Basal cell carcinoma (BCC) is the most common human malignancy1 and by far the most prevalent form of skin cancer, accounting for over 80% of all cases.2 The typical BCC is a slow-growing tumor that is treatable by a variety of treatment modalities. Common in elderly, fair-skinned individuals,3 this disease occurs largely in sun-exposed areas of the body and is felt to be a result of chronic ultraviolet exposure.2
Treatment of BCC is fairly straightforward, with surgical, destructive and topical treatment options available.2 This results in a 5-year cure rate of over 90%.2 In certain cases, however, neglected, aggressive or recurrent BCC can progress to an advanced state.4 In extremely rare cases, BCC may metastasize to other anatomic locations, carrying a poor prognosis.4
The tumor characteristics that define a given cancer as being an advanced BCC can vary. When defining advanced BCC, there are certain features that render cancers challenging to treat. These include large size, extent and invasiveness of disease and difficult-to-treat locations (ie, ear canal or medial canthus).3
For example a 10-cm BCC on the back would be relatively straightforward to treat surgically, however, this tumor on the ear or invading deeply into the bones of the skull would pose significant therapeutic challenges. Likewise, a 1-cm tumor located on the medial canthus and extending on to both eyelids and the conjunctival surface of the eye is not a big tumor, but surgery may have to involve enucleation.4 No absolute definition exists of what qualifies a BCC as being advanced, and this is a decision made by the treating physicians.
Recurrent tumors can be more difficult to treat, as they are often multifocal in nature and cure rates of standard approaches, such as Mohs micrographic surgery, can be decreased. Patients with certain genetic conditions may exhibit a strong predisposition to the development of numerous aggressive BCCs that may develop to an advanced state. Among the most common of these conditions are basal cell nevus syndrome, xeroderma pigmentosum and oculocutaneous albinism.
Lastly, certain patient characteristics may also make standard surgical approaches challenging, limiting treatment options. This may include patients of advanced age, those with multiple comorbidities or of low functional status.5
Advanced BCC
When considering treatment options for advanced BCC, choices are limited. In these situations, less invasive options such as electrodesiccation, curettage, cryosurgery, photodynamic therapy or topical agents would not be effective.
When surgery is an option, this remains the gold standard for achieving the highest cure rate and should always be considered as first-line treatment. However, patients may not be ideal surgical candidates if they are unable to tolerate surgery or if surgery is so extensive that it would result in significant deformity or loss of function (eg, loss of an ear or an eye). See Figure 1 for potential treatment algorithm for advanced BCC.
Radiation therapy has been utilized for decades in a variety of tumors, and may be an option for certain advanced BCCs. Typically, radiation is delivered in fractions 5 days per week over several weeks. Radiation may be inappropriate in patients who cannot tolerate this dosing schedule, or who have failed prior radiation treatment or in tumors that have recurred following radiation.3 Radiation may be contraindicated for certain tumors because of ill-defined borders, those with tumors on the lower legs, feet, hands or genitalia and for patients with tumors arising in previously irradiated areas. Side effects, as with any treatment, may be intolerable for certain patients.5
Recently, a new class of medications known as hedgehog pathway inhibitors has been developed for the treatment of locally advanced and metastatic BCC. The first-in-class drug, vismodegib (Erivedge, Genentech) received FDA approval in January 2012.3 These oral agents are targeted to treat the underlying mutation found in close to 100% of all BCCs. As experience with their use increases, data on safety, efficacy and tolerability have begun to emerge.
Treatment Considerations
The decision for the best treatment option for patients with advanced BCC is complicated, and must incorporate both tumor and patient characteristics as well as prior treatment history. In several cases, more than one therapeutic modality may be appropriate and multidisciplinary input can be helpful.
For example, large, extensive tumors or those involving the vital structures of the face may be excised by Mohs surgeons under general anesthesia in conjunction with head and neck surgery or surgical oncology. Once clear margins are achieved, the patient can then undergo the appropriate reconstruction.
Often, tumors become advanced because of patient neglect and fear of medical care. In these patients, a discussion of extensive surgery or the associated high facility costs and recovery time involved may deter them from pursuing treatment for their advanced BCC. These patients may be better served with radiation or hedgehog inhibitors. Furthermore, nursing home patients with advanced degenerative disease and low functional status may also be good candidates for these medicines.
When developing a treatment plan, consider the characteristics of the BCC and the effects of therapy:
• Size
• Extent and invasiveness
• Difficult-to-treat location
• Recurrence
• Location
• Non-continuous growth
Surgery may be inappropriate if:
• Substantial deformity or functional loss may result (eg, loss of an ear)
• Patient cannot tolerate surgery
• Clear margins cannot be obtained
• Medical comorbidities prohibit surgery
Radiation may be inappropriate if:
• Radiation has failed previously
• A tumor has recurred following previous radiation
• If excessive radiation dose must be used
• If damage to underlying structures is a concern (eg, the eye)
Oral hedgehog inhibitors may be inappropriate if:
• Adverse effects are intolerable
• Patient’s tumor unsponsive to drug
• Tumor progresses despite treatment
In summary, management of advanced BCC should be individualized for each patient. One must consider functional and cosmetic outcome and tolerability of extensive surgical procedures.
