Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.
Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.
Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines™ is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way.
© National Comprehensive Cancer Network, Inc. 2010, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.
At the beginning of each NCCN Guidelines panel meeting, panel members disclosed any financial support they have received from industry. Through 2008, this information was published in an aggregate statement in JNCCN and online. Furthering NCCN's commitment to public transparency, this disclosure process has now been expanded by listing all potential conflicts of interest respective to each individual expert panel member.
Individual disclosures for the NCCN Guidelines on Basal Cell and Squamous Cell Skin Cancers panel members can be found on page 864. (The most recent version of these guidelines and accompanying disclosures, including levels of compensation, are available on the NCCN Web site at www.NCCN.org.)
These guidelines are also available on the Internet. For the latest update, please visit www.NCCN.org.
Christenson LJ, Borrowman TA, Vachon CM et al.. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 2005;294:681–690.
Chen JG, Fleischer AB Jr, Smith ED et al.. Cost of nonmelanoma skin cancer treatment in the United States. Dermatol Surg 2001;27:1035–1038.
Weinstock MA. Epidemiology of ultraviolet radiation. In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:121–128.
Perkins JL, Liu Y, Mitby PA et al.. Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2005;23:3733–3741.
Miller SJ, Moresi JM. Actinic keratosis, basal cell carcinoma and squamous cell carcinoma. In: Bolognia J, Jorizzo JL, Rapini RV, Horn T, eds. Dermatology. London: Harcourt Health Sciences Publishers; 2003.
Rhodes AR. Public education and cancer of the skin. What do people need to know about melanoma and nonmelanoma skin cancer? Cancer 1995;75:613–636.
Clowers-Webb HE, Christenson LJ, Phillips PK et al.. Educational outcomes regarding skin cancer in organ transplant recipients: randomized intervention of intensive vs standard education. Arch Dermatol 2006;142:712–718.
Gailani MR, Bale AE. Developmental genes and cancer: role of patched in basal cell carcinoma of the skin. J Natl Cancer Inst 1997;89:1103–1109.
Brash DE, Rudolph JA, Simon JA et al.. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A 1991;88:10124–10128.
Nagano T, Ueda M, Ichihashi M. Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis. Arch Dermatol 1993;129:1157–1161.
Bale AE. Molecular genetics (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:586–591.
Rees JR. Molecular biology (squamous cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:353–360.
Cobb MW. Skin cancer in the immunosuppressed host. In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:51–60.
McGregor JM, Hawk JL. Genetic syndromes predisposing to skin cancer development. In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:158–168.
Boeta-Angeles L, Bennett RG. Features associated with recurrence (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:646–656.
Haas AF. Features associated with metastasis (squamous cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:500–505.
Swanson NA, Johnson TM. Management of basal and squamous cell carcinoma. In: Cummings C, ed. Otolaryngology Head and Neck Surgery. New York: Mosby Yearbook; 1998:486–501.
Rowe DE, Carroll RJ, Day CL Jr. 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;26:976–990.
Silverman MK, Kopf AW, Grin CM et al.. Recurrence rates of treated basal cell carcinomas. Part 1: overview. J Dermatol Surg Oncol 1991;17:713–718.
Silverman MK, Kopf AW, Grin CM et al.. Recurrence rates of treated basal cell carcinomas. Part 2: curettage-electrodesiccation. J Dermatol Surg Oncol 1991;17:720–726.
Medicare Part B Newsletter No. 023. February 6, 1998.
Rowe DE, Carroll RJ, Day CL Jr. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. J Dermatol Surg Oncol 1989;15:315–328.
Gupta AK, Cardella CJ, Haberman HF. Cutaneous malignant neoplasms in patients with renal transplants. Arch Dermatol 1986;122:1288–1293.
Stern RS, Lange R. Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment. J Invest Dermatol 1988;91:120–124.
Stern RS, Liebman EJ, Vakeva L. Oral psoralen and ultraviolet-A light (PUVA) treatment of psoriasis and persistent risk of nonmelanoma skin cancer. PUVA follow-up study. J Natl Cancer Inst 1998;90:1278–1284.
Brodland DG. Features associated with metastasis (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:657–663.
Edwards MJ, Hirsch RM, Broadwater JR et al.. Squamous cell carcinoma arising in previously burned or irradiated skin. Arch Surg 1989;124:115–117.
Galloway TJ, Morris CG, Mancuso AA et al.. Impact of radiographic findings on prognosis for skin carcinoma with clinical perineural invasion. Cancer 2005;103:1254–1257.
Salasche SJ. Features associated with recurrence (squamous cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:494–499.
Leffell DJ, Headington JT, Wong DS, Swanson NA. Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol 1991;127:1663–1667.
Dinehart SM, Dodge R, Stanley WE et al.. Basal cell carcinoma treated with Mohs surgery. A comparison of 54 younger patients with 1050 older patients. J Dermatol Surg Oncol 1992;18:560–566.
Milroy CJ, Horlock N, Wilson GD, Sanders R. Aggressive basal cell carcinoma in young patients: fact or fiction? Br J Plast Surg 2000;53:393–396.
