eMedicine Specialties > Dermatology > Malignant Neoplasms

Basal Cell Carcinoma: Treatment & Medication

Author: Michael L Ramsey, MD, Director, Mohs Surgery Fellowship, Co-Director, Procedural Dermatology Fellowship, Department of Dermatology, Geisinger Medical Center
Coauthor(s): Lindsay Dane Sewell, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Contributor Information and Disclosures

Updated: Sep 11, 2009

Treatment

Medical Care

Local therapy with chemotherapeutic and immune-modulating agents is useful in some cases of basal cell carcinoma (BCC). In particular, small and superficial BCC may respond to these compounds. In addition, they may be used for prophylaxis or maintenance in patients who are prone to having many BCCs, such as those with basal cell nevus syndrome. See Medication. Also see the clinical guideline summary from the British Association of Dermatologists, Guidelines for the management of basal cell carcinoma.¹²

Surgical Care

The goal of surgical treatment of basal cell carcinoma (BCC) is to destroy or remove the tumor so that no malignant tissue is allowed to proliferate further. Factors to consider when choosing therapy include the histologic subtype of BCC, the location and size of tumors, the age of the patient, the patient's ability to tolerate surgery, and the expense. Recurrent tumors are generally more aggressive than primary lesions, and subclinical extension also tends to be increased. Tumors that are aggressive and those occurring near vital or cosmetically sensitive structures are best treated with methods that allow for an examination of the tissue margins.
The most common surgical methods are curettage, excision with margin examination, Mohs micrographic surgery, and radiotherapy. Additionally, cryotherapy is sometimes used to treat these tumors (see Media File 9).

• Curettage (usually with electrodesiccation) for basal cell carcinoma¹³
  • A looped blade (curette) is used to vigorously scrape tumor away from adjacent normal skin. One may start with a larger curette to debulk the tumor and then follow with a smaller curette to better remove smaller fragments of tumor from surrounding stroma. This technique works best in nodular or superficial BCC because these tumors tend to be friable and do not tend to be embedded in fibrous stroma. The instrument is applied firmly and used in multiple directions over the tumor and immediately adjacent skin. Curetting is most often followed by electrodesiccation, and the entire process may be repeated 1-2 more times. If electrodesiccation is not performed, vigorous and firm scraping in several directions is especially important. Many recurrences after curettage are believed to be due to insufficient aggressiveness on the part of the surgeon. The overall cure rate exceeds 90% for low-risk BCCs. The method is quick, simple, and less expensive than most other methods.
  • Curettage is a blind technique in which the specimen cannot be examined for margin control. This lack of microscopic margin control limits the usefulness of curettage in high-risk areas, such as the face and ears. Furthermore, the aggressive subtypes of BCC, such as morpheaform, infiltrating, micronodular, and recurrent tumors, are usually not friable and therefore unlikely to be removed by using the curette. The success of this treatment, even in nonaggressive tumors in low-risk sites, highly depends on the operator's experience and technique. Finally, healing by secondary intention (granulation) often leads to atrophic, white scars that may not be satisfactory in aesthetically important areas.
• Surgical excision for basal cell carcinoma¹⁴
  • One may surgically excise the clinically apparent tumor and a margin of clinically normal–appearing skin. This method can usually be performed in an ambulatory setting and provides the pathologist with a specimen to examine the tissue margins. Healing time is generally shorter with sutured closure than with granulation, and cosmesis compares favorably with that of curettage.
  • Surgical excision is more time-consuming and costly than curettage. In addition, this method requires sacrifice of normal tissue to obtain acceptable cure rates. Margins of at least 4 mm are needed, even with the least aggressive BCCs, to achieve 95% cure rates. If standard bread-loaf tissue sectioning is used, areas of margin involvement may be missed under microscopy because only a small sampling of the specimen is evaluated.
• Mohs micrographic surgery for basal cell carcinoma^15,16
  • Mohs surgery involves removal of the clinically apparent tumor and a thin rim of normal-appearing skin around the defect. This saucer-shaped tissue specimen represents tissue adjacent to the tumor or the margin surrounding the tumor. This margin specimen is sectioned and marked so that the entirety of the undersurface and outer edges of the tumor are examined microscopically to minimize sampling error. Use of the frozen-section technique allows for an examination of tissue while the patient is in the office. Tissue is mapped microscopically so if any foci of tumor persist, further excision can be directed to only those areas to spare the normal tissue.
  • With the Mohs technique, almost 100% of the tissue margins are examined, compared with standard vertical (bread-loaf) sectioning, in which less than 1% of the outer margins are examined. Because relatively thin layers are taken only in areas of proven tumor, this technique is tissue sparing. Excision and repair can usually be performed on the same day. Of most importance, Mohs micrographic surgical excision has the best long-term cure rates of any treatment modality for BCC. Cure rates for primary BCC are 98-99% with Mohs excision and 94-96% for recurrent BCC.
  • Massive, invasive BCC tumors may sometimes be treated with Mohs surgery to clear peripheral margins with deeper aspects treated surgically by other disciplines.¹⁷
  • Chief disadvantages of Mohs surgery are its increased expense and time requirement compared with curettage. Mohs excision compares favorably with standard surgical excision when one factors in the savings of treating fewer recurrences with this technique.
• Radiation therapy for basal cell carcinoma¹⁸
  • Radiation therapy is effective as primary treatment for a variety of BCCs. For most BCCs, cure rates approach 90%. It is especially useful for patients who cannot easily tolerate surgery, such as elderly or debilitated individuals. Irradiation can also be a useful adjunct when patients have aggressive tumors that were treated surgically or when surgery has failed to clear the margins of the tumor. Radiation is also an excellent option in patients who refuse surgery because of the size of a lesion or its proximity to vital structures.
  • Initial cosmetic results tend to be good, and this therapy can be less disfiguring than surgical excision. However, long-term results after several years can be deforming. Another disadvantage of this technique is that surgical margins cannot be examined. Tumors recurring in previously radiated sites tend to be aggressive and difficult to treat and reconstruct. Radiation therapy remains an important, feasible option in selected patients with BCC.
• Cryotherapy for basal cell carcinoma
  • Cryotherapy is also an effective treatment for most nonaggressive BCCs, with cure rates near 90%. However, successful treatment is highly dependent on the experience of the operator. Optimal cure rates are obtained when the depth, duration, and temperature of treatment are measured with special instrumentation, such as cryoprobes.
  • Patients must be willing to endure the immediate posttreatment swelling, resultant necrosis of treated areas, and unpredictable scarring that can occur with this approach.
  • This method is not commonly used for the treatment of BCC, except by a few experienced cryosurgeons.

