Based on the National Comprehensive Cancer Network (NCCN) guidelines, the main goal of basal cell carcinoma (basalioma) treatment is eliminating cancer with maximum preservation of function and cosmetics. Therefore, the decision to carry out therapy must be based on the desires and individual risk factors of each patient.

Basal Cell Carcinoma treatment
Advanced Basal Cell Carcinoma 

A. Surgery

The target of surgical therapy for basal cell carcinoma is removing cancer with the best cosmetic results. The effectiveness of this modality depends on the doctor's abilities to perform the surgery.

The NCCN recommends that low-risk basalioma in hairless areas, treated with electrodesiccation or curettage. Excision is needed if cancer affects fat tissue. Standard excision is an alternative if the lesion can be excised with a 4 mm clinical boundary with the second intention of healing, linear repair, or skin grafting. Boundary incisions must be evaluated after surgery.

For high-risk basal cell carcinomas, excision is recommended by evaluating postoperative incision limits or Mohs micrographic surgery. Some studies suggest that dermato-oncology surgery is associated with an increased risk of infection, especially in diabetic patients and the location of surgery is the lower extremities.

One study reported that a cure rate for 5 years of ≥95% was possible with the use of therapeutic modalities of curettage and cautery or cryosurgery if performed on a small, well-defined, low-risk basalioma in the form of primary lesions located in the neck, trunk, hands, and foot, without aggressive histopathological features.

Excision and Mohs micrographic surgery have a cure rate of 5 years above 99% for primary lesions of any size in the neck, trunk, hands, and feet.

Excision on the face has a worse prognosis by the increasing size of the lesion. In lesions measuring <6 mm, the cure rate for 5 years is 97%.topical therapy

B. Topical Therapy

Some topical agents are applied to superficial and non-recurrent basal cell carcinoma. Based on the NCCN, low-risk patients with superficial basalioma, who cannot undergo surgery or radiotherapy, are advised to undergo topical therapy even if the degree of curative is not too high. This therapeutic modality is also given to patients with multiple high-risk primary tumors.

5-fluorouracil 5% topically
5-fluorouracil 5% cream can be applied to superficial basalioma, which is small and in low-risk areas. 5-fluorouracil works by inhibiting DNA synthesis by inhibiting the methylation of deoxyuridylic acid and thymidylate synthase so that it implies a decrease in cell proliferation.

By appropriate cancer selection, a curative degree of 80% can be achieved. This cream is applied twice a day and applied for a minimum of 6 weeks for the treatment of superficial basalioma. Because this therapy can work in visible basalioma, it can be used for subclinical cancer therapy in patients with basal cell nevus syndrome.

This therapy cannot be given to other types of basalioma because the degree of penetration is not deep enough to reach the dermis to eradicate the entire cancer cell. Irritation and crusting are often found. The degree of recurrence of this therapy is also very high.

The FDA has approved imiquimod 5% cream for superficial basalioma treatment in areas outside the face. Therapy is generally given 3-7 times each week with doses titrated from 1-2 times per day to minimize skin irritation. Generally, therapy is given for 12 weeks.

Tazarotene is an acetylenic retinoid that is selective towards receptors that can be used for the management of low-risk and small-sized basaliomas. Tazarotene is known to cause basalioma regression by increasing apoptosis and decreasing cell proliferation in skin cancer cells. Aside from being still off label, the drawback of this therapy is that it requires a period of therapy for 5-8 months.
Basaliomas are generally radiosensitive, so radiotherapy is recommended in advanced basalioma and for patients who cannot undergo surgery. Postoperative radiation can be used as an adjuvant in patients with aggressive cancer who undergo surgery or non-cancerous surgical incision boundaries.
The use of this modality in advanced stage basalioma can achieve complete remission in 70% of patients. Radiotherapy also gives satisfactory results in cosmetics, generally accompanied by a little hypopigmentation or telangiectasia at the radiation site.

C. Radiotherapy

Radiotherapy can be a therapeutic choice in patients with recurrent cancer. Radiotherapy can also be used in primary lesions that require complicated oculoplastic surgery and reduce the need for skin grafts if surgery produces extensive defects.