Roudier-Pujol C, Auperin A, Nguyen T et al.. Basal cell carcinoma in young adults: not more aggressive than in older patients. Dermatology 1999;199:119–123.
Lowe L. Histology (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:633–645.
Maloney ME, Miller SJ. Aggressive vs nonaggressive subtypes (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:609–613.
Costantino D, Lowe L, Brown DL. Basosquamous carcinomaan under-recognized, high-risk cutaneous neoplasm: case study and review of the literature. J Plast Reconstr Aesthet Surg 2006;59:424–428.
Martin RC II, Edwards MJ, Cawte TG et al.. Basosquamous carcinoma: analysis of prognostic factors influencing recurrence. Cancer 2000;88:1365–1369.
Schuller DE, Berg JW, Sherman G, Krause CJ. Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis. Otolaryngol Head Neck Surg 1979;87:420–427.
Fitzpatrick PJ, Harwood AA. Acute epithelioma—an aggressive squamous cell carcinoma of the skin. Am J Clin Oncol 1985;8:468–471.
Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 1992;26:467–484.
Brantsch KD, Meisner C, Schonfisch B et al.. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008;9:713–720.
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;79:915–919.
Goepfert H, Dichtel WJ, Medina JE et al.. Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984;148:542–547.
Chen K, Craig JC, Shumack S. Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol 2005;152:518–523.
Kovach BT, Murphy G, Otley CC et al.. Oral retinoids for chemoprevention of skin cancers in organ transplant recipients: results of a survey. Transplant Proc 2006;38:1366–1368.
Otley CC, Stasko T, Tope WD, Lebwohl M. Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg 2006;32:562–568.
Levi F, La Vecchia C, Te VC et al.. Incidence of invasive cancers following basal cell skin cancer. Am J Epidemiol 1998;147:722–726.
Marghoob AA, Slade J, Salopek TG et al.. Basal cell and squamous cell carcinomas are important risk factors for cutaneous malignant melanoma. Screening implications. Cancer 1995;75:707–714.
Bath-Hextall F, Bong J, Perkins W, Williams H. Interventions for basal cell carcinoma of the skin: systematic review. BMJ 2004;329:705.
Bath-Hextall FJ, Perkins W, Bong J, Williams HC. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2007;CD003412.
Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol 1992;27:241–248.
Pennington BE, Leffell DJ. Mohs micrographic surgery: established uses and emerging trends. Oncology (Williston Park) 2005;19:1165–1171.
Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 1989;15:424–431.
Freeman RG, Knox JM, Heaton CL. The treatment of skin cancer: a statistical study of 1,341 skin tumors comparing results obtained with irradiation, surgery, and curettage followed by electrodesiccation. Cancer 1964;17:535–538.
Mendenhall WM, Parsons JT, Mendenhall NP, Million RR. T2-T4 carcinoma of the skin of the head and neck treated with radical irradiation. Int J Radiat Oncol Biol Phys 1987;13:975–981.
Petrovich Z, Kuisk H, Langholz B et al.. Treatment results and patterns of failure in 646 patients with carcinoma of the eyelids, pinna, and nose. Am J Surg 1987;154:447–450.
Robins P, Rodriguez-Sains R, Rabinovitz H, Rigel D. Mohs surgery for periocular basal cell carcinomas. J Dermatol Surg Oncol 1985;11:1203–1207.
Avril MF, Auperin A, Margulis A et al.. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 1997;76:100–106.
Barrett TL, Greenway HT Jr, Massullo V, Carlson C. Treatment of basal cell carcinoma and squamous cell carcinoma with perineural invasion. Adv Dermatol 1993;8:277–304; discussion 305.
Chao CK, Gerber RM, Perez CA. Reirradiation of recurrent skin cancer of the face. A successful salvage modality. Cancer 1995;75:2351–2355.
Childers BJ, Goldwyn RM, Ramos D et al.. Long-term results of irradiation for basal cell carcinoma of the skin of the nose. Plast Reconstr Surg 1994;93:1169–1173.
Fitzpatrick PJ. Organ and functional preservation in the management of cancers of the eye and eyelid. Cancer Invest 1995;13:66–74.
Lovett RD, Perez CA, Shapiro SJ, Garcia DM. External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 1990;19:235–242.
Mazeron JJ, Chassagne D, Crook J et al.. Radiation therapy of carcinomas of the skin of nose and nasal vestibule: a report of 1676 cases by the Groupe Europeen de Curietherapie. Radiother Oncol 1988;13:165–173.
Petrovich Z, Kuisk H, Langholz B et al.. Treatment of carcinoma of the skin with bone and/or cartilage involvement. Am J Clin Oncol 1988;11:110–113.
Petrovich Z, Parker RG, Luxton G et al.. Carcinoma of the lip and selected sites of head and neck skin. A clinical study of 896 patients. Radiother Oncol 1987;8:11–17.
Silverman MK, Kopf AW, Bart RS et al.. Recurrence rates of treated basal cell carcinomas. Part 3: surgical excision. J Dermatol Surg Oncol 1992;18:471–476.
