Why Hedgehog Inhibitors Remain Underused in Advanced BCC

: "Why Hedgehog Inhibitors Remain Underused in Advanced BCC" takes up the question of why oral systemic therapy is often overlooked for patients with advanced basal cell carcinoma.

Dr. Singh describes hedgehog pathway inhibitors as a frequent first-line option for patients with locally advanced basal cell carcinoma. Speaking as a Mohs surgeon, he nonetheless believes the class is underutilized, in part because so many of these tumors are surgically curable.

In his view, the most important indication for considering systemic therapy is patient preference. He regularly sees patients who have undergone Mohs surgery many times for multiple skin cancers over the years. He describes this as surgical fatigue, and these patients begin asking whether excision is truly the only path forward.

Dr. Singh listens for specific cues during preoperative visits. Questions about whether the cancer could simply be monitored, or what would happen if it were left alone, prompt him to raise hedgehog inhibitor therapy. These conversations can lead to an oral treatment discussion even when the tumor did not initially appear to warrant systemic therapy. For that reason, he argues systemic options should be considered earlier than they currently are for many patients.

He then reviews the two approved agents. Vismodegib is indicated for metastatic basal cell carcinoma, or for locally advanced disease that has recurred after surgery or occurs in patients who are not candidates for surgery or radiation. Sonidegib is indicated for adults with locally advanced disease that has recurred after surgery or radiation, or who are not candidates for either.

Dr. Singh acknowledges that surgical and radiation candidacy are themselves open to interpretation. At City of Hope, he, the radiation oncologist, and the medical oncologist can meet with a patient together in real time. That model lets the team weigh the tumor, the labeled indications, and the patient's overall goals of care rather than defaulting automatically to surgery or radiation.

Up next, in "Sequencing Hedgehog Inhibitors with Surgery, Radiation, and Immunotherapy in BCC," Dr. Singh examines how hedgehog inhibitors can be combined and sequenced with surgery, radiation, and immunotherapy.