When surgery is possible and clear margins can be achieved, this will give the patient the best chance for a long-term cure of their disease. In all situations, surgery should be considered first.
When surgery is not an option for factors related to the patient or to the cancer being treated, or if tumors have recurred following surgery, alternative treatment modalities such as radiation or oral hedgehog inhibitors may be considered.
Dr. Ibrahim is an assistant professor in dermatology, Division of Dermatologic Surgery, Wilmot Cancer Center at University of Rochester in Rochester, NY.
Disclosure: Dr. Ibrahim is a consultant and speaker for Genentech.
References
1. Caro I, Low J. The Role of the Hedgehog Signaling Pathway in the Development of Basal Cell Carcinoma and Opportunities for Treatment. Clinical Cancer Research. 2010;16:3335-3339.
2. Rubin AL, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262-2269.
3. Bader RS. Basal cell carcinoma treatment & management. Medscape. https://emedicine.medscape.com/article/276624-treatment#aw2aab6b6b4. Accessed January 21, 2014.
4. Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004;23(3-4):389-402.
5. Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol. 2007;4(8):462-469.
Basal cell carcinoma (BCC) is the most common human malignancy1 and by far the most prevalent form of skin cancer, accounting for over 80% of all cases.2 The typical BCC is a slow-growing tumor that is treatable by a variety of treatment modalities. Common in elderly, fair-skinned individuals,3 this disease occurs largely in sun-exposed areas of the body and is felt to be a result of chronic ultraviolet exposure.2
Treatment of BCC is fairly straightforward, with surgical, destructive and topical treatment options available.2 This results in a 5-year cure rate of over 90%.2 In certain cases, however, neglected, aggressive or recurrent BCC can progress to an advanced state.4 In extremely rare cases, BCC may metastasize to other anatomic locations, carrying a poor prognosis.4
The tumor characteristics that define a given cancer as being an advanced BCC can vary. When defining advanced BCC, there are certain features that render cancers challenging to treat. These include large size, extent and invasiveness of disease and difficult-to-treat locations (ie, ear canal or medial canthus).3
For example a 10-cm BCC on the back would be relatively straightforward to treat surgically, however, this tumor on the ear or invading deeply into the bones of the skull would pose significant therapeutic challenges. Likewise, a 1-cm tumor located on the medial canthus and extending on to both eyelids and the conjunctival surface of the eye is not a big tumor, but surgery may have to involve enucleation.4 No absolute definition exists of what qualifies a BCC as being advanced, and this is a decision made by the treating physicians.
Recurrent tumors can be more difficult to treat, as they are often multifocal in nature and cure rates of standard approaches, such as Mohs micrographic surgery, can be decreased. Patients with certain genetic conditions may exhibit a strong predisposition to the development of numerous aggressive BCCs that may develop to an advanced state. Among the most common of these conditions are basal cell nevus syndrome, xeroderma pigmentosum and oculocutaneous albinism.
Lastly, certain patient characteristics may also make standard surgical approaches challenging, limiting treatment options. This may include patients of advanced age, those with multiple comorbidities or of low functional status.5
Advanced BCC
When considering treatment options for advanced BCC, choices are limited. In these situations, less invasive options such as electrodesiccation, curettage, cryosurgery, photodynamic therapy or topical agents would not be effective.
When surgery is an option, this remains the gold standard for achieving the highest cure rate and should always be considered as first-line treatment. However, patients may not be ideal surgical candidates if they are unable to tolerate surgery or if surgery is so extensive that it would result in significant deformity or loss of function (eg, loss of an ear or an eye). See Figure 1 for potential treatment algorithm for advanced BCC.
Radiation therapy has been utilized for decades in a variety of tumors, and may be an option for certain advanced BCCs. Typically, radiation is delivered in fractions 5 days per week over several weeks. Radiation may be inappropriate in patients who cannot tolerate this dosing schedule, or who have failed prior radiation treatment or in tumors that have recurred following radiation.3 Radiation may be contraindicated for certain tumors because of ill-defined borders, those with tumors on the lower legs, feet, hands or genitalia and for patients with tumors arising in previously irradiated areas. Side effects, as with any treatment, may be intolerable for certain patients.5
Recently, a new class of medications known as hedgehog pathway inhibitors has been developed for the treatment of locally advanced and metastatic BCC. The first-in-class drug, vismodegib (Erivedge, Genentech) received FDA approval in January 2012.3 These oral agents are targeted to treat the underlying mutation found in close to 100% of all BCCs. As experience with their use increases, data on safety, efficacy and tolerability have begun to emerge.
