Nonsurgical Therapies for Non-Melanoma Skin Cancers

• Radiation therapy:
  • Is often reserved for:
    • Patients unable or unwilling to undergo surgical treatment of primary lesions or
    • When clear margins cannot be obtained by Mohs or more extensive surgery
  • It is also widely accepted as adjuvant treatment of recurrent or histologically aggressive tumors:
    • Particularly those with perineural invasion
  • For high-grade NMSC with perineural involvement or invasion into bone:
    • Radiation therapy is generally recommended in conjunction with surgical excision
  • Radiation therapy can be further used as:
    • Adjuvant or palliative treatment for lymph node metastases
  • Disadvantages of radiation therapy include:
    • Acute and chronic radiation changes:
      • Dyspigmentation
      • Telangiectasia
      • Radiodystrophy
    • Higher recurrence rates in BCC
    • Lack of margin control
    • Increased number of treatment sessions
  • As radiation therapy can result in NMSC decades after exposure:
    • It should be used cautiously in young patients
  • It is also contraindicated in nevoid BCC
• Topical therapies for superficial NMSC and AKs include:
  • 5% fluorouracil (5-FU)
  • Imiquimod creams
• 5-FU:
  • Is an antineoplastic antimetabolite
• Imiquimod:
  • Is a synthetic immune response modifier:
    • That enhances cell-mediated immune response:
      • Via the induction of proinflammatory cytokines
• These topical therapies are most commonly used for:
  • AKs as well as for superficial BCCs and SCCs in situ when surgery or other treatment techniques are contraindicated or impractical
• Topical 5-FU is not appropriate for:
  • Nodular BCC
  • It is not recommended for SCC due to high recurrence rates
• Treatment regimens for AKs with 5-FU vary widely:
  • In general, 5-FU is applied to the affected area once or twice daily for a period ranging from 2 to 6 weeks:
    • Retreatment several months later:
      • Either with cryotherapy or other modalities, may be necessary
• For the treatment of superficial BCC:
  • 5-FU can be applied daily to the tumor and several millimeters of surrounding skin for a period of at least 4 weeks:
    • After a 2- to 3-week after the treatment ended:
      • The area is then evaluated clinically for residual tumor
      • Biopsy is often indicated to ensure adequate therapy
    • Significant erythema, stinging, oozing, and crusting are often reported:
      • Especially with more aggressive treatment regimens
• 5-FU:
  • Can be applied to an entire region, such as the face, chest, arms, or hands
• Imiquimod therapy:
  • Is approved for the treatment of AKs and superficial BCC but should not be used for SCC
  • In general, less local skin reaction is reported compared to 5-FU
  • For AKs the cream is applied:
    • Two nonconsecutive days a week for 16 weeks
  • For superficial BCC:
    • The cream should be applied 5 nights a week for at least 6 weeks
    • After a 2- to 3-month respite, the lesion is evaluated either clinically or histologically (rebiopsy) to confirm adequate therapy
  • While imiquimod can also be used for nodular BCC:
    • The treatment duration requires 12 weeks:
      • The response is lower (76%) compared to a greater than 85% success rate for superficial BCC
  • Imiquimod is often well tolerated:
    • Causes minimal or no scarring, and is particularly useful for multiple lesions concentrated in one area
• Photodynamic therapy (PDT):
  • Is another noninvasive method used for the treatment of AKs and superficial BCC
  • A photosensitizer (most commonly, aminolevulinic acid) is applied to the skin and activated with a light source
  • The tumor cells retain the photosensitizer for longer periods of time than normal cells:
    • Resulting in preferential killing
  • Cure rates for AKs are reported to be as high as 90%:
    • However, recurrence rates at 5 years for superficial and nodular BCC have been reported to be as high as 14% to 22% respectively
  • Side effects include:
    • Burning or stinging pain during the treatment and posttreatment periods
    • Erythema, swelling, and temporary hyper- or hypopigmentation
    • But overall the cosmetic results are superior in comparison to surgery or cryotherapy
  • Systemic PDT:
    • Has also been tested as a treatment for BCC and may be appropriate for individuals presenting with multiple lesions or nevoid BCC syndrome
• Chemoprevention:
  • With low-dose oral retinoids has shown some promise in the prevention of SCC for chronically immunosuppressed patients who have undergone organ transplantation:
    • However, long-term therapy is needed as beneficial effects are often lost when these drugs are discontinued

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