Dermatology Times has published new guidance on how to sequence hedgehog pathway inhibitors (HHIs) alongside surgery, radiation therapy and immunotherapy in the management of basal cell carcinoma (BCC). The discussion targets one of the most persistent practical questions in skin cancer care: when a patient qualifies for several modalities, in what order should clinicians deploy them?

Why sequencing matters in BCC

Surgery remains the definitive treatment for most localized BCC, but locally advanced and metastatic disease frequently demands systemic therapy. Hedgehog inhibitors — vismodegib and sonidegib — were the first systemic agents approved for advanced BCC, and the arrival of PD-1 immunotherapy has since added a second systemic option for patients who cannot tolerate or fail HHI treatment.

That abundance creates the sequencing problem. Neoadjuvant HHI before surgery can shrink tumors and make previously unresectable lesions operable. Radiation can be combined with, or follow, systemic therapy. Immunotherapy typically enters later, after HHI intolerance or progression. The Dermatology Times piece walks through these decision points.

What does the guidance address?

The publication covers several core clinical questions:

• When to use hedgehog inhibitors neoadjuvantly to downstage tumors before surgical resection
• How to position radiation relative to systemic therapy in patients who are not surgical candidates
• When to switch from HHI to immunotherapy after progression or unacceptable adverse events
• How to manage patients whose tumors recur after multimodal treatment

Hedgehog inhibitor therapy carries a well-characterized adverse event profile — muscle spasms, alopecia, dysgeusia and fatigue among the most common — and these tolerability issues often drive treatment breaks and sequencing decisions as much as tumor response does.

The clinical backdrop

BCC is the most common skin cancer, and while the vast majority of cases are cured with surgery or topical therapy, a subset progresses to locally advanced or metastatic disease. For that subset, treatment historically offered few options until HHI approval changed the therapeutic landscape roughly a decade ago, and checkpoint inhibition expanded it again.

Accurate staging and multidisciplinary input — dermatology, surgical oncology, radiation oncology and medical oncology — anchor the sequencing decisions the article describes. Tumor location, size, depth of invasion and prior treatments all shape whether a clinician starts with an HHI, proceeds directly to surgery, or refers for radiation.

The road ahead

As experience with combined and sequential approaches grows, clinicians can expect clearer frameworks for matching BCC patients to the right order of surgery, radiation, hedgehog inhibition and immunotherapy — the central aim of the Dermatology Times guidance.