Treatment Considerations
The decision for the best treatment option for patients with advanced BCC is complicated, and must incorporate both tumor and patient characteristics as well as prior treatment history. In several cases, more than one therapeutic modality may be appropriate and multidisciplinary input can be helpful.
For example, large, extensive tumors or those involving the vital structures of the face may be excised by Mohs surgeons under general anesthesia in conjunction with head and neck surgery or surgical oncology. Once clear margins are achieved, the patient can then undergo the appropriate reconstruction.
Often, tumors become advanced because of patient neglect and fear of medical care. In these patients, a discussion of extensive surgery or the associated high facility costs and recovery time involved may deter them from pursuing treatment for their advanced BCC. These patients may be better served with radiation or hedgehog inhibitors. Furthermore, nursing home patients with advanced degenerative disease and low functional status may also be good candidates for these medicines.
When developing a treatment plan, consider the characteristics of the BCC and the effects of therapy:
• Size
• Extent and invasiveness
• Difficult-to-treat location
• Recurrence
• Location
• Non-continuous growth
Surgery may be inappropriate if:
• Substantial deformity or functional loss may result (eg, loss of an ear)
• Patient cannot tolerate surgery
• Clear margins cannot be obtained
• Medical comorbidities prohibit surgery
Radiation may be inappropriate if:
• Radiation has failed previously
• A tumor has recurred following previous radiation
• If excessive radiation dose must be used
• If damage to underlying structures is a concern (eg, the eye)
Oral hedgehog inhibitors may be inappropriate if:
• Adverse effects are intolerable
• Patient’s tumor unsponsive to drug
• Tumor progresses despite treatment
In summary, management of advanced BCC should be individualized for each patient. One must consider functional and cosmetic outcome and tolerability of extensive surgical procedures.
When surgery is possible and clear margins can be achieved, this will give the patient the best chance for a long-term cure of their disease. In all situations, surgery should be considered first.
When surgery is not an option for factors related to the patient or to the cancer being treated, or if tumors have recurred following surgery, alternative treatment modalities such as radiation or oral hedgehog inhibitors may be considered.
Dr. Ibrahim is an assistant professor in dermatology, Division of Dermatologic Surgery, Wilmot Cancer Center at University of Rochester in Rochester, NY.
Disclosure: Dr. Ibrahim is a consultant and speaker for Genentech.
References
1. Caro I, Low J. The Role of the Hedgehog Signaling Pathway in the Development of Basal Cell Carcinoma and Opportunities for Treatment. Clinical Cancer Research. 2010;16:3335-3339.
2. Rubin AL, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262-2269.
3. Bader RS. Basal cell carcinoma treatment & management. Medscape. https://emedicine.medscape.com/article/276624-treatment#aw2aab6b6b4. Accessed January 21, 2014.
4. Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004;23(3-4):389-402.
5. Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol. 2007;4(8):462-469.
Basal cell carcinoma (BCC) is the most common human malignancy1 and by far the most prevalent form of skin cancer, accounting for over 80% of all cases.2 The typical BCC is a slow-growing tumor that is treatable by a variety of treatment modalities. Common in elderly, fair-skinned individuals,3 this disease occurs largely in sun-exposed areas of the body and is felt to be a result of chronic ultraviolet exposure.2
Treatment of BCC is fairly straightforward, with surgical, destructive and topical treatment options available.2 This results in a 5-year cure rate of over 90%.2 In certain cases, however, neglected, aggressive or recurrent BCC can progress to an advanced state.4 In extremely rare cases, BCC may metastasize to other anatomic locations, carrying a poor prognosis.4
The tumor characteristics that define a given cancer as being an advanced BCC can vary. When defining advanced BCC, there are certain features that render cancers challenging to treat. These include large size, extent and invasiveness of disease and difficult-to-treat locations (ie, ear canal or medial canthus).3
For example a 10-cm BCC on the back would be relatively straightforward to treat surgically, however, this tumor on the ear or invading deeply into the bones of the skull would pose significant therapeutic challenges. Likewise, a 1-cm tumor located on the medial canthus and extending on to both eyelids and the conjunctival surface of the eye is not a big tumor, but surgery may have to involve enucleation.4 No absolute definition exists of what qualifies a BCC as being advanced, and this is a decision made by the treating physicians.
Recurrent tumors can be more difficult to treat, as they are often multifocal in nature and cure rates of standard approaches, such as Mohs micrographic surgery, can be decreased. Patients with certain genetic conditions may exhibit a strong predisposition to the development of numerous aggressive BCCs that may develop to an advanced state. Among the most common of these conditions are basal cell nevus syndrome, xeroderma pigmentosum and oculocutaneous albinism.
