Basal Cell Carcinoma: Prevention, Management, and Challenging Case Strategies

Conclusions

• Basal cell carcinoma is common, rising in incidence, and should be managed as a chronic disease with ongoing surveillance because patients frequently develop additional skin cancers and may also have increased melanoma risk.
• UVB-induced DNA damage and dysregulation of the Hedgehog pathway are central to BCC pathogenesis, with PTCH1 alterations being especially common in sporadic disease.
• Prevention should begin early, since interventions such as nicotinamide appear most useful when started after the first skin cancer rather than after many recurrent tumors.
• Nicotinamide 500 mg twice daily can reduce new nonmelanoma skin cancers during treatment, with modest benefit for BCC and no clear persistent effect after stopping.
• There is no meaningful cardiovascular harm signal for nicotinamide at standard doses, supporting its use in appropriate high-risk patients.
• Topical or field-directed chemoprevention is more effective for squamous cell carcinoma prevention than for basal cell carcinoma, so expectations for BCC benefit should be modest.
• Mohs surgery remains the gold standard for high-risk BCC because it offers the lowest recurrence rates, but treatment choice should be individualized rather than automatically maximized for every patient.
• Radiation, cryosurgery, ED&C, and standard excision can be reasonable alternatives when surgery is not ideal, especially for patients who are frail, older, or prefer less invasive care.
• Photodynamic therapy can be a useful non-surgical option for superficial or low-risk BCC and may help shrink tumors before surgery, but it is less reliable for thicker or infiltrative lesions.
• Vitamin D may enhance PDT response, suggesting that optimizing patient biology may improve outcomes in noninvasive treatment strategies.
• Vismodegib and sonidegib are important for locally advanced or metastatic BCC, but their adverse effects limit long-term tolerability and cause frequent discontinuation.
• Patidegib may become a useful preventive or suppressive therapy, especially in Gorlin syndrome, but current results are not strong enough to call it a cure for established BCC.
• Checkpoint blockade is emerging as a promising later-line or even earlier-line strategy for advanced BCC, and intralesional approaches may expand the therapeutic toolkit.
• The most effective BCC management depends on matching treatment intensity to disease risk, lesion subtype, patient frailty, and patient goals rather than pursuing a one-size-fits-all cure rate.
• Regular follow-up, careful re-biopsy of suspicious changes, and willingness to adjust the plan are essential for patients with recurrent, extensive, or hard-to-treat BCC.