Medication

Imiquimod 5% cream¹⁹ has been used successfully to treat superficial basal cell carcinomas (BCCs).^19,20,21,22 Although its exact mode of action in treating BCC is not known, a few suggested mechanisms follow. Lymphocytes, dendritic cells, and macrophages may be recruited into the area of imiquimod application. These cells may be activated via toll-like receptors 7 and 8 (both of which recognize imiquimod as a ligand) to release cytokines, particularly tumor necrosis factor-alpha, interferon-alpha, and interleukin 6. Antitumor effects, such as apoptosis, may then proceed, thereby inducing tumor regression.²³ Induction of tumor suppressor function via the Notch signaling pathway in superficial BCCs has also been suggested as a mechanism of imiquimod.^21,24  
 
The current recommended dosing frequency for the treatment of superficial BCC is 5 times per week for 6 weeks, but the frequency and duration should be tailored to the individual patient's response and ability to tolerate the medication. Many application schedules have been used, ranging from 3 times per week to twice daily 7 d/wk. The duration of treatment varies from 6-16 weeks. Superficial BCC cure rates of 70-100% should be expected after a 6-week course of 5-times-per-week application, as shown in studies. Topical imiquimod has also been used to treat small, nodular BCCs in low-risk locations, but cure rates have been lower than those with superficial BCCs.

Although successful use of imiquimod in immunosuppressed populations (eg, transplantation patients) without systemic complications has been documented, it has not been widely studied, nor have safety and efficacy been established. Imiquimod should be used cautiously in patients with autoimmune disease. Additionally, its high cost may prohibit its use in some patients.
 
Topical 5-fluorouracil 5% cream²⁵ is sometimes used to treat small, superficial BCCs. It is a fluorinated pyrimidine that "blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell."
 
