Basal-cell Carcinoma

Basal-cell carcinoma (BCC), a skin cancer, is the most common cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant.

Statistically, in the United States approximately 3 out of 10 Caucasians may develop a basal-cell cancer within their lifetime. In 80 percent of all cases, basal-cell cancers are found on the head and neck. There appears to be an increase in the incidence of basal-cell cancer of the trunk (torso) in recent years.

Treatment

The following methods are employed in the treatment of basal-cell carcinoma (BCC):

Standard surgical excision

This can be with either frozen section histology, or paraffin-embedded fixed-tissue pathology. It is the preferred method for removal of most BCCs. A dermatoscope can help an experienced surgeon accurately identify the visible tumour that the naked eye can not see.

The cure rate for this method, whether performed by an otolaryngologist-head & neck surgeon, plastic surgeon, or dermatologist is totally dependent on the surgical margin. The narrower the free surgical margin (skin removed that is free of visible tumor) the higher the recurrence rate. If a 4 mm free surgical margin is obtained around a small tumor (less than 6mm), or a wider 6 mm free surgical margin is obtained around a larger tumor (greater than 6mm), the cure rate is very high - 95% or better. However, for cosmetic reasons, many doctors take only very small surgical margins 1–2 mm, especially when operating on the face. In such a case, a pathology report indicating the margins are free of residual tumour is often inaccurate, and a recurrence rates are much higher (up to 38%).

A weakness with standard surgical excision is the high recurrence rate of basal-cell cancers of the face, especially around eyelids, nose, and facial structures. A diagram on page 38 of the National Comprehensive Cancer Network publication demonstrate the area of high risk of recurrence as most the face with the exception of the central cheek and upper forehead. On the face, or on recurrent basal-cell cancer after previous surgery, special surgical margin controlled processing (CCPDMA - complete circumferential peripheral and deep margin assessment using frozen section histology (Mohs surgery is one of the methods) is required.

With surgical margin controlled frozen section histology, a surgeon can achieve a high cure rate and low recurrence rate on the same day of the excision. However, most standard excisions done in a plastic surgeon or dermatologist's office are sent to an outside laboratory for standard bread loafing method of processing. With this method, it is likely that less than 5% of the surgical margin is examined, as each slice of tissue is only 6 micrometres thick, about 3 to 4 serial slices are obtained per section, and only about 3 to 4 sections are obtained per specimen.

When in doubt, a patient should demand that either Mohs surgery or frozen section histology with either margin control (ccpdma) or thin serial bread-loafing is utilized when dealing with a tumour on the face. The pathologist processing the frozen section specimen should cut multiple sections through the block to minimize the false negative error rate. Or one should simply process the tissue utilizing a method approximating the Mohs method (described in most basic histopathology text books or described in this reference) during frozen section processing. Unfortunately, these methods are difficult when applied to frozen sections; and is very tedious to process. When not utilizing frozen section, the surgeon might have to wait a week or more, before informing the patient if more tumour is left, or if the surgical margin is too narrow. And a second surgery must be performed to remove the residual or potential residual tumour once the surgeon informs the patient of the positive or narrow surgical margin on the surgical pathology report.

Mohs surgery

Mohs surgery (or Mohs micrographic surgery) is an outpatient procedures in which the tumor is surgically excised and then immediately examined under a microscope. It is a form of pathology processing called CCPDMA. The base and edges are microscopically examined to verify sufficient margins before the surgical repair of the site. If the margins are insufficient, more is removed from the patient until the margins are sufficient. It is also used for squamous-cell carcinoma; however, the cure rate is not as high as Mohs surgery for basal-cell carcinoma.

