Pathological Insights into the Limitations of Clinical and Dermoscopic Evaluations in Monitoring Sonidegib Treatment Response for Locally Advanced Basal Cell Carcinoma: A Real-World Study

Abstract Introduction Surgical excision is the standard treatment for basal cell carcinoma (BCC). For locally advanced BCC (laBCC) not suitable for surgery or radiotherapy, Hedgehog pathway inhibitors (HHIs) such as sonidegib are important options. Clinical observations have shown that sonidegib may lead to pigmentation and scarring, which can affect treatment evaluation. We evaluated the efficacy and safety of sonidegib in Chinese patients with laBCC and examined discrepancies between clinical/dermoscopic assessments and pathological findings, including posttreatment pathological changes. Methods This single-center retrospective study included 54 patients with laBCC treated with sonidegib 200 mg/day for ≥ 3 months (October 2022–July 2025). Response assessment integrated VISIA-based planimetric lesion-area regression, standardized dermoscopy, and dermoscopy-guided multi-site biopsy as the pathological gold standard. The primary endpoint was objective response rate (ORR); secondary endpoints included disease control rate (DCR) and safety. Results At 3 months, ORR was 87% (complete response [CR] 48%; partial response [PR] 39%), and DCR was 100%. Pathology showed complete clearance in 48.1% and residual tumor in 51.9%, with six cases showing apparent histologic subtype shifts. Dermoscopy in patients with complete remission still demonstrated a high false-positive rate (branching blood vessels 53.8%, blue-gray dots 61.5%), leading to decreased diagnostic specificity. Adverse events occurred in 81.5% of patients; 70.4% reported multiple events, most commonly muscle cramps (66.7%), dysgeusia (59.3%), and alopecia (55.6%). All events were grade 1–3, and no patient discontinued treatment as a result of toxicity. Conclusion In this real-world Chinese laBCC cohort, sonidegib produced a clinically meaningful response with a favorable safety profile. However, clinical and dermoscopic assessments showed substantial false positives due to posttreatment changes; pathological biopsy remains essential to confirm tumor clearance. Advanced noninvasive imaging (e.g., reflectance confocal microscopy) may further improve monitoring. Prospective studies with longer follow-up are warranted.