In properly selected (eg, thin) tumors, cure rates of approximately 80% have been obtained. It is generally applied twice daily and must be used for at least 6 weeks for the treatment of superficial BCC. Percutaneous absorption of 5-fluorouracil is its major limiting factor; it penetrates only 1 mm into the skin. New vehicles that may enhance absorption of 5-fluorouracil are being investigated.

One advantage of 5-fluorouracil use is that it can act on BCCs that are not large enough to be seen with the unaided eye. Therefore, it may be used in patients with basal cell nevus syndrome or in individuals prone to develop many BCCs to preemptively treat subclinical tumors. Patients with BCCs that are treated with 5-fluorouracil should be monitored carefully because not all tumors completely respond. Cosmetic results tend to range from good to excellent with the use of 5-fluorouracil. Although it is not inexpensive, it does cost less than imiquimod.

Interferon alfa-2b has shown some success in treating small (<1 cm), nodular, and superficial BCCs. It is administered intralesionally, 3 times per week for 3 weeks. The recommended dose is 1.5 million units per injection (total of 13.5 million U). In appropriate BCC tumors, cures rates of up to 80% have been obtained. Interferon has not become a mainstay in BCC treatment because of its cost, the inconvenience of multiple visits, the discomfort of administration, and its adverse effects. Flulike symptoms, which are dose related, are common with the doses administered to treat BCCs. Cardiovascular, myelodepressive, and neurologic adverse effects are less common with this treatment than with others. Because interferon is an immune stimulant, it should not be used to treat BCC in transplant recipients or in individuals with autoimmune diseases.

Photodynamic therapy (PDT) for BCCs has been used for more than 20 years.²⁶ PDT is the process of using specific wavelengths of light to photoexcite porphyrins that have been applied to neoplastic and preneoplastic cells. This increased energy is rapidly absorbed by adjacent tissue oxygen, causing the formation of singlet oxygen radicals. These radicals rapidly react with adjacent tissue and destroy it. 5-Aminolevulinic acid (ALA-PDT) is the only US Food and Drug Administration approved photoreactive molecule for PDT in the United States, and it is only approved for actinic keratoses. It is photoactivated with blue light for 1000 seconds after 1 hour of incubation.

Although its use is off label, PDT has been used for treatment and prevention of BCCs, including patients with immunosuppression and nevoid BCC syndrome. Shallow tumors, such as superficial BCCs, respond most consistently. Surgical excision has been shown to be significantly more effective than ALA-PDT in the treatment of nodular BCC.²⁷ The strongest support for PDT as a modality for BCCs comes with data on thin lesions treated with methylaminolevulinate (used outside the United States), but at least one long-term follow-up trial has also shown surgical excision to be superior.^28,29 Various protocols have been followed to achieve varying levels of success—increasing the incubation time, increasing occlusion time, and using longer and/or deeper-penetrating wavelengths of light (eg, red light or pulse-dye laser). Many patients continue to prefer PDT because of its short healing time, excellent cosmesis, and relative affordability.

Also see the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee’s clinical guidelines summary, Guidelines for topical photodynamic therapy: update.³⁰

Antineoplastic agents

Topical or intralesional antineoplastic agents may be administered depending on the type, location, and stage of the basal cell carcinoma (BCC).

5-Fluorouracil (Efudex, Carac, Fluoroplex)

Used topically to manage superficial BCC (not on head or neck). Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid and inhibiting thymidylate synthetase and, subsequently, cell proliferation.

Imiquimod (Aldara)

Precise mechanism for superficial BCC unknown. May increase tumor infiltration of lymphocytes, dendritic cells, and macrophages. Indicated for biopsy-confirmed primary superficial BCC (not on head or neck) in adults with normal immune systems. Tumors must not be >2 cm in diameter on certain areas of body. Indicated only when surgical methods not appropriate.

Interferon alfa-2b (Intron A)

Protein product manufactured with recombinant DNA technology. Mechanism of antitumor activity not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may be important. Investigational use for nodular BCC. Used in a randomized, placebo-controlled multicenter study (172 subjects). Intralesional injections of 1.5 million U administered 3 times/wk for 3 wk yielded 86% complete-response rate; 29% for placebo. Study included nodular BCCs; similar study did not show efficacy for morpheaform or aggressive BCCs.

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