Silverman MK, Kopf AW, Gladstein AH et al.. Recurrence rates of treated basal cell carcinomas. Part 4: x-ray therapy. J Dermatol Surg Oncol 1992;18:549–554.
Smith SP, Foley EH, Grande DJ. Use of Mohs micrographic surgery to establish quantitative proof of heightened tumor spread in basal cell carcinoma recurrent following radiotherapy. J Dermatol Surg Oncol 1990;16:1012–1016.
Smith SP, Grande DJ. Basal cell carcinoma recurring after radiotherapy: a unique, difficult treatment subclass of recurrent basal cell carcinoma. J Dermatol Surg Oncol 1991;17:26–30.
Wilder RB, Shimm DS, Kittelson JM et al.. Recurrent basal cell carcinoma treated with radiation therapy. Arch Dermatol 1991;127:1668–1672.
Lukas VanderSpek LA, Pond GR, Wells W, Tsang RW. Radiation therapy for Bowen's disease of the skin. Int J Radiat Oncol Biol Phys 2005;63:505–510.
Braathen LR, Szeimies RM, Basset-Seguin N et al.. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol 2007;56:125–143.
Marmur ES, Schmults CD, Goldberg DJ. A review of laser and photodynamic therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg 2004;30:264–271.
Zeitouni N, Oseroff A, Shieh S. Photodynamic therapy for nonmelanoma skin cancers. Current review and update. Mol Immunol 2003;39:1133–1136.
Rhodes LE, de Rie MA, Leifsdottir R et al.. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol 2007;143:1131–1136.
Patel GK, Goodwin R, Chawla M et al.. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2006;54:1025–1032.
Gupta AK, Davey V, McPhail H. Evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: critical review and meta-analysis of efficacy studies. J Cutan Med Surg 2005;9:209–214.
Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol 2006;126:1251–1255.
Tanghetti E, Werschler P. Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp. J Drugs Dermatol 2007;6:144–147.
Morton C, Horn M, Leman J et al.. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or fluorouracil for treatment of squamous cell carcinoma in situ: results of a multicenter randomized trial. Arch Dermatol 2006;142:729–735.
Pariser DM, Lowe NJ, Stewart DM et al.. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial. J Am Acad Dermatol 2003;48:227–232.
Mullen JT, Feng L, Xing Y et al.. Invasive squamous cell carcinoma of the skin: defining a high-risk group. Ann Surg Oncol 2006;13:902–909.
Ch'ng S, Maitra A, Allison RS et al.. Parotid and cervical nodal status predict prognosis for patients with head and neck metastatic cutaneous squamous cell carcinoma. J Surg Oncol 2008;98:101–105.
Palme CE, O'Brien CJ, Veness MJ et al.. Extent of parotid disease influences outcome in patients with metastatic cutaneous squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2003;129:750–753.
Audet N, Palme CE, Gullane PJ et al.. Cutaneous metastatic squamous cell carcinoma to the parotid gland: analysis and outcome. Head Neck 2004;26:727–732.
Han A, Ratner D. What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion? Cancer 2007;109:1053–1059.
Veness MJ, Palme CE, Smith M et al.. Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope 2003;113:1827–1833.
Veness MJ, Morgan GJ, Palme CE, Gebski V. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope 2005;115:870–875.
Laramore GE, Scott CB, al-Sarraf M et al.. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup study 0034. Int J Radiat Oncol Biol Phys 1992;23:705–713.
Bernier J, Domenge C, Ozsahin M et al.. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945–1952.
Cooper JS, Pajak TF, Forastiere AA et al.. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937–1944.
Bernier J, Cooper JS, Pajak TF et al.. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005;27:843–850.
Robinson JK. Follow-up and prevention (basal cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998:695–698.
Shin DM, Maloney ME, Lippman SM. Follow-up and prevention (squamous cell carcinoma). In: Miller SJ, Maloney ME, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Management. Malden: Blackwell Science; 1998.
Von Hoff DD, LoRusso PM, Rudin CM et al.. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164–1172.
Woods RL, Stewart JF. Metastatic basal cell carcinoma: report of a case responding to chemotherapy. Postgrad Med J 1980;56:272–273.
Wieman TJ, Shively EH, Woodcock TM. Responsiveness of metastatic basal-cell carcinoma to chemotherapy. A case report. Cancer 1983;52:1583–1585.
Guthrie TH Jr, Porubsky ES, Luxenberg MN et al.. Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy. J Clin Oncol 1990;8:342–346.
Carneiro BA, Watkin WG, Mehta UK, Brockstein BE. Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. Cancer Invest 2006;24:396–400.
Jefford M, Kiffer JD, Somers G et al.. Metastatic basal cell carcinoma: rapid symptomatic response to cisplatin and paclitaxel. ANZ J Surg 2004;74:704–705.
Shin DM, Glisson BS, Khuri FR et al.. Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer. J Clin Oncol 2002;20:364–370.
Brewster AM, Lee JJ, Clayman GL et al.. Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol 2007;25:1974–1978.
Martinez JC, Otley CC, Okuno SH et al.. Chemotherapy in the management of advanced cutaneous squamous cell carcinoma in organ transplant recipients: theoretical and practical considerations. Dermatol Surg 2004;30:679–686.