Sequencing Hedgehog Inhibitors with Surgery, Radiation, and Immunotherapy in BCC

In "Sequencing Hedgehog Inhibitors with Surgery, Radiation, and Immunotherapy in BCC," Dr. Singh turns to how oral hedgehog inhibition can be combined with other treatment modalities.

Dr. Singh begins with a caution. The labeled indication for hedgehog inhibitors covers patients who are not candidates for curative surgery or curative radiation. Even so, in his practice the team often uses hedgehog inhibitor therapy before surgery to shrink the tumor in advance.

He outlines the benefits of this neoadjuvant approach. When the tumor is reduced before definitive treatment, the treated area is smaller. Patients are left with a smaller scar, which he links directly to patient satisfaction.

For high-risk tumors, including those with large size, deep invasion, or an immunocompromised host, adjuvant radiation after surgery may also be appropriate. Dr. Singh believes neoadjuvant use of hedgehog inhibitors is underused largely because of how care is structured. Patients typically receive a biopsy and diagnosis from a dermatologist, then are scheduled directly for excision.

Within a multidisciplinary group, he explains, there is time to build a plan that may combine oral therapy, surgery, and radiation where indicated. The aim is the best possible cure rate alongside the greatest patient satisfaction. Patient preference remains central in both directions, because some patients refuse surgery while others will not accept oral hedgehog therapy under any circumstances.

Immunotherapy is another option. Dr. Singh notes that many patients receive PD-1 or PD-L1 inhibitors for their skin cancers, most often when a hedgehog inhibitor is contraindicated or has already failed. He sets the details of immunotherapy aside for this program.

He highlights a practical advantage of hedgehog inhibitors. As oral agents, they avoid the infusion centers and specialized care that immunotherapy typically requires, which may not be available within every patient's geographic reach. Finally, he emphasizes that agents in this class are not identical. Differences in pharmacokinetics, dosing, and administration can affect whether an individual patient achieves a complete or partial response.

In "Differentiating the Two Approved Hedgehog Inhibitors in BCC," Dr. Singh will compare dosing, drug holidays, and the pharmacokinetic differences between the two approved agents.