Radiotherapy is recommended for older patients but is contraindicated in young patients because of the high risk of causing radiodermatitis and scarring. Other contraindications include lesions on the body and extremities, connective tissue disease, the genetic predisposition that is susceptible to skin cancer, and delayed cancer recurrence (especially in patients who have had previous radiotherapy).

Other disadvantages include:
A. Need for repeat visits, 
B. Cannot evaluate the incision boundaries, 
C. Recurrence will produce more aggressive cancers, 
D. Have a risk of radiation damage, 
E. And less effective in cancers outside the facial area.

At present, the type of radiotherapy recommended is intensity-modulated radiotherapy (IMRT).

D. Photodynamic therapy

Photodynamic therapy (PDT) works through the use of light with specific wavelengths to photograph the excitation of porphyrins applied to neoplastic and preneoplastic cells. This increase in energy is rapidly absorbed by the tissue oxygen concerned to produce free radicals. These free radicals directly react to the relevant tissue, and then tissue destruction occurs. 5-aminolevulinic acid (ala) is the only one approved by the FDA as a photoreactive molecule for PDT in the US and only for actinic keratosis. Ala is photoactivated by blue light for 1000 seconds after 1 hour of incubation.

PDT is given orally, parenterally or topically, and then is localized to the cancer cell before it is activated through exposure to light (laser). Low efficacy causes PDT to be used for palliative therapy. Pdt can cause edema, erythema, vesicles, and ulceration, but it has good cosmetic results at the end of therapy. Based on the Calzavara-Pinton et al. Study, the PDT curative degree was 50% for superficial basalioma and 83% for nodular type basalioma.

E. Hedgehog path inhibitors

By the approval of the hedgehog pathway inhibitor (hh) by the FDA provides a new alternative in advanced basalioma patients who cannot be treated with surgery or radiotherapy.

Vismodegib is an FDA-approved drug for advanced stage basalioma. This drug works through inhibits SMO, which is a transmembrane protein associated with the transduction of hh signals. Based on the research used by the FDA to approve this drug, a partial response of 20% and a complete response of 20% in advanced basalioma were obtained, as well as a partial response of 30.3% in metastatic basalioma. The current recommended the vismodegib dose is 150 mg per day and is continued with consideration based on disease progression and toxicity.

Sonidegib is the second drug from the hh (hedgehog) pathway inhibitor, which is FDA-approved. Based on the bolt trial where the drug was administered to advanced-stage basalioma patients and basalioma who had metastasized, there was an overall response of 58% with a complete response of 5% and a partial response of 53%. The recommended sonidegib dosage given is 200 mg per day and continued with consideration based on disease progression and toxicity.

Recommendations in the selection of therapy

According to NCCN, the selection of basalioma therapy is based on the risk of basalioma recurrence.

Low risk
In low-risk basalioma, the treatments are curettage or electrodesiccation, standard excision with 4mm clinical boundary, or radiotherapy. If, after performing excision and getting an incision boundary is still positive for cancer, then do the Mohs micrographically controlled surgery, re-excision, or radiotherapy.

High risk
In high-risk basalioma, the treatment options are Mohs micrographically controlled surgery, excision with larger clinical boundaries, or radiotherapy. If, after making an excision and getting an incision boundary is still positive for cancer, then do the Mohs micrographically controlled surgery, re-excision, or radiotherapy.

If local recurrence occurs, the treatment is carried out again according to steps based on risk factors for basalioma recurrence. If recurrence occurs in lymph nodes or metastasis surgery, radiotherapy and consideration are given for hh inhibitors.

Source Picture:

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4. NCCN. Basal Cell Carcinoma. 2018.
5. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma. N Eng J Med, 2012. 366(23): 2171-9.
6. Lear JT, Migden MR, Lewis KD, Chang ALS, Guminskin A, Gutzmer R, et al. Long‐term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30‐month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol, 2018. 32(3): 372-81.