Lastly, certain patient characteristics may also make standard surgical approaches challenging, limiting treatment options. This may include patients of advanced age, those with multiple comorbidities or of low functional status.5
Advanced BCC
When considering treatment options for advanced BCC, choices are limited. In these situations, less invasive options such as electrodesiccation, curettage, cryosurgery, photodynamic therapy or topical agents would not be effective.
When surgery is an option, this remains the gold standard for achieving the highest cure rate and should always be considered as first-line treatment. However, patients may not be ideal surgical candidates if they are unable to tolerate surgery or if surgery is so extensive that it would result in significant deformity or loss of function (eg, loss of an ear or an eye). See Figure 1 for potential treatment algorithm for advanced BCC.
Radiation therapy has been utilized for decades in a variety of tumors, and may be an option for certain advanced BCCs. Typically, radiation is delivered in fractions 5 days per week over several weeks. Radiation may be inappropriate in patients who cannot tolerate this dosing schedule, or who have failed prior radiation treatment or in tumors that have recurred following radiation.3 Radiation may be contraindicated for certain tumors because of ill-defined borders, those with tumors on the lower legs, feet, hands or genitalia and for patients with tumors arising in previously irradiated areas. Side effects, as with any treatment, may be intolerable for certain patients.5
Recently, a new class of medications known as hedgehog pathway inhibitors has been developed for the treatment of locally advanced and metastatic BCC. The first-in-class drug, vismodegib (Erivedge, Genentech) received FDA approval in January 2012.3 These oral agents are targeted to treat the underlying mutation found in close to 100% of all BCCs. As experience with their use increases, data on safety, efficacy and tolerability have begun to emerge.
Treatment Considerations
The decision for the best treatment option for patients with advanced BCC is complicated, and must incorporate both tumor and patient characteristics as well as prior treatment history. In several cases, more than one therapeutic modality may be appropriate and multidisciplinary input can be helpful.
For example, large, extensive tumors or those involving the vital structures of the face may be excised by Mohs surgeons under general anesthesia in conjunction with head and neck surgery or surgical oncology. Once clear margins are achieved, the patient can then undergo the appropriate reconstruction.
Often, tumors become advanced because of patient neglect and fear of medical care. In these patients, a discussion of extensive surgery or the associated high facility costs and recovery time involved may deter them from pursuing treatment for their advanced BCC. These patients may be better served with radiation or hedgehog inhibitors. Furthermore, nursing home patients with advanced degenerative disease and low functional status may also be good candidates for these medicines.
When developing a treatment plan, consider the characteristics of the BCC and the effects of therapy:
• Size
• Extent and invasiveness
• Difficult-to-treat location
• Recurrence
• Location
• Non-continuous growth
Surgery may be inappropriate if:
• Substantial deformity or functional loss may result (eg, loss of an ear)
• Patient cannot tolerate surgery
• Clear margins cannot be obtained
• Medical comorbidities prohibit surgery
Radiation may be inappropriate if:
• Radiation has failed previously
• A tumor has recurred following previous radiation
• If excessive radiation dose must be used
• If damage to underlying structures is a concern (eg, the eye)
Oral hedgehog inhibitors may be inappropriate if:
• Adverse effects are intolerable
• Patient’s tumor unsponsive to drug
• Tumor progresses despite treatment
In summary, management of advanced BCC should be individualized for each patient. One must consider functional and cosmetic outcome and tolerability of extensive surgical procedures.
When surgery is possible and clear margins can be achieved, this will give the patient the best chance for a long-term cure of their disease. In all situations, surgery should be considered first.
When surgery is not an option for factors related to the patient or to the cancer being treated, or if tumors have recurred following surgery, alternative treatment modalities such as radiation or oral hedgehog inhibitors may be considered.
Dr. Ibrahim is an assistant professor in dermatology, Division of Dermatologic Surgery, Wilmot Cancer Center at University of Rochester in Rochester, NY.
Disclosure: Dr. Ibrahim is a consultant and speaker for Genentech.
References
1. Caro I, Low J. The Role of the Hedgehog Signaling Pathway in the Development of Basal Cell Carcinoma and Opportunities for Treatment. Clinical Cancer Research. 2010;16:3335-3339.
2. Rubin AL, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262-2269.
3. Bader RS. Basal cell carcinoma treatment & management. Medscape. https://emedicine.medscape.com/article/276624-treatment#aw2aab6b6b4. Accessed January 21, 2014.
4. Walling HW, Fosko SW, Geraminejad PA, Whitaker DC, Arpey CJ. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev. 2004;23(3-4):389-402.
5. Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nat Clin Pract Oncol. 2007;4(8):462-469.