Chemotherapy

Some superficial cancers respond to local therapy with 5-fluorouracil, a chemotherapy agent. Topical treatment with 5% Imiquimod cream, with five applications per week for six weeks has a reported 70-90% success rate at reducing, even removing, the BCC [basal-cell carcinoma]. Both Imiquimod and 5-fluorouracil have received FDA approval for the treatment of superficial basal-cell carcinoma. Off label use of imiquimod on invasive basal-cell carcinoma has been reported. Imiquimod may be used prior to surgery in order to reduce the size of the carcinoma. One can expect a great deal of inflammation with this treatment. Chemotherapy often follows Mohs surgery to eliminate the residual superficial basal-cell carcinoma after the invasive portion is removed. Some advocate the use of imiquimod prior to Mohs surgery to remove the superficial component of the cancer[35] Removing the residual superficial tumor with surgery alone can result in large and difficult to repair surgical defects. One often waits a month or more after surgery before starting the Imiquimod or 5-fluorouracil to make sure the surgical wound has adequately healed. Some individuals advocate the use of curettage (see EDC below) first, then followed by chemotherapy. These experimental procedures are not standard care.

Immunotherapy

Immunotherapy research suggests that treatment using Euphorbia peplus, a common garden weed, may be effective. Australian biopharmaceutical company Peplin is developing this as topical treatment for BCC. Imiquimod or Aldara is an immunotherapy but is listed here under chemotherapy.

Radiation

Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (internal radiotherapy). Although radiotherapy is generally used in older patients who are not candidates for surgery, it is also used in cases where surgical excision will be disfiguring or difficult to reconstruct (especially on the tip of the nose, and the nostril rims). Radiation treatment often takes as few as 5 visits to as many as 25 visits for radiation therapy. Usually, the more visits scheduled for therapy, the less complication or damage is done to the normal tissue supporting the tumor. Radiotherapy can also be useful if surgical excision has been done incompletely or if the pathology report following surgery suggests a high risk of recurrence, for example if nerve involvement has been demonstrated. Cure rate can be as high as 95% for small tumor, or as low as 80% for large tumors. Usually, recurrent tumors after radiation are treated with surgery, and not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation. Radiation therapy may be contraindicated for treatment of nevoid basal cell carcinoma syndrome.

Photodynamic therapy

Photodynamic therapy is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types.

Cryosurgery

Cryosurgery is an old modality for the treatment of many skin cancers. When accurately utilized with a temperature probe and cryotherapy instruments, it can result in very good cure rate. Disadvantages include lack of margin control, tissue necrosis, over or under treatment of the tumor, and long recovery time. Overall, there are sufficient data to consider cryosurgery as a reasonable treatment for BCC. There are no good studies, however, comparing cryosurgery with other modalities, particularly with Mohs surgery, excision, or electrodesiccation and curettage so that no conclusion can be made whether cryosurgery is as efficacious as other methods. Also, there is no evidence on whether curetting the lesions before cryosurgery affects the efficacy of treatment. Several textbooks are published on the therapy, and a few physicians still apply the treatment to selected patients.

Electrodesiccation and curettage

Electrodesiccation (EDC) is accomplished by using a round knife, or curette, to scrape away the soft cancer. The skin is then burned with an electric current. This further softens the skin, allowing for the knife to cut more deeply with the next layer of curettage. The cycle is repeated, with a safety margin of curettage of normal skin around the visible tumor. This cycle is repeated 3 to 5 times, and the free skin margin treated is usually 4 to 6 mm. Cure rate is very much user-dependent and depends also on the size and type of tumor. Infiltrative or morpheaform BCCs can be difficult to eradicate with EDC. Generally, this method is used on cosmetically unimportant areas like the trunk (torso). Some physicians believe that it is acceptable to utilize EDC on the face of elderly patients over the age of 70. However, with increasing life expectancy, such an objective criterion cannot be supported. The cure rate can be low or high, depending on the aggressiveness of the EDC and the free margin treated. Some advocate curettage alone without electrodesiccation, and with the same cure rate.

Treating surgeons will recommend one of these modalities as appropriate treatment depending on the tumour size, location, patient age, and other variables.

Vismodegib

Approved in 2012, vismodegib (trade name Erivedge) is a new drug indicated for the treatment of an advanced form of basal cell carcinoma.