healing complications following surgery*Commonly seen in geriatric population

Complete History and PhysicalEtiology DurationPrevious TreatmentHistory of similar woundsPainHistory of skin cancerVascularNeurologicalOrthopedic

TreatmentSurgery

Standard exisionMohs surgery

Electrodessication and curettageCryosurgeryTopical chemotherapies (Imiquimod, Fluorouracil)RadiationSystemic chemotherapies (largely reserved for

OTR’s)* In elderly population greater potential for

developing high-risk tumors Greater risk for metastasis

Features of High-risk SCC

Jennings, L and Schmults, J Clin Aesthetic Dermatol. 2010;3(4):39–48.

Tumor LocationArising in previously

injured skinBurn siteScar Chronic woundUlcer

EarLipAnogenital

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> 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 1.5cmMoore BA et al. Laryngoscope. 2005; Moore BA et al. Laryngoscope. 2005;

115:1561-1567 115:1561-1567 Quaedvlig PJF et al. Histopathology. 2006Quaedvlig 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 Grade37% 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 InvasionOccurs in 7% of cutaneous SCCHigh 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

StagingRegional 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

Is it warranted in the staging of high-risk squamous cell carcinoma?

Sentinel Lymph Node BiopsyCase reports and series – No controlled

studiesReview of English literature

Anogenital and non-anogenital cases with clinically negative nodes analyzed separately

Percentage of (+) sentinel lymph node biopsyFalse negative rates calculatedLocal recurrenceNodal and distant metastasisNumber 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%

SLNB accurately diagnoses subclinical lymph node metastasis with few false-

negative results and low morbidity.

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

ImagingStandard method to determine subnodal

spreadGold standard modality not well established in

SCCCan extrapolate using body of data from oro-

nasopharyngeal tumorsVariable sensitivity and specificity for CT, MRI,

PETSurvey study of 117 mohs surgeons

35 % seldom image High-risk SCC patients 54% - CT, 36% -MRI, 15%- PET

ImagingComputed Tomography Magnetic Resonance

ImagingCentral 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 of high-risk SCCTrunk and Extremities > 2cm (no other high

risk factors)Wide Excision with 1 cm marginsIf margins negative

Follow up clinicallyIf margins positiveIf margins positive

Mohs surgery for better margin controlMohs surgery for better margin control Resection with complete circumferential peripheral Resection with complete circumferential peripheral

and deep margin assessment with frozen or and deep margin assessment with frozen or permanent sectionspermanent sections

Treatment of High-risk SCCHead 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 RadiationRecommended 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 + ARTPrimary outcomes assessed:

Local recurrencesNodal MetastasisDistant MetastasisDisease-Specific Death

Methods/SubjectsNo controlled studies found2449 cases of non-anogenital SCC

2358 cases treated with surgery only 91 cases treated with surgery and ART

Surgery vs. Surgery + ARTART 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 + ARTSurgery + ART

19% regional metastasis13% distant metastasis

Surgery Alone10% regional metastasis4% distant metastasis

• Data were not controlled for tumor stage• Likely more advanced disease• Clear surgical margins were not documented

Surgery vs. Surgery + ARTClear Surgical Margins943 cases – clear surgical margins

documented5% risk local recurrence5% regional mets1% distant mets1% disease specific death

Outcomes significantly better than in cases (1,506) when margin status not reported

Surgery vs. Surgery + ARTConclusion

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 UpLocal Disease Regional Disease

History and PhysicalHistory and Physical

Q 3-6 months for 2 yearsQ 3-6 months for 2 years

Q 6-12 months for 3 Q 6-12 months for 3 yearyear

Annual exam for lifeAnnual exam for life

History and PhysicalHistory and Physical complete skin and complete skin and

regional lymph node examregional lymph node exam

Q 1-3 months for 1 yearQ 1-3 months for 1 year

Q 2-4 months for 2nd yearQ 2-4 months for 2nd year

Q 4-6 months for 3rd-5th Q 4-6 months for 3rd-5th yearyear

Q6-12 months for lifeQ6-12 months for life

Patient education Sun avoidance

SunscreensSun protective clothing Self skin examinations

ConclusionsManagement 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

ConclusionsEarly detection

Surgical treatments with clear margins when possible

Staging of draining nodal basins

Adjuvant radiation when indicated

Close follow up